%0 journal article %@ 2190-4979 %A García-Pereira, F.,González-Rouco, J.F.,Melo-Aguilar, C.,Steinert, N.J.,García-Bustamante, E.,de Vrese, P.,Jungclaus, J.,Lorenz, S.,Hagemann, S.,Cuesta-Valero, F.J.,García-García, A.,Beltrami, H. %D 2024 %J Earth System Dynamics %N 3 %P 547-564 %R doi:10.5194/esd-15-547-2024 %T First comprehensive assessment of industrial-era land heat uptake from multiple sources %U https://doi.org/10.5194/esd-15-547-2024 3 %X The anthropogenically intensified greenhouse effect has caused a radiative imbalance at the top of the atmosphere during the industrial period. This, in turn, has led to an energy surplus in various components of the Earth system, with the ocean storing the largest part. The land contribution ranks second with the latest observational estimates based on borehole temperature profiles, which quantify the terrestrial energy surplus to be 6 % in the last 5 decades, whereas studies based on state-of-the-art climate models scale it down to 2 %. This underestimation stems from land surface models (LSMs) having a subsurface that is too shallow, which severely constrains the land heat uptake simulated by Earth system models (ESMs). A forced simulation of the last 2000 years with the Max Planck Institute ESM (MPI-ESM) using a deep LSM captures 4 times more heat than the standard shallow MPI-ESM simulations in the historical period, well above the estimates provided by other ESMs. However, deepening the LSM does not remarkably affect the simulated surface temperature. It is shown that the heat stored during the historical period by an ESM using a deep LSM component can be accurately estimated by considering the surface temperatures simulated by the ESM using a shallow LSM and propagating them with a standalone forward model. This result is used to derive estimates of land heat uptake using all available observational datasets, reanalysis products, and state-of-the-art ESM experiments. This approach yields values of 10.5–16.0 ZJ for 1971–2018, which are 12 %–42 % smaller than the latest borehole-based estimates (18.2 ZJ). %0 journal article %@ 1866-3508 %A Stevens, B.,Adami, S.,Ali, T.,Anzt, H.,Aslan, Z.,Attinger, S.,Bäck, J.,Baehr, J.,Bauer, P.,Bernier, N.,Bishop, B.,Bockelmann, H.,Bony, S.,Brasseur, G.,Bresch, D. N.,Breyer, S.,Brunet, G.,Buttigieg, P. L.,Cao, J.,Castet, C.,Cheng, Y.,Dey Choudhury, A.,Coen, D.,Crewell, S.,Dabholkar, A.,Dai, Q.,Doblas-Reyes, F.,Durran, D.,El Gaidi, A.,Ewen, C.,Exarchou, E.,Eyring, V.,Falkinhoff, F.,Farrell, D.,Forster, P. M.,Frassoni, A.,Frauen, C.,Fuhrer, O.,Gani, S.,Gerber, E.,Goldfarb, D.,Grieger, J.,Gruber, N.,Hazeleger, W.,Herken, R.,Hewitt, C.,Hoefler, T.,Hsu, H. H.,Jacob, D.,Jahn, A.,Jakob, C.,Jung, T.,Kadow, C.,Kang, I. S.,Kang, S.,Kashinath, K.,Kleinen-von Königslöw, K.,Klocke, D.,Kloenne, U.,Klöwer, M.,Kodama, C.,Kollet, S.,Kölling, T.,Kontkanen, J.,Kopp, S.,Koran, M.,Kulmala, M.,Lappalainen, H.,Latifi, F.,Lawrence, B.,Lee, J. Y.,Lejeun, Q.,Lessig, C.,Li, C.,Lippert, T.,Luterbacher, J.,Manninen, P.,Marotzke, J.,Matsouoka, S.,Merchant, C.,Messmer, P.,Michel, G.,Michielsen, K.,Miyakawa, T.,Müller, J.,Munir, R.,Narayanasetti, S.,Ndiaye, O.,Nobre, C.,Oberg, A.,Oki, R.,Özkan-Haller, T.,Palmer, T.,Posey, S.,Prein, A.,Primus, O.,Pritchard, M.,Pullen, J.,Putrasahan, D.,Quaas, J.,Raghavan, K.,Ramaswamy, V.,Rapp, M.,Rauser, F.,Reichstein, M.,Revi, A.,Saluja, S.,Satoh, M.,Schemann, V.,Schemm, S.,Schnadt Poberaj, C.,Schulthess, T.,Senior, C.,Shukla, J.,Singh, M.,Slingo, J.,Sobel, A.,Solman, S.,Spitzer, J.,Stier, P.,Stocker, T.,Strock, S.,Su, H.,Taalas, P.,Taylor, J.,Tegtmeier, S.,Teutsch, G.,Tompkins, A.,Ulbrich, U.,Vidale, P. L.,Wu, C. M.,Xu, H.,Zaki, N.,Zanna, L.,Zhou, T.,Ziemen, F. %D 2024 %J Earth System Science Data %N 4 %P 2113–2122 %R doi:10.5194/essd-16-2113-2024 %T Earth Virtualization Engines (EVE) %U https://doi.org/10.5194/essd-16-2113-2024 4 %X To manage Earth in the Anthropocene, new tools, new institutions, and new forms of international cooperation will be required. Earth Virtualization Engines is proposed as an international federation of centers of excellence to empower all people to respond to the immense and urgent challenges posed by climate change. %0 journal article %@ 1044-5803 %A Jungbluth, J.,Bruns, S.,Schmidt, C.,Beckmann, F.,Moosmann, J.,Gapeeva, A.,Carstensen, J.,Adelung, R.,Zeller-Plumhoff, B.,Gurka, M. %D 2023 %J Materials Characterization %N %P 113345 %R doi:10.1016/j.matchar.2023.113345 %T Interface failure analysis of embedded NiTi SMA wires using in situ high-resolution X-ray synchrotron tomography %U https://doi.org/10.1016/j.matchar.2023.113345 %X High-resolution X-ray in situ pull-out tests with stepwise increasing load were performed to investigate the force transfer between a NiTi shape memory alloy (SMA) wire with selectively electrochemically structured surface and the surrounding epoxy polymer matrix. The advancing interfacial failure was observed. Furthermore, the stochastic surface structure of the SMA wire was utilized to determine the axial and radial strains introduced into the SMA wire during the test by performing digital volume correlation on the reconstructed microcomputed tomography (μCT) data. Thus, the global and local strain of the embedded SMA wire volume could be correlated with the force of the first interfacial failure. Using image segmentation on the cross-sections derived from the reconstructed μCT volume data, it was possible to quantitatively assess the growth of the amount of delamination along the observed length of the embedded SMA wire for increasing load levels. In addition, the advancing interfacial failure was correlated with changes in the cross-sectional area of the SMA wire due to transverse contraction. Finally, the local surface strain characteristics of an embedded SMA wire during μCT of an in situ pull-out test were compared to a non-embedded SMA wire loaded in situ. It was found that the polymer matrix exerts an external stress on the SMA wire, constraining its radial strain. Thereby, the study reveals that interfacial failure is not only a shear-stress-induced failure. %0 journal article %@ 1748-9326 %A Essell, H.,Krusic, P.,Esper, J.,Wagner, S.,Braconnot, P.,Jungclaus, J.,Muschitiello, F.,Oppenheimer, C.,Büntgen, U. %D 2023 %J Environmental Research Letters %N 11 %P 114022 %R doi:10.1088/1748-9326/ad0065 %T A frequency-optimised temperature record for the Holocene %U https://doi.org/10.1088/1748-9326/ad0065 11 %X Existing global mean surface temperature reconstructions for the Holocene lack high-frequency variability that is essential for contextualising recent trends and extremes in the Earth's climate system. Here, we isolate and recombine archive-specific climate signals to generate a frequency-optimised record of interannual to multi-millennial temperature changes for the past 12 000 years. Average temperatures before ∼8000 years BP and after ∼4000 years BP were 0.26 (±2.84) °C and 0.07 (±2.11) °C cooler than the long-term mean (0–12 000 years BP), while the Holocene Climate Optimum ∼7000–4000 years BP was 0.40 (±1.86) °C warmer. Biased towards Northern Hemisphere summer temperatures, our multi-proxy record captures the spectral properties of transient Earth system model simulations for the same spatial and season domain. The new frequency-optimised trajectory emphasises the importance and complex interplay of natural climate forcing factors throughout the Holocene, with an approximation of the full range of past temperature changes providing novel insights for policymakers addressing the risks of recent anthropogenic warming. %0 journal article %@ 2198-3844 %A Choi, H.,Seo, S.,Yoon, C.J.,Ahn, J.B.,Kim, C.S.,Jung, Y,Kim, Y.,Toma, F.M.,Kim, H.,Lee, S. %D 2023 %J Advanced Science %N 33 %P 2303106 %R doi:10.1002/advs.202303106 %T Organometal Halide Perovskite-Based Photoelectrochemical Module Systems for Scalable Unassisted Solar Water Splitting %U https://doi.org/10.1002/advs.202303106 33 %X Despite achievements in the remarkable photoelectrochemical (PEC) performance of photoelectrodes based on organometal halide perovskites (OHPs), the scaling up of small-scale OHP-based PEC systems to large-scale systems remains a great challenge for their practical application in solar water splitting. Significant resistive losses and intrinsic defects are major obstacles to the scaling up of OHP-based PEC systems, leading to the PEC performance degradation of large-scale OHP photoelectrodes. Herein, a scalable design of the OHP-based PEC systems by modularization of the optimized OHP photoelectrodes exhibiting a high solar-to-hydrogen conversion efficiency of 10.4% is suggested. As a proof-of-concept, the OHP-based PEC module achieves an optimal PEC performance by avoiding major obstacles in the scaling up of the OHP photoelectrodes. The constructed OHP module is composed of a total of 16 OHP photoelectrodes, and a photocurrent of 11.52 mA is achieved under natural sunlight without external bias. The successful operation of unassisted solar water splitting using the OHP module without external bias can provide insights into the design of scalable OHP-based PEC systems for future practical application and commercialization. %0 journal article %@ 1614-6840 %A Choi, H.,Kim, Y.Y.,Seo, S.,Jung, Y.,Yoo, S.M.,Moon, C.S.,Jeon, N.J.,Lee, S.,Lee, K.,Toma, F.M.,Seo, J. %D 2023 %J Advanced Energy Materials %N 31 %P 2300951 %R doi:10.1002/aenm.202300951 %T Suppression of undesired losses in organometal halide perovskite-based photoanodes for efficient photoelectrochemical water splitting %U https://doi.org/10.1002/aenm.202300951 31 %X Organometal halide perovskites (OHPs) have become potential candidates for high-efficiency photoelectrodes for use in photoelectrochemical (PEC) water splitting. However, undesired losses, such as the non-radiative recombination of photogenerated carriers and sluggish reaction kinetics of PEC water splitting, are the main limitations to achieving maximum efficiency for OHP-based photoelectrodes. Herein, high-efficiency OHP-based photoanodes with a rational design that suppresses the undesired losses is reported. As a rational design for OHP-based photoanodes, the defect-passivated electron transport layers effectively suppress the undesired recombination of photogenerated carriers from the OHP layers. In addition, Fe-doped Ni3S2 with a high catalytic activity promotes the reaction kinetics of PEC water oxidation, thereby suppressing the undesired losses at the interface between the OHP photoanodes and electrolytes. The fabricated Fe-doped Ni3S2/Ni foil/OHP photoanodes exhibit a remarkable applied bias photon-to-current efficiency of 12.79%, which is the highest of the previously reported OHP-based photoanodes by suppressing undesired losses. The strategies for achieving high-efficiency OHP-based photoanodes provide insights into the rational design of photoelectrodes based on OHPs. %0 journal article %@ 0925-8388 %A Kim, H.,Shin, S.,Jung, D.,Kim, J. %D 2023 %J Journal of Alloys and Compounds %N %P 168743 %R doi:10.1016/j.jallcom.2023.168743 %T Fabrication of Si/N-doped carbon nanotube composite via spray drying followed by catalytic chemical vapor deposition %U https://doi.org/10.1016/j.jallcom.2023.168743 %X Developing an effective structure for the silicon-carbon composite that promotes electric-ionic conductivity and reduces the volume change is a key issue for Si-based anode. In this study, spherical granules comprising silicon nanoparticles (Si-NPs) grafted with nitrogen-doped carbon nanotubes (Si-NCNTs) are fabricated via spray drying followed by catalytic chemical vapor deposition (CCVD). The initial discharge and charge capacities of the Si-NCNTs are 2457 and 1820 mA h g−1, respectively. The Si-NCNTs shows a capacity retention of 57% after 200 cycles as well as improved rate capability when compared to the Si-NPs and commercial CNTs composites (Si-CNTs) fabricated via spray drying alone. The Li+ ion-diffusion-coefficient (DLi+) of the Si-NCNTs is approximately ∼three times larger than that of the Si-CNTs at critical lithiation potential. The NCNTs that form the interconnections between Si-NPs play the role of electrically conductive buffers that could accommodate the volume change produced and favor Li+ ion transport. %0 conference lecture %@ %A Held, M.,Eschke, C.,Kirchner, F.,Meller, M.,Sahim, S.,Jung, N.,Garabedian, N.,Bagov, I.,Greiner, C.,Bock, F.,Klusemann, B.,Wieland, F.,Fried, T.,Aydin, R.,Isensee, F. %D 2023 %J Microscopy Conference 2023 %N %P %T Electronic Lab Notebooks compiling Big Datasets for Machine Learning Analysis %U %X %0 journal article %@ 1386-0291 %A Lau, S.,Gossen, M.,Lendlein, A.,Jung, F. %D 2022 %J Clinical Hemorheology and Microcirculation %N 3 %P 191-203 %R doi:10.3233/CH-211294 %T Differential sensitivity of assays for determining vein endothelial cell senescence %U https://doi.org/10.3233/CH-211294 3 %X In vivo endothelialization of polymer-based cardiovascular implant materials is a promising strategy to reduce the risk of platelet adherence and the subsequent thrombus formation and implant failure. However, endothelial cells from elderly patients are likely to exhibit a senescent phenotype that may counteract endothelialization. The senescence status of cells should therefore be investigated prior to implantation of devices designed to be integrated in the blood vessel wall. Here, human umbilical vein endothelial cells (HUVEC) were cultivated up to passage (P) 4, 10 and 26/27 to determine the population doubling time and the senescence status by four different methods. Determination of the senescence-associated β-galactosidase activity (SA-β-Gal) was carried out by colorimetric staining and microscopy (i), as well as by photometric quantification (ii), and the expression of senescence-associated nuclear proteins p16 and p21 as well as the proliferation marker Ki67 was assessed by immunostaining (iii), and by flow cytometry (iv). The population doubling time of P27-cells was remarkably greater (103±65 h) compared to P4-cells (24±3 h) and P10-cell (37±15 h). Among the four different methods tested, the photometric SA-β-Gal activity assay and the flow cytometric determination of p16 and Ki67 were most effective in discriminating P27-cells from P4- and P10-cells. These methods combined with functional endothelial cell analyses might aid predictions on the performance of implant endothelialization in vivo. %0 journal article %@ 2196-7350 %A Tartivel, L.,Blocki, A.,Braune, S.,Jung, F.,Behl, M.,Lendlein, A. %D 2022 %J Advanced Materials Interfaces %N 6 %P 2101588 %R doi:10.1002/admi.202101588 %T An Inverse Shape-Memory Hydrogel Scaffold Switching Upon Cooling in a Tissue-Tolerated Temperature Range %U https://doi.org/10.1002/admi.202101588 6 %X Tissue reconstruction has an unmet need for soft active scaffolds that enable gentle loading with regeneration-directing bioactive components by soaking up but also provide macroscopic dimensional stability. Here microporous hydrogels capable of an inverse shape-memory effect (iSME) are described, which in contrast to classical shape-memory polymers (SMPs) recover their permanent shape upon cooling. These hydrogels are designed as covalently photo cross-linked polymer networks with oligo(ethylene glycol)-oligo(propylene glycol)-oligo(ethylene glycol) (OEG-OPG-OEG) segments. When heated after deformation, the OEG-OPG-OEG segments form micelles fixing the temporary shape. Upon cooling, the micelles dissociate again, the deformation is reversed and the permanent shape is obtained. Applicability of this iSME is demonstrated by the gentle loading of platelet-rich plasma (PRP) without causing any platelet activation during this process. PRP is highly bioactive and is widely acknowledged for its regenerative effects. Hence, the microporous inverse shape-memory hydrogel (iSMH) with a cooling induced pore-size effect represents a promising candidate scaffold for tissue regeneration for potential usage in minimally invasive surgery applications. %0 journal article %@ 2059-8521 %A Zhou, S.,Xu, X.,Ma, N.,Jung, F.,Lendlein, A. %D 2022 %J MRS Advances %N %P 354-359 %R doi:10.1557/s43580-021-00132-y %T Prediction of the epichlorohydrin derived cytotoxic substances from the eluent of poly(glycerol glycidyl ether) films %U https://doi.org/10.1557/s43580-021-00132-y %X Glycerol-based epoxy networks have great potential for surface functionalization, providing anti-microbial and protein repellant function. However, the synthesis of glycerol glycidyl ether (GGE) monomer often requires excessive epichlorohydrin (ECH). ECH derived organochloride containing byproducts from monomer production maybe present in the eluent of the polymer networks prepared by cationic ring-opening polymerization. Here, the cytotoxicity analysis revealed cell damages in contact with the polyGGE eluent. The occurrence of organochlorides, which was predicted based on the data from high-performance liquid chromatography/electrospray ionization mass spectrometry, as confirmed by a constant chloride level in GGE and polyGGE, and by a specific peak of C–Cl in infrared spectra of GGE. The resulting polyGGE was densely crosslinked, which possibly contribute to the trapping of organochlorides. These results provide a valuable information for exploring the toxins leaching from polyGGE and propose a feasible strategy for minimizing the cytotoxicity via reducing their crosslink density. %0 journal article %@ 2296-7745 %A Rölfer, L.,Elias Ilosvay, X.,Ferse, S.,Jung, J.,Karcher, D.,Kriegl, M.,Nijamdeen, TWGF.,Riechers, M.,Walker, E. %D 2022 %J Frontiers in Marine Science %N %P 893489 %R doi:10.3389/fmars.2022.893489 %T Disentangling Obstacles to Knowledge Co-Production for Early-Career Researchers in the Marine Sciences %U https://doi.org/10.3389/fmars.2022.893489 %X Knowledge co-production involving researchers and non-academic actors is becoming increasingly important for tackling sustainability issues. Coastal and marine social-ecological systems are one example where knowledge co-production is important, yet also particularly challenging due to their unique characteristics. Early-Career Researchers (ECRs) often face specific obstacles when engaging in the process of knowledge co-production. In this perspective paper, we shed light on the particular characteristics of knowledge co-production in marine social-ecological systems and the obstacles ECRs in the marine sciences face. Based on these obstacles, we discuss actions that can be taken at various organizational levels (institutional, community, supervisor, and individual) in order to leverage change towards a more inclusive environment for ECRs engaging in knowledge co-production. We conclude that both bottom-up (individual to institutions) and top-down (institutions to individual) actions are required. However, we emphasize the responsibilities of institutions to create conditions in which the needs of ECRs are met. This will be necessary to adequately support ECRs engaging in knowledge co-production and thus contribute to tackling sustainability challenges in coastal and marine social-ecological systems. %0 journal article %@ 1942-2466 %A Jungclaus, J.H.,Lorenz, S.J.,Schmidt, H.,Brovkin, V.,Brüggemann, N.,Chegini, F.,Crüger, T.,De-Vrese, P.,Gayler, V.,Giorgetta, M.A.,Gutjahr, O.,Haak, H.,Hagemann, S.,Hanke, M.,Ilyina, T.,Korn, P.,Kröger, J.,Linardakis, L.,Mehlmann, C.,Mikolajewicz, U.,Müller, W.A.,Nabel, J.E.M.S.,Notz, D.,Pohlmann, H.,Putrasahan, D.A.,Raddatz, T.,Ramme, L.,Redler, R.,Reick, C.H.,Riddick, T.,Sam, T.,Schneck, R.,Schnur, R.,Schupfner, M.,von Storch, J.-S.,Wachsmann, F.,Wieners, K.-H.,Ziemen, F.,Stevens, B.,Marotzke, J.,Claussen, M. %D 2022 %J Journal of Advances in Modeling Earth Systems : JAMES %N 4 %P e2021MS002813 %R doi:10.1029/2021MS002813 %T The ICON Earth System Model version 1.0 %U https://doi.org/10.1029/2021MS002813 4 %X This work documents the ICON-Earth System Model (ICON-ESM V1.0), the first coupled model based on the ICON (ICOsahedral Non-hydrostatic) framework with its unstructured, icosahedral grid concept. The ICON-A atmosphere uses a nonhydrostatic dynamical core and the ocean model ICON-O builds on the same ICON infrastructure, but applies the Boussinesq and hydrostatic approximation and includes a sea-ice model. The ICON-Land module provides a new framework for the modeling of land processes and the terrestrial carbon cycle. The oceanic carbon cycle and biogeochemistry are represented by the Hamburg Ocean Carbon Cycle module. We describe the tuning and spin-up of a base-line version at a resolution typical for models participating in the Coupled Model Intercomparison Project (CMIP). The performance of ICON-ESM is assessed by means of a set of standard CMIP6 simulations. Achievements are well-balanced top-of-atmosphere radiation, stable key climate quantities in the control simulation, and a good representation of the historical surface temperature evolution. The model has overall biases, which are comparable to those of other CMIP models, but ICON-ESM performs less well than its predecessor, the Max Planck Institute Earth System Model. Problematic biases are diagnosed in ICON-ESM in the vertical cloud distribution and the mean zonal wind field. In the ocean, sub-surface temperature and salinity biases are of concern as is a too strong seasonal cycle of the sea-ice cover in both hemispheres. ICON-ESM V1.0 serves as a basis for further developments that will take advantage of ICON-specific properties such as spatially varying resolution, and configurations at very high resolution. %0 conference paper %@ %A Munch, P.,Ljungkvist, K.,Kronbichler, M. %D 2022 %J High Performance Computing. ISC High Performance 2022. %N %P 133-152 %R doi:10.1007/978-3-031-07312-0_7 %T Efficient Application of Hanging-Node Constraints for Matrix-Free High-Order FEM Computations on CPU and GPU %U https://doi.org/10.1007/978-3-031-07312-0_7 %X This contribution presents an efficient algorithm for resolving hanging-node constraints on the fly for high-order finite-element computations on adaptively refined meshes, using matrix-free implementations. We concentrate on unstructured hex-dominated meshes and on multi-component elements with nodal Lagrange shape functions in at least one of their components. The application of general constraints is split up into two distinct operators, one specialized in the hanging-node part and a generic one for the remaining constraints, such as Dirichlet boundary conditions. The former implements in-face interpolations efficiently by a sequence of 1D interpolations with sum factorization according to the refinement configuration of the cell. We discuss ways to efficiently encode and decode such refinement configurations. Furthermore, we present distinct differences in the interpolation step on GPU and CPU, as well as compare different vectorization strategies for the latter. Experimental comparisons with a state-of-the-art algorithm that does not exploit the tensor-product structure show that, on CPUs, the additional costs of cells with hanging-node constraints can be reduced by a factor of 5–10 for a Laplace operator evaluation with high-order elements (k≥3) and affine meshes. For non-affine meshes, the costs for the application of hanging-node constraints can be completely hidden behind the memory transfer. The algorithm has been integrated into the open-source finite-element library deal.II. %0 conference lecture %@ %A Lau, S.,Gossen, M.,Lendlein, A.,Jung, F. %D 2022 %J 40. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Differential sensitivity of assays for determining vein endothelial cell senescence %U %X %0 journal article %@ 1525-755X %A González-Rouco, J.,Steinert, N.,García-Bustamante, E.,Hagemann, S.,de Vrese, P.,Jungclaus, J.,Lorenz, S.,Melo-Aguilar, C.,García-Pereira, F.,Navarro, J. %D 2021 %J Journal of Hydrometeorology %N 12 %P 3211-3230 %R doi:10.1175/JHM-D-21-0024.1 %T Increasing the Depth of a Land Surface Model. Part I: Impacts on the Subsurface Thermal Regime and Energy Storage %U https://doi.org/10.1175/JHM-D-21-0024.1 12 %X The representation of the thermal and hydrological states in land surface models is important for a realistic simulation of land–atmosphere coupling processes. The available evidence indicates that the simulation of subsurface thermodynamics in Earth system models is inaccurate due to a zero-heat-flux bottom boundary condition being imposed too close to the surface. To assess the influence of soil model depth on the simulated terrestrial energy and subsurface thermal state, sensitivity experiments have been carried out in piControl, historical, and RCP scenarios. A deeper bottom boundary condition placement has been introduced into the JSBACH land surface model by enlarging the vertical stratification from 5 to 12 layers, thereby expanding its depth from 9.83 to 1416.84 m. The model takes several hundred years to reach an equilibrium state in stand-alone piControl simulations. A depth of 100 m is necessary, and 300 m recommendable, to handle the warming trends in historical and scenario simulations. Using a deep bottom boundary, warming of the soil column is reduced by 0.5 to 1.5 K in scenario simulations over most land areas, with the largest changes occurring in northern high latitudes, consistent with polar amplification. Energy storage is 3–5 times larger in the deep than in the shallow model and increases progressively with additional soil layers until the model depth reaches about 200 m. While the contents of Part I focus on the sensitivity of subsurface thermodynamics to enlarging the space for energy, Part II addresses the sensitivity to changing the space for water and improving hydrological and phase-change interactions. %0 journal article %@ 1386-0291 %A Braune, S.,Bäckemo, J.,Lau, S.,Heuchel, M.,Kratz, K.,Jung, F.,Reinthaler, M.,Lendlein, A. %D 2021 %J Clinical Hemorheology and Microcirculation %N 4 %P 367-380 %R doi:10.3233/CH-201029 %T The influence of different rewetting procedures on the thrombogenicity of nanoporous poly(ether imide) microparticles %U https://doi.org/10.3233/CH-201029 4 %X Nanoporous microparticles prepared from poly(ether imide) (PEI) are discussed as candidate adsorber materials for the removal of uremic toxins during apheresis. Polymers exhibiting such porosity can induce the formation of micro-gas/air pockets when exposed to fluids. Such air presenting material surfaces are reported to induce platelet activation and thrombus formation. Physical or chemical treatments prior to implantation are discussed to reduce the formation of such gas nuclei. Here, we report about the influence of different rewetting procedures – as chemical treatments with solvents – on the thrombogenicity of hydrophobic PEI microparticles and PEI microparticles hydrophilized by covalent attachment of poly(vinyl pyrrolidone) (PVP) of two different chain lengths. Autoclaved dry PEI particles of all types with a diameter range of 200 – 250 μm and a porosity of about 84% ±2% were either rewetted directly with phosphate buffered saline (24 h) or after immersion in an ethanol-series. Thrombogenicity of the particles was studied in vitro using human sodium citrated whole blood (60 min, 5 rpm vertical rotation). Numbers of non-adherent platelets were quantified, and adhesion of blood cells was qualitatively analyzed by bright field microscopy. Platelet activation (percentage of CD62P positive platelets and amounts of soluble P-Selectin) and platelet function (PFA100 closure times) were analysed. Retention of blood platelets on the particles was similar for all particle types and both rewetting procedures. Non-adherent platelets were less activated after contact with ethanol-treated particles of all types compared to those rewetted with phosphate buffered saline as assessed by a reduced number of CD62P-positive platelets and reduced amounts of secreted P-Selectin (P < 0.05 each). Interestingly, the hydrophilic surfaces significantly increased the number of activated platelets compared to hydrophobic PEI regardless of the rewetting agent. This suggests that, apart from wettability, other material properties might be more important to regulate platelet activation. PFA100 closure times were reduced and within the reference ranges in the ethanol group, however, significantly increased in the saline group. No substantial difference was detected between the tested surface modifications. In summary, rewetting with ethanol resulted in a reduced thrombogenicity of all studied microparticles regardless of their wettability, most likely resulting from the evacuation of air from the nanoporous particles. %0 journal article %@ 1422-0067 %A Lau, S.,Gossen, M.,Lendlein, A.,Jung, F. %D 2021 %J International Journal of Molecular Sciences %N 2 %P 978 %R doi:10.3390/ijms22020978 %T Venous and Arterial Endothelial Cells from Human Umbilical Cords: Potential Cell Sources for Cardiovascular Research %U https://doi.org/10.3390/ijms22020978 2 %X Although cardiovascular devices are mostly implanted in arteries or to replace arteries, in vitro studies on implant endothelialization are commonly performed with human umbilical cord-derived venous endothelial cells (HUVEC). In light of considerable differences, both morphologically and functionally, between arterial and venous endothelial cells, we here compare HUVEC and human umbilical cord-derived arterial endothelial cells (HUAEC) regarding their equivalence as an endothelial cell in vitro model for cardiovascular research. No differences were found in either for the tested parameters. The metabolic activity and lactate dehydrogenase, an indicator for the membrane integrity, slightly decreased over seven days of cultivation upon normalization to the cell number. The amount of secreted nitrite and nitrate, as well as prostacyclin per cell, also decreased slightly over time. Thromboxane B2 was secreted in constant amounts per cell at all time points. The Von Willebrand factor remained mainly intracellularly up to seven days of cultivation. In contrast, collagen and laminin were secreted into the extracellular space with increasing cell density. Based on these results one might argue that both cell types are equally suited for cardiovascular research. However, future studies should investigate further cell functionalities, and whether arterial endothelial cells from implantation-relevant areas, such as coronary arteries in the heart, are superior to umbilical cord-derived endothelial cells. %0 conference paper %@ 1613-0073 %A Joseph, R.,Chauhan, A.,Eschke, C.,Ihsan, A.Z.,Jalali, M.,Jäntsch, U.,Jung, N.,Shyam Kumar, C.N.,Kübel, C.,Lucas, C.,Mail, M.,Mazilkin, A.,Neidiger, C.,Panighel, M.,Sandfeld, S.,Stotzka, R.,Thelen, R.,Aversa, R. %D 2021 %J CEUR Workshop Proceedings : Supplementary 23rd International Conference on Data Analytics and Management in Data Intensive Domains, DAMDID/RCDL 2021 %N %P 265-277 %T Metadata schema to support FAIR data in scanning electron microscopy %U %X The development and the adoption of metadata schemas and standards are a key aspect in data management. In this paper, we introduce our approach to a metadata model in the field of Materials Science. We present the specific use case of a metadata schema for Scanning Electron Microscopy, a characterization technique which is routinely used in Materials Science. This metadata schema is aiming to be a de-facto standard which will be openly available for reuse and further extension to other electron microscopy techniques. Copyright © 2021 for this paper by its authors. %0 journal article %@ 1386-0291 %A Zhou, S.,Di Luca, M.,Xu, X.,Ma, N.,Jung, F.,Lendlein, A. %D 2021 %J Clinical Hemorheology and Microcirculation %N 4 %P 609-623 %R doi:10.3233/CH-211250 %T Defeating antibiotic-resistant bacteria with protein-resistant polyGGE film %U https://doi.org/10.3233/CH-211250 4 %X Biofouling on medical device surfaces, which is initiated by protein adsorption and adhesion of microbes especially the antibiotic-resistant bacteria, attracts global attention for centuries due to its enduring challenges in healthcare. Here, the antifouling effect of hydrophilic poly(glycerol glycidyl ether) (polyGGE) film is explored in comparison to hemocompatible and protein-resistant control polymers. The chemical and thermomechanical stability of polyGGE in hydrated conditions at body temperature was achieved via adjusting UV curing and KOH quenching time. The polyGGE surface is inert to the plasma protein adsorption and interfered the metabolism conditions, biofilm formation and growth of both Gram negative (Gram–) and antibiotic-resistant Gram positive (Gram+) bacteria. These results indicate the potential application of polyGGE for combating the risk of hospital-acquired infections and preventing drug-resistant superbug spreading. %0 journal article %@ 1386-0291 %A Zhou, S.,Xu, X.,Ma, N.,Jung, F.,Lendlein, A. %D 2021 %J Clinical Hemorheology and Microcirculation %N 4 %P 597-608 %R doi:10.3233/CH-211241 %T Influence of sterilization conditions on sulfate-functionalized polyGGE %U https://doi.org/10.3233/CH-211241 4 %X Sulfated biomolecules are known to influence numerous biological processes in all living organisms. Particularly, they contribute to prevent and inhibit the hypercoagulation condition. The failure of polymeric implants and blood contacting devices is often related to hypercoagulation and microbial contamination. Here, bioactive sulfated biomacromolecules are mimicked by sulfation of poly(glycerol glycidyl ether) (polyGGE) films. Autoclaving, gamma-ray irradiation and ethylene oxide (EtO) gas sterilization techniques were applied to functionalized materials. The sulfate group density and hydrophilicity of sulfated polymers were decreased while chain mobility and thermal degradation were enhanced post autoclaving when compared to those after EtO sterilization. These results suggest that a quality control after sterilization is mandatory to ensure the amount and functionality of functionalized groups are retained. %0 journal article %@ 1811-1602 %A Jungclaus, J.,Bothe, O.,Garcia-Bustamante, E.,González-Rouco, J.,Neukom, R.,Schurer, A. %D 2021 %J Past Global Changes Magazine %N 2 %P 72-73 %R doi:10.22498/pages.29.2.72 %T Simulating the Common Era: The Past2K working group of PMIP %U https://doi.org/10.22498/pages.29.2.72 2 %X Simulations of Common Era climate evolution coordinated by PMIP's "Past2K" working group together with multi-proxy reconstructions from the PAGES 2k Network provide pivotal understanding for the evolution of the modern climate system and for expected changes in the near future. %0 journal article %@ 1525-755X %A Steinert, N.,González-Rouco, J.,de Vrese, P.,García-Bustamante, E.,Hagemann, S.,Melo-Aguilar, C.,Jungclaus, J.,Lorenz, S. %D 2021 %J Journal of Hydrometeorology %N 12 %P 3231-3254 %R doi:10.1175/JHM-D-21-0023.1 %T Increasing the Depth of a Land Surface Model. Part II: Temperature Sensitivity to Improved Subsurface Thermodynamics and Associated Permafrost Response %U https://doi.org/10.1175/JHM-D-21-0023.1 12 %X The impact of various modifications of the JSBACH land surface model to represent soil temperature and cold-region hydro-thermodynamic processes in climate projections of the twenty-first century is examined. We explore the sensitivity of JSBACH to changes in the soil thermodynamics, energy balance and storage, and the effect of including freezing and thawing processes. The changes involve 1) the net effect of an improved soil physical representation and 2) the sensitivity of our results to changed soil parameter values and their contribution to the simulation of soil temperatures and soil moisture, both aspects being presented in the frame of an increased bottom boundary depth from 9.83 to 1418.84 m. The implementation of water phase changes and supercooled water in the ground creates a coupling between the soil thermal and hydrological regimes through latent heat exchange. Momentous effects on subsurface temperature of up to ±3 K, together with soil drying in the high northern latitudes, can be found at regional scales when applying improved hydro-thermodynamic soil physics. The sensitivity of the model to different soil parameter datasets is relatively low but shows important implications for the root zone soil moisture content. The evolution of permafrost under preindustrial forcing conditions emerges in simulated trajectories of stable states that differ by 4–6 × 106 km2 and shows large differences in the spatial extent of 105–106 km2 by 2100, depending on the model configuration. %0 journal article %@ 0094-8276 %A Steinert, N.J.,González-Rouco, J.F.,Melo Aguilar, C.A.,García Pereira, F.,García-Bustamante, E.,de Vrese, P.,Alexeev, V.,Jungclaus, J.H.,Lorenz, S.J.,Hagemann, S. %D 2021 %J Geophysical Research Letters %N 20 %P e2021GL094273 %R doi:10.1029/2021GL094273 %T Agreement of Analytical and Simulation-Based Estimates of the Required Land Depth in Climate Models %U https://doi.org/10.1029/2021GL094273 20 %X Previous analytical and simulation-based analyses suggest that deeper land surface models are needed to realistically simulate the terrestrial thermal state in climate models, with implications for land-atmosphere interactions. Analytical approaches mainly focused on the subsurface propagation of harmonics such as the annual temperature signal, and a direct comparison with climate-change model output has been elusive. This study addresses the propagation of a harmonic pulse fitted to represent the timescale and amplitude of anthropogenic warming. Its comparison to land model simulations with stepwise increased bottom boundary depth leads to an agreement between the simulation-based and analytical frameworks for long-term climate trends. Any depth increase gradually decreases the relative error in the subsurface thermodynamics, and a minimum depth of 170 m is recommended to simulate the ground climate adequately. The approach provides an accurate estimate of the required land-model depth for climate-change simulations and assesses the relative bias in insufficiently deep land models. %0 book part %@ %A Xoplaki, E.,Luterbacher, J.,Luther, N.,Behr, L.,Wagner, S.,Jungclaus, J.,Zorita, E.,Toreti, A.,Fleitmann, D.,Izdesbki, A.,Bloomfield, K. %D 2021 %J Climate Change and Ancient Societies in Europe and the Near East %N %P 533-560 %R doi:10.1007/978-3-030-81103-7_18 %T Hydrological Changes in Late Antiquity: Spatio-Temporal Characteristics and Socio-Economic Impacts in the Eastern Mediterranean %U https://doi.org/10.1007/978-3-030-81103-7_18 %X Until now, proxy records have been the primary tool for quantitative reconstructions of the physical world of the ancient and late antique Mediterranean. This chapter demonstrates the combined use of proxy datasets and the hitherto underutilized potential of earth system models in the scientific and historical study of past environmental variations and impacts on human societies. Results from model simulations are able to explain hydroclimatic anomalies observed in the proxy records and provide links to relevant mechanisms. The Late Roman Dry Period and the Late Roman Wet Period of the mid-fourth to early eighth centuries AD are each associated with the increase in the frequency of subsistence crises and with the accelerated infrastructural adaptations of communities and agricultural expansion, respectively. The chapter concludes with an examination of the historical and climatic contexts behind one such anomaly, a subsistence crisis in Cappadocia in the late 300s AD. %0 journal article %@ 1422-0067 %A Schulz, C.,Krüger-Genge, A.,Lendlein, A.,Küpper, J.,Jung, F. %D 2021 %J International Journal of Molecular Sciences %N 3 %P 1493 %R doi:10.3390/ijms22031493 %T Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture %U https://doi.org/10.3390/ijms22031493 3 %X The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used. %0 journal article %@ 1386-0291 %A Krüger-Genge, A.,Tondera, C.,Hauser, S.,Braune, S.,Görs, J.,Roch, T.,Klopfleisch, R.,Neffe, A.,Lendlein, A.,Pietzsch, J.,Jung, F. %D 2021 %J Clinical Hemorheology and Microcirculation %N 3 %P 335-350 %R doi:10.3233/CH-201028 %T Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels %U https://doi.org/10.3233/CH-201028 3 %X Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the “Hen’s egg test on chorioallantoic membrane” (HET-CAM) test and a mouse model. The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants. %0 journal article %@ 2373-9878 %A Krüger-Genge, A.,Hauser, S.,Neffe, A.,Liu, Y.,Lendlein, A.,Pietzsch, J.,Jung, F. %D 2021 %J ACS Biomaterials Science & Engineering %N 2 %P 527-540 %R doi:10.1021/acsbiomaterials.0c01432 %T Response of Endothelial Cells to Gelatin-Based Hydrogels %U https://doi.org/10.1021/acsbiomaterials.0c01432 2 %X The establishment of confluent endothelial cell (EC) monolayers on implanted materials has been identified as a concept to avoid thrombus formation but is a continuous challenge in cardiovascular device engineering. Here, material properties of gelatin-based hydrogels obtained by reacting gelatin with varying amounts of lysine diisocyanate ethyl ester were correlated with the functional state of hydrogel contacting venous EC (HUVEC) and HUVEC’s ability to form a monolayer on these hydrogels. The density of adherent HUVEC on the softest hydrogel at 37 °C (G’ = 1.02 kPa, E = 1.1 ± 0.3 kPa) was significantly lower (125 mm–1) than on the stiffer hydrogels (920 mm–1; G’ = 2.515 and 5.02 kPa, E = 4.8 ± 0.8 and 10.3 ± 1.2 kPa). This was accompanied by increased matrix metalloprotease activity (9 pmol·min–2 compared to 0.6 pmol·min–2) and stress fiber formation, while cell-to-cell contacts were comparable. Likewise, release of eicosanoids (e.g., prostacyclin release of 1.7 vs 0.2 pg·mL–1·cell–1) and the pro-inflammatory cytokine MCP-1 (8 vs <1.5 pg·mL–1·cell–1) was higher on the softer than on the stiffer hydrogels. The expressions of pro-inflammatory markers COX-2, COX-1, and RAGE were slightly increased on all hydrogels on day 2 (up to 200% of the control), indicating a weak inflammation; however, the levels dropped to below the control from day 6. The study revealed that hydrogels with higher moduli approached the status of a functionally confluent HUVEC monolayer. The results indicate the promising potential especially of the discussed gelatin-based hydrogels with higher G’ as biomaterials for implants foreseen for the venous system. %0 journal article %@ 1386-0291 %A Lee, S.,Ganesan, R.,Krüger-Genge, A.,Kratz, K.,Franke, R.,Lendlein, A.,Jung, F. %D 2020 %J Clinical Hemorheology and Microcirculation %N 1 %P 85-98 %R doi:10.3233/CH-190736 %T Substrate-enzyme affinity-based surface modification strategy for endothelial cell-specific binding under shear stress %U https://doi.org/10.3233/CH-190736 1 %X Establishing an endothelial cell (EC) monolayer on top of the blood contacting surface of grafts is considered to be a promising approach for creating a hemocompatible surface. Here we utilized the high affinity interactions between the EC plasma membrane expressed enzyme called endothelin converting enzyme-1 (ECE-1) and its corresponding substrate big Endothelin-1 (bigET-1) to engineer an EC-specific binding surface. Since enzymatic cleavage of substrates require physical interaction between the enzyme and its corresponding substrate, it was hypothesized that a surface with chemically immobilized synthetic bigET-1 will preferentially attract ECs over other types of cells found in vascular system such as vascular smooth muscle cells (VSMCs). First, the expression of ECE-1 was significantly higher in ECs, and ECs processed synthetic bigET-1 to produce ET-1 in a cell number-dependent manner. Such interaction between ECs and synthetic bigET-1 was also detectible in blood. Next, vinyl-terminated self-assembled monolayers (SAMs) were established, oxidized and activated on a glass substrate as a model to immobilize synthetic bigET-1 via amide bonds. The ECs cultured on the synthetic bigET-1-immobilized surface processed larger amount of synthetic bigET-1 to produce ET-1 compared to VSMCs (102.9±5.13 vs. 9.75±0.74 pg/ml). The number of ECs bound to the synthetic bigET-1-immobilized surface during 1 h of shearing (5dyne/cm2) was approximately 3-fold higher than that of VSMCs (46.25±12.61 vs. 15.25±3.69 cells/100×HPF). EC-specific binding of synthetic bigET-1-immobilized surface over a surface modified with collagen, a common substance for cell adhesion, was also observed. The present study demonstrated that using the substrate-enzyme affinity (SEA) of cell type-specific enzyme and its corresponding substrate can be an effective method to engineer a surface preferentially binds specific type of cells. This novel strategy might open a new route toward rapid endothelialization under dynamic conditions supporting the long-term patency of cardiovascular implants. %0 journal article %@ 1386-0291 %A Schulz, C.,Krüger-Genge, A.,Jung, F.,Lendlein, A. %D 2020 %J Clinical Hemorheology and Microcirculation %N 2 %P 201-217 %R doi:10.3233/CH-190775 %T Aptamer supported in vitro endothelialization of poly(ether imide) films %U https://doi.org/10.3233/CH-190775 2 %X Implantation of synthetic small-diameter vascular bypass grafts is often associated with an increased risk of failure, due to thrombotic events or late intimal hyperplasia. As one of the causes an insufficient hemocompatibility of the artificial surface is discussed. Endothelialization of synthetic grafts is reported to be a promising strategy for creating a self-renewing and regulative anti-thrombotic graft surface. However, the establishment of a shear resistant cell monolayer is still challenging. In our study, cyto- and immuno-compatible poly(ether imide) (PEI) films were explored as potential biomaterial for cardiovascular applications. Recently, we reported that the initial adherence of primary human umbilical vein endothelial cells (HUVEC) was delayed on PEI-films and about 9 days were needed to establish a confluent and almost shear resistant HUVEC monolayer. To accelerate the initial adherence of HUVEC, the PEI-film surface was functionalized with an aptamer-cRGD peptide based endothelialization supporting system. With this functionalization the initial adherence as well as the shear resistance of HUVEC on PEI-films was considerable improved compared to the unmodified polymer surface. The in vitro results confirm the general applicability of aptamers for an efficient functionalization of substrate surfaces. %0 journal article %@ 1386-0291 %A Haase, T.,Klopfleisch, R.,Krost, A.,Sauter, T.,Kratz, K.,Peter, J.,Jung, F.,Lendlein, A.,Zohlnhöfer, D.,Rüder, C. %D 2020 %J Clinical Hemorheology and Microcirculation %N 2 %P 163-176 %R doi:10.3233/CH-190748 %T In vivo biocompatibility study of degradable homo- versus multiblock copolymers and their (micro)structure compared to an established biomaterial %U https://doi.org/10.3233/CH-190748 2 %X Copolyetheresterurethane (PDC) is a biodegradable, shape-memory biomaterial, which has been shown to be of low toxicity and pro-angiogenic in vitro. In the present study we examined the in vivo compatibility of PDC as a compression molded film and as electrospun scaffolds and its well established constituent, the homopolymer poly(p-dioxanone) (PPDO), which were compared with the clinically used poly[(vinylidene fluoride)-co-hexafluoropropene] (PVDF) as reference material. The materials were implanted in the subcutaneous tissue of mice and the host responses were analyzed histologically 7 and 28 days after implantation. All materials induced a foreign body response (FRB) including the induction of foreign body giant cells and a peripheral fibrous capsule. PDC, PPDO and PVDF films showed no signs of degradation after 28 days. PDC films showed a significantly reduced associated macrophage layer and fibrous capsule on their surface. Few fragments of PDC and PPDO scaffolds were present at the implantation site, while PVDF scaffolds were still present in large amounts at day 28. Especially aligned electrospun PDC scaffold induced a significantly thinner fibrous and a slightly reduced inflammatory response after 28 days of implantation. In addition, only PDC aligned fibrous scaffold structures induced a significant increase in angiogenesis. In summary, PDC films outperformed PPDO and PVDF films in terms of compatibility, especially in capsule and macrophage layer thickness. Through microstructuring of PDC and PPDO into scaffolds an almost complete degradation was observed after 28 days, while their respective films remained almost unchanged. However, the capsule thickness of all scaffolds was comparable to the films after 28 days. Finally, the parallel arrangement of PDC fibers enabled a strong enhancement of angiogenesis within the scaffold. Hence, material chemistries influence overall compatibility in vivo, while angiogenesis could be influenced more strongly by microstructural parameters than chemical ones. %0 journal article %@ 2059-8521 %A Wischke, C.,Kersting, M.,Welle, A.,Lysyakova, L.,Braune, S.,Kratz, K.,Jung, F.,Franzreb, M.,Lendlein, A. %D 2020 %J MRS Advances %N 14 - 15 %P 773-783 %R doi:10.1557/adv.2020.218 %T Thin hydrogel coatings formation catalyzed by immobilized enzyme horseradish peroxidase %U https://doi.org/10.1557/adv.2020.218 14 - 15 %X Enzymes can be a renewable source of catalytic agents and thus be interesting for sustainable approaches to create and modify functional materials. Here, thin hydrogel layers were prepared as thin coatings on hard substrates by immobilized horseradish peroxidase. Hydrophilic 4-arm star shaped telechelics from oligo(ethylene glycol) bearing on average 55% end groups derived from aromatic amino acids served as monomers and enzymatic substrates. Shifts of the contact angle from 84° to 62° for the wetting process and of zeta potential towards the neutral range illustrated an alteration of physicochemical properties of the model surfaces by a hydrophilic shielding. Time-of-flight secondary ion mass spectrometry (ToF-SIMS), quartz crystal microbalance and atomic force microscopy (AFM) experiments enabled the qualitative and quantitative proof of hydrogel deposition at the interface with thicknesses in the medium nanometer size range. Conceptually, as the immobilized enzyme becomes entrapped in the hydrogel and the crosslinking mechanism bases on a radical reaction after enzymatic activation of the monomers with a limited diffusivity and lifetime, the formed network material can be assumed to be inhomogeneous on the molecular level. On the macroscale, however, relative homogeneity of the coating was observed via ToF-SIMS and AFM mapping. As an exemplary functional evaluation in view of bioanalytical applications, the thrombogenicity of the coating was studied in static tests with human blood from several donors. In the future, this “coating-from” approach may be explored for cell culture substrate coatings, for protein/biofilm repellence in technical applications, or in bioanalytical devices. %0 journal article %@ 0887-2333 %A Lau, S.,Rangarajan, R.,Philidet, C.,Krüger-Genge, A.,Braune, S.,Kammerer, S.,Küpper, J.,Lendlein, A.,Jung, F. %D 2020 %J Toxicology in Vitro %N %P 104685 %R doi:10.1016/j.tiv.2019.104685 %T Effects of acrolein in comparison to its prodrug cyclophosphamide on human primary endothelial cells in vitro %U https://doi.org/10.1016/j.tiv.2019.104685 %X Cyclophosphamide (CPA) is one of the most successful anticancer prodrugs that becomes effective after biotransformation in the liver resulting in the toxic metabolite acrolein. Cancer is often accompanied by thromboembolic events, which might be a result of dysfunctional endothelial cells due to CPA treatment.,Here, the effect of 1 mM CPA or acrolein (10/50/100/500 μM) on human umbilical vein endothelial cells (HUVECs) was analyzed after two days of treatment.,The addition of CPA or 10 μM acrolein did not affect HUVECs. However, concentrations of 100 μM and 500 μM acrolein significantly reduced the number of adherent cells by 86 ± 13% and 99 ± 1% and cell viability by 51 ± 29% and 93 ± 8% compared to the control. Moreover, pronounced stress fibers as well as multiple nuclei were observed and von Willebrand factor (vWF) was completely released. Lactate dehydrogenase was 8.5 ± 7.0-fold and 252.9 ± 42.9-fold increased showing a loss of cell membrane integrity. The prostacyclin and thromboxane secretion was significantly increased by the addition of 500 μM acrolein (43.1 ± 17.6-fold and 246.4 ± 106.3-fold) indicating cell activation/pertubation.,High doses of acrolein led to HUVEC death and loss of vWF production. This effect might be associated with the increased incidence of thromboembolic events in cancer patients treated with high doses of CPA. %0 journal article %@ 1386-0291 %A Lau, S.,Rangarajan, R.,Krüger-Genge, A.,Braune, S.,Küpper, J.,Lendlein, A.,Jung, F. %D 2020 %J Clinical Hemorheology and Microcirculation %N 1 %P 93-107 %R doi:10.3233/CH-199238 %T Age-related morphology and function of human arterial endothelial cells %U https://doi.org/10.3233/CH-199238 1 %X Endothelialization of cardiovascular implants is regarded as a promising strategy for long-term compatibility. While umbilical vein endothelial cells are typically applied in research, human arterial endothelial cells (HAEC) from elderly donors would be the obvious source for autologous cellularization strategies.,In our approach, HAEC from 16 donors of varying age (16–63 years) were divided into two groups (<30 years and >30 years) and analyzed regarding morphology, viability, proliferation, function and senescence status.,No age-related differences were found regarding morphology, viability, density, prostacyclin and nitrite secretion or collagen and laminin production. However, the metabolic activity was slightly decreased (p = 0.0374) and the membrane integrity marginally impaired (p = 0.0404) in cells from older donors. Two out of three senescence assays detected more senescence markers in cells from older donors.,According to the assays applied here, HAEC from young and elderly donors up to the age of 63 years could be judged equally suitable for autologous cellularization strategies. However, this finding should be regarded with caution due to the extremely large variability between individual donors. Further studies comprising a larger sample size are necessary to investigate this issue more thoroughly. %0 journal article %@ 1748-9326 %A Ljungqvist, F.,Seim, A.,Krusic, P.,Gonzalez-Rouco, F.,Werner, J.,Cook, E.,Zorita, E.,Luterbacher, J.,Xoplaki, E.,Destouni, G.,Garcia-Bustamante, E.,Melo-Aguilar, C.,Seftigen, K.,Wang, J.,Gagen, M.,Esper, J.,Solomina, O.,Fleitmann, D.,Büntgen, U. %D 2019 %J Environmental Research Letters %N %P 084015 %R doi:10.1088/1748-9326/ab2c7e %T European warm-season temperature and hydroclimate since 850 CE %U https://doi.org/10.1088/1748-9326/ab2c7e %X The long-term relationship between temperature and hydroclimate has remained uncertain due to the short length of instrumental measurements and inconsistent results from climate model simulations. This lack of understanding is particularly critical with regard to projected drought and flood risks. Here we assess warm-season co-variability patterns between temperature and hydroclimate over Europe back to 850 CE using instrumental measurements, tree-ring based reconstructions, and climate model simulations. We find that the temperature–hydroclimate relationship in both the instrumental and reconstructed data turns more positive at lower frequencies, but less so in model simulations, with a dipole emerging between positive (warm and wet) and negative (warm and dry) associations in northern and southern Europe, respectively. Compared to instrumental data, models reveal a more negative co-variability across all timescales, while reconstructions exhibit a more positive co-variability. Despite the observed differences in the temperature–hydroclimate co-variability patterns in instrumental, reconstructed and model simulated data, we find that all data types share relatively similar phase-relationships between temperature and hydroclimate, indicating the common influence of external forcing. The co-variability between temperature and soil moisture in the model simulations is overestimated, implying a possible overestimation of temperature-driven future drought risks. %0 journal article %@ 1422-0067 %A Jung, O.,Porchetta, D.,Schroeder, M.-L.,Klein, M.,Wegner, N.,Walther, F.,Feyerabend, F.,Barbeck, M.,Kopp, A. %D 2019 %J International Journal of Molecular Sciences %N 19 %P 4859 %R doi:10.3390/ijms20194859 %T In vivo simulation of magnesium degradability using a new fluid dynamic bench testing approach %U https://doi.org/10.3390/ijms20194859 19 %X The degradation rate of magnesium (Mg) alloys is a key parameter to develop Mg-based biomaterials and ensure in vivo-mechanical stability as well as to minimize hydrogen gas production, which otherwise can lead to adverse effects in clinical applications. However, in vitro and in vivo results of the same material often differ largely. In the present study, a dynamic test bench with several single bioreactor cells was constructed to measure the volume of hydrogen gas which evolves during magnesium degradation to indicate the degradation rate in vivo. Degradation medium comparable with human blood plasma was used to simulate body fluids. The media was pumped through the different bioreactor cells under a constant flow rate and 37 °C to simulate physiological conditions. A total of three different Mg groups were successively tested: Mg WE43, and two different WE43 plasma electrolytically oxidized (PEO) variants. The results were compared with other methods to detect magnesium degradation (pH, potentiodynamic polarization (PDP), cytocompatibility, SEM (scanning electron microscopy)). The non-ceramized specimens showed the highest degradation rates and vast standard deviations. In contrast, the two PEO samples demonstrated reduced degradation rates with diminished standard deviation. The pH values showed above-average constant levels between 7.4–7.7, likely due to the constant exchange of the fluids. SEM revealed severe cracks on the surface of WE43 after degradation, whereas the ceramized surfaces showed significantly decreased signs of corrosion. PDP results confirmed the improved corrosion resistance of both PEO samples. While WE43 showed slight toxicity in vitro, satisfactory cytocompatibility was achieved for the PEO test samples. In summary, the dynamic test bench constructed in this study enables reliable and simple measurement of Mg degradation to simulate the in vivo environment. Furthermore, PEO treatment of magnesium is a promising method to adjust magnesium degradation. %0 conference lecture %@ %A Braune, S.,Xourida, M.,Maier, A.,Reinthaler, M.,Kratz, K.,Latour, R.,Lendlein, A.,Jung, F. %D 2019 %J 38. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie %N %P %T Translocation and release of Von Willebrand factor in the adherent platelet %U %X The adsorption of proteins from blood plasma, molecules secreted by blood cells - such as the activated platelet - participates in orchestrating the overall hemocompatibility of cardiovascular implants. Here, we studied the translocation and secretion of von Willebrand factor (VWF) from human platelets on implant materials using three-dimensional super resolution microscopy in order to explore how local secretion processes can influence thrombotic processes. We hypothesize that beyond the secretion of VWF from the platelet granula, also not secreted VWF might be available on blood contacting implant surfaces after the full activation of the adherent platelet. %0 conference lecture %@ %A Lau, S.,Rangarajan, R.,Krüger-Genge, A.,Braune, S.,Küpper, J.,Lendlein, A.,Jung, F. %D 2019 %J 38. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie %N %P %T Age-related morphology and function of human arterial endothelial cells %U %X The world health organization defines ageing as a natural, inevitable and multifactorial process that occurs at genetic, molecular, cellular, organ and system levels. Among the biological structures that are affected by ageing, endothelial cells are of utmost importance due to their role in regulating blood flow and vascular hemostasis. In vitro cultivation of endothelial cells over several passages leads to morphological and functional changes which has been described as replicative senescence. However, it is unclear whether these changes in vitro reflect human cellular ageing in vivo. A recent study analyzed freshly isolated endothelial cells, which were removed from vessels via J-wires, and showed that the expression of senescence markers p53, p16 and p21 was increased in endothelial cells from aged donors [1]. Moreover, it was observed that tumors in the later stage of life (>80 years) grow slower suggesting that cell growth is decelerated with increasing age. However, clear evidence for this is missing. %0 journal article %@ 2192-2659 %A Braune, S.,Latour, R.,Reinthaler, M.,Landmesser, U.,Lendlein, A.,Jung, F. %D 2019 %J Advanced Healthcare Materials %N 21 %P 1900527 %R doi:10.1002/adhm.201900527 %T In Vitro Thrombogenicity Testing of Biomaterials %U https://doi.org/10.1002/adhm.201900527 21 %X The short‐ and long‐term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge‐based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed. %0 journal article %@ 1386-0291 %A Lamby, P.,Krueger-Genge, A.,Franke, F.P.,Mrowietz, C.,Falter, J.,Graf, S.,Schellenberg, E.L.,Jung, F.,Prantl, L. %D 2019 %J Clinical Hemorheology and Microcirculation %N 1 %P 261-270 %R doi:10.3233/CH-199009 %T Effect of iodinated contrast media on the oxygen tension in the renal cortico-medullary region of pigs %U https://doi.org/10.3233/CH-199009 1 %X Repeated injections of iodinated contrast media (CM) can lead to a deterioration of the renal blood flow, can redistribute blood from the renal cortex to other parts of the kidney and can cause small decreases of the blood flow in cortical capillaries, a significant reduction in blood flow in peritubular capillaries and a significant reduction in blood flow in the vasa recta. Therefore, a study in pigs was designed, to show whether the repeated injection of CM boli, alone, can cause a reduction of oxygenation in the cortico-medullar renal tissue – the region with the highest oxygen demand in the kidney - of pigs.,While the mean pO2-value had only decreased by 0.3 mmHg from 29.9±4.3 mmHg to 29.6±4.3 mmHg (p = 0.8799) after the tenth Iodixanol bolus, it decreased by 5.9 mmHg from 34.0±4.3 mmHg to 28.1±4.3 mmHg after the tenth Iopromide bolus (p = 0.044). This revealed a remarkable difference in the influence of these CM on the oxygen partial pressure in the kidney.,Repeated applications of CM had a significant influence on the renal oxygen partial pressure. In line with earlier studies showing a redistribution of blood from the cortex to other renal areas, this study revealed that Iodixanol – in contrast to Iopromide - induced no changes in the pO2 in the cortico-medullar region which confirms that Iodixanol did not hinder the flow of blood through the renal micro-vessels. These results are in favor of a hypothesis from Brezis that a microcirculatory disorder might be the basis for the development of CI-AKI. %0 journal article %@ 1386-0291 %A Kuhnla, A.,Reinthaler, M.,Braune, S.,Maier, A.,Pindur, G.,Lendlein, A.,Jung, F. %D 2019 %J Clinical Hemorheology and Microcirculation %N 4 %P 425-435 %R doi:10.3233/CH-199006 %T Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age %U https://doi.org/10.3233/CH-199006 4 %X Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80–98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3% ±3.3% to 10.9% ±5.9%). The maximum induced aggregation decreased with age for ristocetin (from 85.8% ±7.2% to 75.0% ±7.8%), ADP (from 88.5% ±4.6% to 64.8% ±7.3%) and collagen (from 89.5% ±3.0% to 64.0% ±4.0%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed “platelet exhaustion”. In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans. %0 journal article %@ 1386-0291 %A Reinthaler, M.,Baeckemo-Johansson, J.,Braune, S.,Al-Hindwan, H.S.A.,Lendlein, A.,Jung, F. %D 2019 %J Clinical Hemorheology and Microcirculation %N 2 %P 183-191 %R doi:10.3233/CH-189410 %T Shear-induced platelet adherence and activation in an in-vitro dynamic multiwell-plate system %U https://doi.org/10.3233/CH-189410 2 %X Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials.,Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne · cm–2) and high (arterial shear stress: 22.2 dyne · cm–2) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined.,Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend.,Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions. %0 journal article %@ 1386-0291 %A Shin, E.-S.,Chung, J.-H.,Park, S.G.,Saleh, A.,Lam, Y.-Y.,Bhak, J.,Jung, F.,Morita, S.,Brachmann, J. %D 2019 %J Clinical Hemorheology and Microcirculation %N 2 %P 283-291 %R doi:10.3233/CH-180485 %T Comparison of exercise electrocardiography and magnetocardiography for detection of coronary artery disease using ST-segment fluctuation score %U https://doi.org/10.3233/CH-180485 2 %X BACKGROUND:,Exercise electrocardiography (ECG) is frequently used as a diagnostic measure in patients with suspected coronary artery disease (CAD). However, it has low sensitivity for the detection of CAD. Magnetocardiography (MCG) has been proposed as an alternative tool to accurately diagnose CAD.,OBJECTIVE:,To date, a direct comparison of MCG to ECG has not been performed. This study sought to compare them for predicting the presence of significantly obstructive CAD.,METHODS:,The patients with chest pain or other symptoms suggestive of CAD were enrolled in the analysis. All the patients underwent a clinical evaluation, exercise ECG, a MCG exercise test, and coronary angiography (CA). CAD was defined as stenosis ≥70% stenosis in at least one major coronary artery on quantitative analysis of CA.,RESULTS:,We prospectively enrolled 202 consecutive patients who suggested CAD. The prevalence of CAD on CA was 39.1%. Sensitivity and accuracy for CAD diagnosis was higher for MCG compared with exercise ECG (sensitivities 68.4% and 40.5%, p <0.001, specificities 95.1% and 91.1%, p = 0.267, and accuracies 84.7% and 71.3%, p <0.001, respectively). There was no incremental diagnostic value of combined MCG and ECG to detect coronary artery disease (p = 0.357).,CONCLUSIONS:,For the patients with intermediate to high risk of CAD, MCG exercise test provides better diagnostic accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG. %0 journal article %@ 1726-4170 %A Charrieau, L.,Ljung, K.,Schenk, F.,Daewel, U.,Kritzberg, E.,Filipsson, H. %D 2019 %J Biogeosciences %N 19 %P 3835-3852 %R doi:10.5194/bg-16-3835-2019 %T Rapid environmental responses to climate-induced hydrographic changes in the Baltic Sea entrance %U https://doi.org/10.5194/bg-16-3835-2019 19 %X The Öresund (the Sound), which is a part of the Danish straits, is linking the marine North Sea and the brackish Baltic Sea. It is a transition zone where ecosystems are subjected to large gradients in terms of salinity, temperature, carbonate chemistry, and dissolved oxygen concentration. In addition to the highly variable environmental conditions, the area is responding to anthropogenic disturbances in, e.g., nutrient loading, temperature, and pH. We have reconstructed environmental changes in the Öresund during the last ca. 200 years, and especially dissolved oxygen concentration, salinity, organic matter content, and pollution levels, using benthic foraminifera and sediment geochemistry. Five zones with characteristic foraminiferal assemblages were identified, each reflecting the environmental conditions for the respective period. The largest changes occurred around 1950, when the foraminiferal assemblage shifted from a low diversity fauna dominated by the species Stainforthia fusiformis to higher diversity and abundance and dominance of the Elphidium species. Concurrently, the grain-size distribution shifted from clayey to sandier sediment. To explore the causes of the environmental changes, we used time series of reconstructed wind conditions coupled with large-scale climate variations as recorded by the North Atlantic Oscillation (NAO) index as well as the ECOSMO II model of currents in the Öresund area. The results indicate increased changes in the water circulation towards stronger currents in the area after the 1950s. The foraminiferal fauna responded quickly (<10 years) to the environmental changes. Notably, when the wind conditions, and thereby the current system, returned in the 1980s to the previous pattern, the foraminiferal assemblage did not rebound. Instead, the foraminiferal faunas displayed a new equilibrium state. %0 journal article %@ 1386-0291 %A Mrowietz, C.,Franke, R.P.,Pindur, G.,Sternitzky, R.,Jung, F.,Wolf, U. %D 2019 %J Clinical Hemorheology and Microcirculation %N 2 %P 129-135 %R doi:10.3233/CH-189402 %T Evaluation of Laser-Doppler-Fluxmetry for the diagnosis of microcirculatory disorders %U https://doi.org/10.3233/CH-189402 2 %X BACKGROUND:,The laser Doppler fluxmetry (LDF) is a non-invasive method to assess skin blood perfusion, measuring the flow of blood cells inside a tissue volume without harming the tissue. In the diagnosis of skin circulation disorders, the results of the LDF measurement are generally used in such a way that “normal” (or non-ill) or “pathological” values are achieved by comparison with a reference sample, for example of apparently healthy subjects.,MATERIAL AND METHODS:,In this study, the values of LDF for the diagnosis of microcirculatory disorders in patients with coronary artery disease (n = 20) or in patients with microcirculatory disorders, already diagnosed by capillary microscopy (n = 46), were examined.,RESULTS:,The mean values of LD amplitudes in the four frequency windows for patients with coronary artery disease were in the reference range. However, some of the patients showed reduced LD values: in eleven of the twenty patients, one or more mean LD amplitudes were below the reference range. Four of the eleven patients had pathologically decreased capillary erythrocyte velocities of v ery = 0.09–0.21 [mm/s], while the other seven patients had normal blood circulation at rest.,For all patients with a proven cutaneous microcirculatory disorder, the mean LD amplitude in at least one of the frequency windows FF2 to FF4 was pathologically reduced.,CONCLUSION:,The Laser-Doppler fluxmetry method used in the study allows the reliable diagnosis of cutaneous microcirculatory disorders. %0 conference lecture %@ %A Braune, S.,Xourida, M.,Maier, A.,Reinthaler, M.,Kratz, K.,Latour, R.,Lendlein, A.,Jung, F. %D 2019 %J 38. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheoligie (DGKMH) %N %P %T Translocation and release of von Willebrand factor in the adherent and activated platelet %U %X %0 journal article %@ 0300-483X %A Steinbrecht, S.,Koenig, R.,Schmidtke, K.-U.,Herzog, N.,Scheibner, K.,Krueger-Genge, A.,Jung, F.,Kammerer, S.,Kuepper, J.-H. %D 2019 %J Toxicology %N %P 37-47 %R doi:10.1016/j.tox.2018.11.008 %T Metabolic activity testing can underestimate acute drug cytotoxicity as revealed by HepG2 cell clones overexpressing cytochrome P450 2C19 and 3A4 %U https://doi.org/10.1016/j.tox.2018.11.008 %X Preclinical drug safety assessment includes in vitro studies with physiologically relevant cell cultures. As an in vitro system for hepatic toxicology testing, we have been generating cell clones of human hepatoblastoma cell line HepG2 by lentiviral transduction of phase I cytochrome P450 (CYP) enzymes. Here, we present a stable CYP2C19-overexpressing HepG2 cell clone (HepG2-2C19 C1) showing an enzyme activity of approximately 82 pmol x min−1 x mg−1 total cellular protein. The phenotypic stability over several passages of HepG2-2C19 C1 renders them to be a suitable reference cell clone for benchmarking CYP2C19 enzyme activity. In addition, we were interested to analyze acute cytotoxicity of the model drug cyclophosphamide (CPA) metabolized by HepG2-2C19 C1 and by a previously generated CYP3A4-overexpressing HepG2 cell clone. Upon 10 mM CPA exposure, we were able to detect its metabolites 4-hydroxy-cyclophosphamide and acrolein in CYP3A4- and CYP2C19-expressing cell clones, but not in parental HepG2 cell line. XTT and ATP assays showed a modest reduction of cell viability of not more than 50% with high dose (10 mM) CPA treatment. By contrast, dramatic acute cytotoxic effects of CPA were evident by the formation of nuclear γH2AX foci and by increased cell death events. These effects were paralleled by substantial decreases of cell membrane integrity as measured by the trypan blue exclusion test. Our data on CYP enzyme overexpressing HepG2 cell clones clearly show that cytotoxicity of CPA is dramatically underestimated by standard metabolic activity tests. Thus, additional tests to quantitate DNA damage formation and cell death induction might be required to realistically assess cytotoxicity of such compounds. %0 journal article %@ 1386-0291 %A da Silva, N.P.B.,Jung, E.M.,Jung, F.,Schlitt, H.J.,Hornung, M. %D 2019 %J Clinical Hemorheology and Microcirculation %N 4 %P 423-431 %R doi:10.3233/CH-189307 %T VueBox® perfusion analysis of Contrast-Enhanced Ultrasound (CEUS) examinations in patients with primary hyperparathyroidism for preoperative detection of parathyroid gland adenoma %U https://doi.org/10.3233/CH-189307 4 %X AIM:,Aim of this study was to firstly describe reproducible, objective perfusion parameters of contrast-enhanced ultrasound (CEUS) kinetics of parathyroid gland adenoma (PA) using perfusion analysis software (VueBox®, Bracco, Italy). Thereby the efficiency of quantitative CEUS for characterization of PA should be evaluated comparing US to postoperative histopathological findings after PA resection.,MATERIAL AND METHODS:,42 patients with symptoms/lab work suggestive of pHPT presented a parathyroid gland lesion in B-mode US, which was consequently analyzed by dynamic CEUS. CEUS was performed by one experienced examiner after i.v.-injection of max. 2.4 ml sulphurhexaflouride microbubbles saving digital DICOM cine loops (up to 25 s) and images. PA were evaluated during arterial, venous and late phase (up to 3 min.) for perfusion characterization. A retrospective, blinded VueBox® perfusion analysis of arterial phase of 28/42 PA was performed by a second, independent examiner placing 3 ROIs manually in the PA (center, rim of PA, surrounding thyroid gland tissue) to objectify findings. US findings were correlated to postoperative histology after PA resection.,RESULTS:,Out of 42 patients with PA findings in CEUS, perfusion analysis could be performed in 28/42 cases only as some CEUS cine loops had too much moving. In three cases the second examiner could not detect PA retrospectively, in 25 cases PA were characterized correctly resulting in a sensitivity rate of 89.3 %. VueBox® perfusion analysis confirmed that PA present a persisting hypervascularization of the rim with higher TTP (mean 7.93 s centrally, 8.36 s rim-sided), mTT (mean 56.6 s centrally, 64.5 s rim-sided) and lower PE (mean 10542.93 rm2 centrally, 8909.21 rm2 rim-sided) peripherally followed by a central wash-out during later phases. RT was comparable in all defined regions.,CONCLUSION:,VueBox® analysis of parathyroid gland CEUS examinations seemed to be a valuable tool for quantification of a PA’s perfusion and can help to detect and localize hyperfunctional parathyroid glands prior to surgery. %0 journal article %@ 1386-0291 %A Shin, E.-S.,Park, S.G.,Saleh, A.,Lam, Y.-Y.,Bhak, J.,Jung, F.,Morita, S.,Brachmann, J. %D 2019 %J Clinical Hemorheology and Microcirculation %N 4 %P 365-373 %R doi:10.3233/CH-189301 %T Magnetocardiography scoring system to predict the presence of obstructive coronary artery disease %U https://doi.org/10.3233/CH-189301 4 %X BACKGROUND:,Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia.,OBJECTIVE:,This study sought to develop a novel scoring system of MCG for predicting the presence of significant obstructive coronary artery disease (CAD).,METHODS:,In a training set of 108 subjects, predictors of ≥70% stenosis in at least one major coronary vessel were prospectively identified from MCG variables. The final model was then retrospectively validated in a separate set of 45 subjects.,RESULTS:,In the multivariable logistic regression, among those in the training set, elevated scores were predictive of ≥70% stenosis in all subjects (OR: 40.85; 95% CI: 6.28–265.90; p < 0.001). In the validation set, the score had an area under the receiver-operating characteristic curve of 0.91 (p < 0.001) for ≥70% stenosis. At an optimal cutoff, the score had 89% sensitivity, 77% specificity, 74% positive predictive value (PPV), 91% negative predictive value (NPV), and 82% accuracy for ≥70% stenosis. Partitioning the score into three levels of predicted risk, 91% of subjects could be identified or excluding CAD (81% PPV and 84% NPV).,CONCLUSION:,We described an MCG score with high accuracy for predicting the presence of anatomically significant CAD. %0 journal article %@ 1386-0291 %A Krüger-Genge, A.,Fuhrmann, R.,Franke, R.-P.,Jung, F. %D 2019 %J Clinical Hemorheology and Microcirculation %N 2 %P 175-181 %R doi:10.3233/CH-189409 %T Effect of lipopolysaccharide on the adherence of human umbilical vein endothelial cells (HUVEC) on a natural substrate %U https://doi.org/10.3233/CH-189409 2 %X Polymers are often contaminated with lipopolysaccharides also known as endotoxins. Even small amounts of endotoxins can have strong effects on endothelial cell function so that the endothelialisation of cardiovascular implants might be hampered. An open question is how endothelial cells seeded on a body foreign substrate respond to shear load after adding Lipid A (LPA), the domain, which is responsible for much of the toxicity of gram-negative bacteria, and whether morphological changes of endothelial cells occur.,LPA supplementation to the culture medium in increasing concentrations (5, 25 and 50μg/ml) resulted in progressive reductions of the density of adherent HUVEC after shear load (p < 0.001). 48% of the HUVEC in control cultures (0μg/ml LPA) were still adherent after 2 hours of shearing at 6 dyne/cm2, while 80 minutes after addition of 50μg/ml LPA, 88% of the HUVEC had already detached from the substrate and after 100 minutes no more HUVEC were attached.,The results demonstrate that endotoxins are of extreme importance for the behavior of HUVEC and that in vivo pathologies can be increasingly simulated in vitro. %0 journal article %@ 1991-959X %A Hordoir, R.,Axell, L.,Hoeglung, A.,Dieterich, C.,Fransner, F.,Groeger, M.,Liu, Y.,Pemberton, P.,Schimanke, S.,Andersson, H.,Ljungemyr, P.,Nygren, P.,Falahat, S.,Nord, A.,Joensson, A.,Lake, I.,Doeoes, K.,Hieronymus, M.,Dietze, H.,Loeptien, U.,Kuznetsov, I.,Westerlund, A.,Tuomi, L.,Haapala, J. %D 2019 %J Geoscientific Model Development %N 1 %P 363-386 %R doi:10.5194/gmd-12-363-2019 %T Nemo-Nordic 1.0: A NEMO based ocean model for Baltic & North Seas, research and operational applications %U https://doi.org/10.5194/gmd-12-363-2019 1 %X We present Nemo-Nordic, a Baltic & North Sea model based on the NEMO ocean engine. Surrounded by highly industrialised countries, the Baltic and North seas, and their assets associated with shipping, fishing and tourism; are vulnerable to anthropogenic pressure and climate change. Ocean models providing reliable forecasts, and enabling climatic studies, are important tools for the shipping infrastructure and to get a better understanding of effects of climate change on the marine ecosystems. Nemo-Nordic is intended to come as a tool for both short term and long term simulations, and to be used for ocean forecasting as well as process and climatic studies. Here, the scientific and technical choices within Nemo-Nordic are introduced, and the reasons behind the design of the model and its domain, and the inclusions of the two seas, are explained. The model's ability to represent barotropic and baroclinic dynamics, as well as the vertical structure of the water column, is presented. Biases are shown and discussed. The short term capabilities of the model are presented, and especially its capabilities to represent sea level on an hourly timescale with a high degree of accuracy. We also show that the model can represent longer time scale, with a focus on the Major Baltic Inflows and the variability of deep water salinity in the Baltic Sea. %0 journal article %@ 1422-0067 %A Jung, O.,Smeets, R.,Hartjen, P.,Schnettler, R.,Feyerabend, F.,Klein, M.,Wegner, N.,Walther, F.,Stangier, D.,Henningsen, A.,Redenbach, C.,Heiland, M.,Barbeck, M.,Kopp, A. %D 2019 %J International Journal of Molecular Sciences %N 2 %P 255 %R doi:10.3390/ijms20020255 %T Improved In Vitro Test Procedure for Full Assessment of the Cytocompatibility of Degradable Magnesium Based on ISO 10993-5/-12 %U https://doi.org/10.3390/ijms20020255 2 %X Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations. %0 journal article %@ 1386-0291 %A Reinthaler, M.,Jung, F.,Empen, K. %D 2019 %J Clinical Hemorheology and Microcirculation %N 4 %P 381-389 %R doi:10.3233/CH-189303 %T Remote ischemic preconditioning of the heart: Combining lower limb ischemia and electronic stimulation oft he gastrocnemius muscle %U https://doi.org/10.3233/CH-189303 4 %X BACKGROUND:,Remote ischemic preconditioning (RIPC) has been demonstrated to induce potent cardioprotection in individuals experiencing coronary ischemia. A protocol combining limb ischemia and electronic muscle stimulation of the ischemic skeletal muscle (RIPC+), performed in advance of coronary artery occlusion, was superior in terms of infarct size reduction when compared to RIPC alone.,METHODS:,This study was performed to evaluate the benefit of RIPC + in humans compared to a standard RIPC protocol and a control group. Patients with a single vessel coronary artery disease undergoing elective PCI were eligible to participate in this study. ST-segment elevations from an intracoronary ECG during 3 brief episodes of coronary artery balloon occlusions/dilatation were used as the primary endpoint.,RESULTS:,ST-elevations significantly declined from the first to the third angioplasty in the control but remained at the same level in the RIPC and RIPC+groups. The RIPC group was characterized by the lowest ST-segment shift during coronary ischemia, which was comparable to coronary balloon occlusion number 3 in the control group, indicating successful preconditioning by the conventional RIPC method. In contrast, ST segment elevations were significantly higher in the RIPC + group. Troponin levels taken 24 h after the study procedure were significantly lower in the RIPC when compared to the control and the RIPC + group. %0 journal article %@ 1386-0291 %A Krüger-Genge, A.,Dietze, S.,Yan, W.,Liu, Y.,Fang, L.,Kratz, K.,Lendlein, A.,Jung, F. %D 2019 %J Clinical Hemorheology and Microcirculation %N 4 %P 511-529 %R doi:10.3233/CH-189317 %T Endothelial cell migration, adhesion and proliferation on different polymeric substrates %U https://doi.org/10.3233/CH-189317 4 %X BACKGROUND:,The formation of a functionally-confluent endothelial cell (EC) monolayer affords proliferation of EC, which only happens in case of appropriate migratory activity.,AIM OF THE STUDY:,The migratory pathway of human umbilical endothelial cells (HUVEC) was investigated on different polymeric substrates.,MATERIAL AND METHODS:,Surface characterization of the polymers was performed by contact angle measurements and atomic force microscopy under wet conditions. 30,000 HUVEC per well were seeded on polytetrafluoroethylene (PTFE) (θadv = 119°±2°), on low-attachment plate LAP (θadv = 28°±2°) and on polystyrene based tissue culture plates (TCP, θadv = 22°±1°). HUVEC tracks (trajectories) were recorded by time lapse microscopy and the euclidean distance (straight line between starting and end point), the total distance and the velocities of HUVEC not leaving the vision field were determined.,RESULTS:,On PTFE, 42 HUVEC were in the vision field directly after seeding. The mean length of single migration steps (SML) was 6.1±5.2 μm, the mean velocity (MV) 0.40±0.3 μm·min-1 and the complete length of the trajectory (LT) was 710±440 μm. On TCP 82 HUVEC were in the vision field subsequent to seeding. The LT was 840±550 μm, the SML 6.1±5.2 μm and the MV 0.44±0.3 μm·min-1. The trajectories on LAP differed significantly in respect to SML (2.4±3.9 μm, p < 0.05), the MV (0.16±0.3 μm·min-1, p < 0.05) and the LT (410±300 μm, p < 0.05), compared to PTFE and TCP. Solely on TCP a nearly confluent EC monolayer developed after three days. While on TCP diffuse signals of vinculin were found over the whole basal cell surface organizing the binding of the cells by focal adhesions, on PTFE vinculin was merely arranged at the cell rims, and on the hydrophilic material (LAP) no focal adhesions were found.,CONCLUSION:,The study revealed that the wettability of polymers affected not only the initial adherence but also the migration of EC, which is of importance for the proliferation and ultimately the endothelialization of polymer-based biomaterials. %0 conference lecture %@ %A Krueger-Genge, A.,Fuhrmann, R.,Franke, R.-P.,Jung, F. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T Effect of lipopolysaccharide on the adherence of human umbilical vein endothelial cells (HUVEC) on a natural substrate %U %X %0 book part %@ %A Braune, S.,Lendlein, A.,Jung, F. %D 2018 %J Hemocompatibility of Biomaterials for Clinical Applications, Blood-Biomaterials Interactions %N %P 51-76 %R doi:10.1016/B978-0-08-100497-5.00004-5 %T Developing standards and test protocols for testing the hemocompatibility of biomaterials %U https://doi.org/10.1016/B978-0-08-100497-5.00004-5 %X In this chapter, we have emphasized that the standards given by regulatory institutions, such as the ASTM or the ISO norm committee, describe only minimum requirements for studying the thrombogenicity and hemocompatibility of biomaterials. As a consequence, it is still under debate as to which supplementary assays need to be performed to enhance our understanding of the processes at the blood-material interface and to improve the hemocompatibility of new materials for blood-contacting implants. Test for the evaluation of thrombogenicity and hemocompatibility should at least be selected according to the categories formulated in the ISO norm: platelet adhesion and activation, coagulation, thrombosis, hematology, and immunology. In an ideal testing scenario, the selection of all above mentioned parameters should enable a comprehensive interstudy and interlaboratory comparison for different tested materials. Formulation of appropriate standards that allow reproducible testing and harmonized categorization of biomaterials should be consequently approached as a common consensus not just of the regulatory but also of the scientific community as it is already realized in the clinical chemistry and hematology. %0 conference lecture %@ %A Kuhnla, A.,Baeckemo-Johansson, J.,Maier, A.,Reinthaler, M.,Landmesser, U.,Lendlein, A.,Jung, F. %D 2018 %J 37. Jahrestagung Deutsche Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T In vitro hemocompatibility testing of left atrial appendage occlusion devices %U %X %0 journal article %@ 1386-0291 %A Jung, F.,Franke, F.-P. %D 2018 %J Clinical Hemorheology and Microcirculation %N 1 %P 1-3 %R doi:10.3233/CH-189900 %T Obituary: In memory of Prof. Dr. Holger Schmid-Schoenbein %U https://doi.org/10.3233/CH-189900 1 %X No abstract %0 journal article %@ 1386-0291 %A Al-Hindwan, H.S.A.,Landmesser, U.,Staehli, B.,Alushi, B.,Curio, J.,Neumann, T.,Jung, F.,Lendlein, A.,Jacobs, S.,Reinthaler, M. %D 2018 %J Clinical Hemorheology and Microcirculation %N 1 %P 15-25 %R doi:10.3233/CH-189906 %T The predictive value of a modified Carpentier classification in patients with coincidental mitral regurgitation undergoing TAVI for severe aortic valve stenosis %U https://doi.org/10.3233/CH-189906 1 %X INTRODUCTION:,Concomitant mitral-regurgitation (MR) is frequently observed in patients undergoing trans-catheter aortic valve implantation (TAVI). The predictive value of MR etiology remains to be elucidated.,METHODS:,600 patients with coincidental MR (≥moderate) undergoing TAVI were categorized according to a modified Carpentier classification [Groups: no/mild MR, n = 477; left atrial (LA) functional MR, n = 18; MR due to left ventricular dilatation, n = 29; degenerative MR, n = 50; MR with restricted leaflet motion n = 26]. MR improvement and patient outcome was compared among the groups in a retrospective analysis.,RESULTS:,MR regression was most pronounced in patients with restricted leaflet motion after 6 months, although a significant improvement was observed in all subgroups. MR relief was predominantly observed within the first 30 days after TAVI. Only patients with restricted leaflet motion experienced further improvement thereafter.,In the entire cohort a total of 15 strokes (2.5%) during the first 30 days after TAVI were observed, with the highest incidence in the LA functional cohort (3 events, 17%; p = 0.008). In multivariate analysis, organic etiology was associated with an increased 1-year mortality.,In conclusion, despite significant MR regression in all MR groups, some individuals may require additional mitralvalve repair after TAVI. According to our data the timing of these procedures should be based on the underlying MR etiology. The Carpentier classification in patients with coincidental MR undergoing TAVI for severe AS may also have prognostic implications as we found an increased incidence of strokes in our LA functional cohort and a worse mortality rates in organic MR. %0 journal article %@ 1386-0291 %A Krueger-Genge, A.,Braune, S.,Walter, M.,Krengel, M.,Kratz, K.,Kuepper, J.-H.,Lendlein, A.,Jung, F. %D 2018 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 305-316 %R doi:10.3233/CH-189130 %T Influence of different surface treatments of poly(Eta-butyl acrylate) networks on fibroblasts adhesion, morphology and viability %U https://doi.org/10.3233/CH-189130 1-2 %X BACKGROUND:,Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts.,MATERIAL AND METHODS:,Two types of cPnBA networks with Young’s moduli of 0.19±0.01 MPa (cPnBA04) and 1.02±0.01 MPa (cPnBA73) were synthesized and post-modified using oxygen plasma treatment (OPT) or fibrinogen coating (FIB) or a combination of both (OPT+FIB). The water contact angles of the differently post-treated cPnBAs were studied to monitor changes in the wettability of the polymer surfaces. Because of the key role of vascular fibroblasts in regeneration processes around implant materials, here we selected L929 fibroblasts as model cell type to explore morphology, viability, metabolic activity, cell membrane integrity as well as characteristics of the focal adhesions and cell cytoskeleton on the cPnBA surfaces.,RESULTS:,Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p < 0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743±434 cells·mm-2, was about 6.5 times higher than on cPnBA73 with 115±73 cells·mm-2. On cPnBA04 about 20% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBA networks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA.,CONCLUSION:,The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment. %0 journal article %@ 1386-0291 %A Gori, T.,Jung, F. %D 2018 %J Clinical Hemorheology and Microcirculation %N 4 %P 331-332 %R doi:10.3233/-189902 %T Obituary: In memory of Prof. Dr. Sandro Forconi %U https://doi.org/10.3233/-189902 4 %X No abstract %0 journal article %@ 1386-0291 %A Krueger-Genge, A.,Steinbrecht, S.,Kuepper, J.-H.,Lendlein, A.,Jung, F. %D 2018 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 267-276 %R doi:10.3233/CH-189125 %T Evidence for cytostatic effect of cyclophosphamide on human vein endothelial cells in cancer therapy: Preliminary in vitro results %U https://doi.org/10.3233/CH-189125 1-2 %X In cancer therapy, a number of drugs with different mechanisms of action are in clinical use, which act directly after administration without metabolism, while others only become active in the metabolites produced in the liver. Such drugs/metabolites – especially when administered parenterally – interact in high concentrations with the endothelium. Whether this induces adverse responses of the endothelial cells (EC) is barely studied for many medicaments.,This pilot in vitro study revealed that the addition of cyclophosphamide (CPA) to the culture medium (5 or 10 mM, respectively) showed a clear influence on EC compared to non-treated EC: The number of adherent human vein endothelial cells (HUVEC) decreased by the addition of CPA in a concentration-dependent manner compared to the untreated control, whereby the vitality of adherent cells was not affected. In addition, concomitant with activation of the adherent HUVEC, increased migratory activity occurred.,These results are in agreement with clinical events like thromboses in patients in compromised condition under therapy with CPA, as the detachment of EC might induce responses of circulating platelets leading to the adherence and aggregation with the risk of the formation of thrombi. Whether CPA acts directly or via toxic metabolites on EC will be examined in more detail in following studies. %0 conference lecture %@ %A Maier, A.,Braune, S.,Kratz, K.,Latour, R.A.,Lendlein, A.,Jung, F. %D 2018 %J 37. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie, DGKMH 2018 %N %P %T Adsorption and conformation of von Willebrand factor from fresh human plasma on to polymer-based biomaterials %U %X %0 journal article %@ 0002-8703 %A Reinthaler, M.,Ozga, A.-K.,Sinning, D.,Curio, J.,Al-Hindwan, H.S.,Baeckemo-Johansson, J.,Jung, F.,Lendlein, A.,Rauch, G.,Landmesser, U. %D 2018 %J American Heart Journal %N %P 95-102 %R doi:10.1016/j.ahj.2018.03.025 %T Revival of transcatheter PFO closure: A meta-analysis of randomized controlled trials - impact of shunt size and age %U https://doi.org/10.1016/j.ahj.2018.03.025 %X Background,Transcatheter foramen ovale closure (TPC) has emerged as a potential treatment option for patients with cryptogenic strokes and persistent foramen ovale (PFO). However, previous randomized controlled trials could hardly demonstrate any benefit compared to medical treatment (Med-Tx). Recently new data have become available which may change current practice of transcatheter PFO closure.,Methods,A systematic review and meta-analysis comparing TPC and Med-Tx based on all available multicentric randomized controlled trials was performed. The primary outcome of interest was the recurrence of stroke in both groups.,Results,Five studies met the inclusion criteria with 1829 patients in the TPC and 1622 in the Med-Tx group. The median follow-up was 4 years. In the intention-to-treat analysis we found a statistically significant relative risk reduction in recurrence of strokes in the TPC group compared to the Med-Tx group (pooled hazard ratio (HR): 0.32; 95% CI: 0.13–0.8; P = .018). Excluding one study due to potential publication bias resulted in a pooled HR of 0.48 (95% CI: 0.25–0.91, P = .024). Patients younger than 45 years of age (pooled HR: 0.35; 95% CI: 0.16–0.75; P = .007) and those with moderate to severe shunt (pooled HR: 0.28; 95% CI: 0.14–0.55; P < .001) were more likely to benefit from closure.,Conclusion,According to our meta-analysis TPC plus antiplatelets was superior in terms of stroke prevention when compared to Med-Tx. Furthermore, patients with moderate to severe shunts and those younger than 45 years of age were found to benefit most from TPC. %0 journal article %@ 1386-0291 %A Krueger-Genge, A.,Schulz, C.,Kratz, K.,Lendlein, A.,Jung, F. %D 2018 %J Clinical Hemorheology and Microcirculation %N 3 %P 437-445 %R doi:10.3233/CH-189904 %T Comparison of two substrate materials used as negative control in endothelialization studies: Glass versus polymeric tissue culture plate %U https://doi.org/10.3233/CH-189904 3 %X The endothelialization of synthetic surfaces applied as cardiovascular implant materials is an important issue to ensure the anti-thrombotic quality of a biomaterial. However, the rapid and constant development of a functionally-confluent endothelial cell monolayer is challenging. In order to investigate the compatibility of potential implant materials with endothelial cells several in vitro studies are performed. Here, glass and tissue culture plates (TCP) are often used as reference materials for in vitro pre-testing. However, a direct comparison of both substrates is lacking.,Therefore, a comparison of study results is difficult, since results are often related to various reference materials. In this study, the endothelialization of glass and TCP was investigated in terms of adherence, morphology, integrity, viability and function using human umbilical vein endothelial cells (HUVEC).,On both substrates an almost functionally confluent HUVEC monolayer was developed after nine days of cell seeding with clearly visible cell rims, decreased stress fiber formation and a pronounced marginal filament band. The viability of HUVEC was comparable for both substrates nine days after cell seeding with only a few dead cells. According to that, the cell membrane integrity as well as the metabolic activity showed no differences between TCP and glass. However, a significant difference was observed for the secretion of IL-6 and IL-8. The concentration of both cytokines, which are associated with migratory activity, was increased in the supernatant of HUVEC seeded on TCP. This result matches well with the slightly increased number of adherent HUVEC on TCP.,In conclusion, these findings indicate that both reference materials are almost comparable and can be used equivalently as control materials in in vitro endothelialization studies. %0 conference lecture %@ %A Reinthaler, M.,Baeckemo-Johansson, J.,Braune, S.,Al-Hindwan, H.S.A.,Lendlein, A.,Jung, F. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T Shear-induced platelet adherence and activation in an in-vitro dynamic multiwell-plate system %U %X %0 editorial %@ 1386-0291 %A Jung, F.,Connes, P.,Lehmann, C. %D 2018 %J Clinical Hemorheology and Microcirculation %N 4 %P 333-334 %R doi:10.3233/CH-189901 %T Editorial: A.L. Copley Best Paper Prize 2017 %U https://doi.org/10.3233/CH-189901 4 %X No abstract %0 conference lecture %@ %A Shin, E.-S.,Park, S.G.,Saleh, A.,Lam, Y.-Y.,Bhak, J.,Jung, F.,Morita, S.,Brachmann, J. %D 2018 %J 37. Jahrestagung Deutsche Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Magnetocardiography scoring system to predict the presence of obstructive coronary artery disease %U %X %0 conference poster %@ %A Baeckemo-Johansson, J.,Reinthaler, M.,Braune, S.,Lendlein, A.,Jung, F. %D 2018 %J International Biotech Innovation Days, IBID %N %P %T Shear-induced platelet adherence and activation in a dynamic multiwell-plate system %U %X %0 conference lecture %@ %A Mrowietz, C.,Franke, R.P.,Pindur, G.,Sternitzky, R.,Jung, F.,Wolf, U. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T Evaluation of Laser-Doppler-Fluxmetry for the diagnosis of microcirculatory disorders %U %X %0 conference lecture %@ %A Kuhnla, A.,Braune, S.,Baeckemo-Johannsson, J.,Maier, A.,Reinthaler, M.,Landmesser, U.,Lendlein, A.,Jung, F. %D 2018 %J 37. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie, DGKMH 2018 %N %P %T In vitro hemocompatibility testing of left atrial appendage occlusion device %U %X %0 conference lecture %@ %A da Silva, N.P.B.,Jung, E.M.,Jung, F.,Schlitt, H.J.,Hornung, M. %D 2018 %J 37. Jahrestagung Deutsche Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T VueBox® perfusion analysis of Contrast-Enhanced Ultrasound (CEUS) examinations in patients with primary hyperparathyroidism for preoperative detection of parathyroid gland adenoma %U %X %0 conference lecture %@ %A Braune, S.,Xourida, M.,Maier, A.,Kratz, K.,Latour, B.,Lendlein, A.,Jung, F. %D 2018 %J 37. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie, DGKMH 2018 %N %P %T Translocation and release of von Willebrand factor in platelets adherent on polymer-based biomaterial surfaces %U %X %0 conference lecture %@ %A Franke, R.-P.,Jung, F. %D 2018 %J 37. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie, DGKMH 2018 %N %P %T Effects of Iodinated contrast media on the microcirculation %U %X %0 conference lecture %@ %A Krueger-Genge, A.,Dietze, S.,Yan, W.,Liu, Y.,Fang, L.,Kratz, K.,Lendlein, A.,Jung, F. %D 2018 %J 37. Jahrestagung Deutsche Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Endothelial cell migration, adhesion and proliferation on different polymeric substrates %U %X %0 conference lecture %@ %A Reinthaler, M.,Jung, F.,Empen, K. %D 2018 %J 37. Jahrestagung Deutsche Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Remote ischemic preconditioning of the heart: Combining lower limb ischemia and electronic stimulation of the gastrocnemius muscle %U %X %0 journal article %@ 1386-0291 %A Hiebl, B.,Ascher, L.,Luetzow, K.,Kratz, K.,Gruber, C.,Mrowietz, C.,Nehring, M.E.,Lendlein, A.,Franke, R.-P.,Jung, F. %D 2018 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 317-326 %R doi:10.3233/CH-189108 %T Albumin solder covalently bound to a polymer membrane: New approach to improve binding strength in laser tissue soldering in-vitro %U https://doi.org/10.3233/CH-189108 1-2 %X Laser tissue soldering (LTS) based on indocyanine green (ICG)-mediated heat-denaturation of proteins might be a promising alternative technique for micro-suturing, but up to now the problem of too weak shear strength of the solder welds in comparison to sutures is not solved. Earlier reports gave promising results showing that solder supported by carrier materials can enhance the cohesive strength of the liquid solder. In these studies, the solder was applied to the carriers by dip coating. Higher reliability of the connection between the solder and the carrier material is expected when the solder is bound covalently to the carrier material. In the present study a poly(ether imide) (PEI) membrane served as carrier material and ICG-supplemented albumin as solder substrate. The latter was covalently coupled to the carrier membrane under physiological conditions to prevent structural protein changes. As laser source a diode continuous-wave laser emitting at 808 nm with intensities between 250 mW and 1500 mW was utilized. The albumin functionalized carrier membrane was placed onto the tunica media of explanted pig thoracic aortae forming an overlapping area of approximately 0.5×0.5 cm2. All tests were performed in a dry state to prevent laser light absorption by water. Infrared spectroscopy, spectro-photometrical determination of the secondary and primary amine groups after acid orange II staining, contact angle measurements, and atomic force microscopy proved the successful functionalization of the PEI membrane with albumin. A laser power of 450 mW LTS could generate a membrane-blood vessel connection which was characterized by a shear strength of 0.08±0.002 MPa, corresponding to 15% of the tensile strength of the native blood vessel. Theoretically, an overlapping zone of 4.1 mm around the entire circumference of the blood vessel could have provided shear strength of the PEI membrane-blood vessel compound identical to the tensile strength of the native blood vessel. These in-vitro results confirmed the beneficial effects of solder reinforcement by carrier membranes, and suggest LTS with covalently bound solders on PEI substrates for further studies in animal models. %0 conference lecture %@ %A Braune, S.,Sperling, C.,Maitz, M.F.,Steinseifer, U.,Clauser, J.,Hiebl, B.,Krajewski, S.,Wendel, H.P.,Jung, F. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T Thrombogenicity testing of polymers: round-robin study to assess inter-center variability %U %X %0 editorial %@ 2352-3697 %A Roediger, S.,Kammerer, S.,Schmailzl, K.J.G.,Kuepper, J.-H.,Jung, F. %D 2018 %J Journal of Cellular Biotechnology %N 1-2 %P 1-3 %R doi:10.3233/JCB-189001 %T Editorial %U https://doi.org/10.3233/JCB-189001 1-2 %X No abstract %0 conference lecture %@ %A Kuhnla, A.,Reinthaler, M.,Braune, S.,Maier, A.,Pindur, G.,Lendlein, A.,Jung, F. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age %U %X %0 journal article %@ 2045-2322 %A Mohammadi-Aragh, M.,Goessling, H.,Losch, M.,Hutter, N.,Jung, T. %D 2018 %J Scientific Reports %N %P 6514 %R doi:10.1038/s41598-018-24660-0 %T Predictability of Arctic sea ice on weather time scales %U https://doi.org/10.1038/s41598-018-24660-0 %X The field of Arctic sea ice prediction on “weather time scales” is still in its infancy with little existing understanding of the limits of predictability. This is especially true for sea ice deformation along so-called Linear Kinematic Features (LKFs) including leads that are relevant for marine operations. Here the potential predictability of the sea ice pack in the wintertime Arctic up to ten days ahead is determined, exploiting the fact that sea ice-ocean models start to show skill at representing sea ice deformation at high spatial resolutions. Results are based on ensemble simulations with a high-resolution sea ice-ocean model driven by atmospheric ensemble forecasts. The predictability of LKFs as measured by different metrics drops quickly, with predictability being almost completely lost after 4–8 days. In contrast, quantities such as sea ice concentration or the location of the ice edge retain high levels of predictability throughout the full 10-day forecast period. It is argued that the rapid error growth for LKFs is mainly due to the chaotic behaviour of the atmosphere associated with the low predictability of near surface wind divergence and vorticity; initial condition uncertainty for ice thickness is found to be of minor importance as long as LKFs are initialized at the right locations. %0 conference lecture %@ %A Papagrigorakes, M.,Chirico, N.,Blocki, A.,Neffe, A.T.,Jung, F.,Ma, N.,Lendlein, A. %D 2018 %J Joint Conference of Three Societies: European Society of Clinical Hemorheology and Miclrocirculation, International Society of Biorheology, International Society of Clinical Hemorheology, ESCHM-ISB-ISCH 2018 %N %P %T AD-MSCS change their morphology and secretion profile as a response to changes in substrates`elastic properties in combination with inflammatory stimuli %U %X %0 journal article %@ 1386-0291 %A Felthaus, O.,Schoen, T.,Schiltz, D.,Aung, T.,Kuehlmann, B.,Jung, F.,Anker, A.,Klein, S.,Prantl, L. %D 2018 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 141-151 %R doi:10.3233/CH-189107 %T Adipose tissue-derived stem cells from affected and unaffected areas in patients with multiple symmetric lipomatosis show differential regulation of mTOR pathway genes %U https://doi.org/10.3233/CH-189107 1-2 %X BACKGROUND:,Multiple symmetric lipomatosis is a rare disease characterized by the excessive growth of uncapsulated masses of adipose tissue. Although the etiology has yet to be elucidated, a connection to brown adipose tissue has been proposed recently. The mTOR pathway which is found to be regulated in lipomatous tissue as well as associated with brown adipose tissue can be inhibited by a compound called rapamycin.,METHODS:,We isolated adipose tissue derived stem cells from both affected and unaffected tissue and treated these cells with different concentrations of rapamycin.,RESULTS:,The differences in both proliferation and differentiation between adipose tissue derived stem cells (ASCs) from lipomatous and normal tissue decreased after mTOR pathway inhibition. In some patients regulation of mTOR genes was opposed in the ASCs from the two different tissues.,CONCLUSIONS:,Treatment with rapamycin might be a novel therapeutical approach for patients suffering from multiple symmetric lipomatosis. %0 editorial %@ 1386-0291 %A Jung, E.M.,Jung, F.,Xu, H.-X. %D 2017 %J Clinical Hemorheology and Microcirculation %N 4 %P 273-275 %R doi:10.3233/CH-179100 %T Editorial: Developments in the application of high resolution ultrasound in clinical diagnostics %U https://doi.org/10.3233/CH-179100 4 %X No abstract %0 journal article %@ 1042-7147 %A Blocki, A.,Loewenberg, C.,Jiang, Y.,Kratz, K.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2017 %J Polymers for Advanced Technologies %N 10 %P 1245-1251 %R doi:10.1002/pat.3947 %T Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties %U https://doi.org/10.1002/pat.3947 10 %X Gelatin-based hydrogels offer various biochemical cues that support encapsulated cells and are therefore suitable as cell delivery vehicles in regenerative medicine. However, besides the biochemical signals, biomechanical cues are crucial to ensure an optimal support of encapsulated cells. Hence, we aimed to correlate the cellular response of encapsulated cells to macroscopic and microscopic elastic properties of glycidylmethacrylate (GMA)-functionalized gelatin-based hydrogels. To ensure that different observations in cellular behavior could be attributed to differences in elastic properties, an identical concentration as well as degree of functionalization of biopolymers was utilized to form covalently crosslinked hydrogels. Elastic properties were merely altered by varying the average gelatin-chain length. Hydrogels exhibited an increased degree of swelling and a decreased bulk elastic modulus G′ with prolonged autoclaving of the starting solution. This was accompanied by an increase of hydrogel mesh size and thus by a reduction of crosslinking density. Tougher hydrogels retained the largest amount of cells; however, they also interfered with cell viability. Softer gels contained a lower cell density, but supported cell elongation and viability. Observed differences could be partially attributed to differences in bulk properties, as high crosslinking densities interfere with diffusion and cell spreading and thus can impede cell viability. Interestingly, a microscopic elastic modulus in the range of native soft tissue supported cell viability and elongation best while ensuring a good cell entrapment. In conclusion, gelatin-based hydrogels providing a soft tissue-like microenvironment represent adequate cell delivery vehicles for tissue engineering approaches. %0 journal article %@ 0268-960X %A Reviakine, I.,Jung, F.,Braune, S.,Brash, J.L.,Latour, R.,Gorbet, M.,Oeveren, W.van %D 2017 %J Blood Reviews %N 1 %P 11-21 %R doi:10.1016/j.blre.2016.07.003 %T Stirred, shaken, or stagnant: What goes on at the blood-biomaterial interface %U https://doi.org/10.1016/j.blre.2016.07.003 1 %X There is a widely recognized need to improve the performance of vascular implants and external medical devices that come into contact with blood by reducing adverse reactions they cause, such as thrombosis and inflammation. These reactions lead to major adverse cardiovascular events such as heart attacks and strokes. Currently, they are managed therapeutically. This need remains unmet by the biomaterials research community. Recognized stagnation of the blood–biomaterial interface research translates into waning interest from clinicians, funding agencies, and practitioners of adjacent fields. The purpose of this contribution is to stir things up. It follows the 2014 BloodSurf meeting (74th International IUVSTA Workshop on Blood–Biomaterial Interactions), offers reflections on the situation in the field, and a three-pronged strategy integrating different perspectives on the biological mechanisms underlying blood–biomaterial interactions. The success of this strategy depends on reengaging clinicians and on the renewed cooperation of the funding agencies to support long-term efforts. %0 editorial %@ 1386-0291 %A Jung, F.,Connes, P.,Lehmann, C. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3 %P 185-186 %R doi:10.3233/CH-179000 %T Editorial: A.L. Copley Best Paper Prize 2016 %U https://doi.org/10.3233/CH-179000 3 %X No abstract %0 journal article %@ 2192-2640 %A Braune, S.,Latour, R.A.,Lendlein, A.,Jung, F. %D 2017 %J Advanced Healthcare Materials %N 17 %P 1700294 %R doi:10.1002/adhm.201700294 %T Comment on: “Hemocompatibility of Superhemophobic Titania Surfaces” %U https://doi.org/10.1002/adhm.201700294 17 %X No abstract %0 journal article %@ 1549-3296 %A Klopfleisch, R.,Jung, F. %D 2017 %J Journal of Biomedical Materials Research A %N 3 %P 927-940 %R doi:10.1002/jbm.a.35958 %T The pathology of the foreign body reaction against biomaterials %U https://doi.org/10.1002/jbm.a.35958 3 %X The healing process after implantation of biomaterials involves the interaction of many contributing factors. Besides their in vivo functionality, biomaterials also require characteristics that allow their integration into the designated tissue without eliciting an overshooting foreign body reaction (FBR). The targeted design of biomaterials with these features, thus, needs understanding of the molecular mechanisms of the FBR. Much effort has been put into research on the interaction of engineered materials and the host tissue. This elucidated many aspects of the five FBR phases, that is protein adsorption, acute inflammation, chronic inflammation, foreign body giant cell formation, and fibrous capsule formation. However, in practice, it is still difficult to predict the response against a newly designed biomaterial purely based on the knowledge of its physical–chemical surface features. This insufficient knowledge leads to a high number of factors potentially influencing the FBR, which have to be analyzed in complex animal experiments including appropriate data-based sample sizes. This review is focused on the current knowledge on the general mechanisms of the FBR against biomaterials and the influence of biomaterial surface topography and chemical and physical features on the quality and quantity of the reaction. %0 journal article %@ 0927-7765 %A Braune, S.,Sperling, C.,Maitz, M.F.,Steinseifer, U.,Clauser, J.,Hiebl, B.,Krajewski, S.,Wendel, H.P.,Jung, F. %D 2017 %J Colloids and Surfaces B %N %P 416-422 %R doi:10.1016/j.colsurfb.2017.06.053 %T Evaluation of platelet adhesion and activation on polymers: Round-robin study to assess inter-center variability %U https://doi.org/10.1016/j.colsurfb.2017.06.053 %X The regulatory agencies provide recommendations rather than protocols or standard operation procedures for the hemocompatibility evaluation of novel materials e.g. for cardiovascular applications. Thus, there is a lack of specifications with regard to test setups and procedures. As a consequence, laboratories worldwide perform in vitro assays under substantially different test conditions, so that inter-laboratory and inter-study comparisons are impossible. Here, we report about a prospective, randomized and double-blind multicenter trial which demonstrates that standardization of in vitro test protocols allows a reproducible assessment of platelet adhesion and activation from fresh human platelet rich plasma as possible indicators of the thrombogenicity of cardiovascular implants. Standardization of the reported static in vitro setup resulted in a laboratory independent scoring of the following materials: poly(dimethyl siloxane) (PDMS), poly(ethylene terephthalate) (PET) and poly(tetrafluoro ethylene) (PTFE). The results of this in vitro study provide evidence that inter-laboratory and inter-study comparisons can be achieved for the evaluation of the adhesion and activation of platelets on blood-contacting biomaterials by stringent standardization of test protocols. %0 journal article %@ 0167-5273 %A Shin, E.-S.,Lam, Y.-Y.,Her, A.-Y.,Brachmann, J.,Jung, F.,Park, J.-W. %D 2017 %J International Journal of Cardiology %N %P 948-952 %R doi:10.1016/j.ijcard.2016.11.165 %T Incremental diagnostic value of combined quantitative and qualitative parameters of magnetocardiography to detect coronary artery disease %U https://doi.org/10.1016/j.ijcard.2016.11.165 %X Background/objectives,Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. This study sought to investigate the incremental diagnostic value of combined quantitative and qualitative parameters of MCG to detect coronary artery disease (CAD).,Methods,Ninety six patients with suspected CAD who underwent coronary angiography were enrolled in the analysis to test the diagnostic accuracy of 2 MCG parameters (a quantitative parameter of the percent change of ST-segment fluctuation score and a qualitative parameter of non-dipole phenomenon).,Results,The best cut-off value for the percent change of ST-segment fluctuation score was − 51.0%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.1, 73.9, 82.0, 79.1, and 77.4, in the percent change of ST-segment fluctuation score and 86.5, 84.8, 88.0, 86.7, and 86.3 in non-dipole phenomenon. The area under the curve of receiver-operating characteristics was 0.79 for the percent change of ST-segment fluctuation score and 0.86 for non-dipole phenomenon (p < 0.001). However, the incorporation of non-dipole phenomenon into a model with the percent change of ST-segment fluctuation score significantly improved C-statistics, indicating the enhancement of diagnostic performance in the detection of significant CAD (0.790 to 0.930; p < 0.001).,Conclusions,Qualitative assessment of non-dipole phenomenon has a better diagnostic value than the quantitative parameter of percent change of ST-segment fluctuation score in the detection of significant CAD. Furthermore, this study found that the incorporation of non-dipole phenomenon into the percent change of ST-segment fluctuation score significantly improved the diagnostic performance of CAD detection. %0 conference lecture %@ %A Radjabian, M.,Clodt, J.,Jung, A.,Saleem, S.,Hoehme, C.,Keskin, D.,Dami, S.,Rangou, S.,Lademann, B.,Buhr, K.,Abetz, C.,Filiz, V.,Abetz, V.,Oss-Ronen, L.,Cohen, Y.,Talmon, Y.,Stegelemeier, C.,Foerster, S. %D 2017 %J 11th International Congress on Membranes and Membrane Processes, ICOM 2017 %N %P %T Block copolymer self-assembly: from solution to nanoporous membranes with tailored size pores %U %X %0 journal article %@ 1752-0894 %A Wang, J.,Yang, B.,Ljungqvist, F.C.,Luterbacher, J.,Osborn, T.J.,Briffa, K.R.,Zorita, E. %D 2017 %J Nature Geoscience %N %P 512-517 %R doi:10.1038/ngeo2962 %T Internal and external forcing of multidecadal Atlantic climate variability over the past 1,200 years %U https://doi.org/10.1038/ngeo2962 %X The North Atlantic experiences climate variability on multidecadal scales, which is sometimes referred to as Atlantic multidecadal variability. However, the relative contributions of external forcing such as changes in solar irradiance or volcanic activity and internal dynamics to these variations are unclear. Here we provide evidence for persistent summer Atlantic multidecadal variability from AD 800 to 2010 using a network of annually resolved terrestrial proxy records from the circum-North Atlantic region. We find that large volcanic eruptions and solar irradiance minima induce cool phases of Atlantic multidecadal variability and collectively explain about 30% of the variance in the reconstruction on timescales greater than 30 years. We are then able to isolate the internally generated component of Atlantic multidecadal variability, which we define as the Atlantic multidecadal oscillation. We find that the Atlantic multidecadal oscillation is the largest contributor to Atlantic multidecadal variability over the past 1,200 years. We also identify coherence between the Atlantic multidecadal oscillation and Northern Hemisphere temperature variations, leading us to conclude that the apparent link between Atlantic multidecadal variability and regional to hemispheric climate does not arise solely from a common response to external drivers, and may instead reflect dynamic processes. %0 journal article %@ 0894-8755 %A Buentgen, U.,Krusik, P.J.,Verstege, A.,Sanguesa Barreda, G.,Wagner, S.,Camarero, J.J.,Ljungqvist, F.C.,Zorita, E.,Oppenheimer, C.,Konter, O.,Tegel, W.,Gaertner, H.,Cherubini, P.,Reinig, F.,Esper, J. %D 2017 %J Journal of Climate %N 14 %P 5295-5318 %R doi:10.1175/JCLI-D-16-0526.1 %T New Tree-Ring Evidence from the Pyrenees Reveals Western Mediterranean Climate Variability since Medieval Times %U https://doi.org/10.1175/JCLI-D-16-0526.1 14 %X Paleoclimatic evidence is necessary to place the current warming and drying of the western Mediterranean basin in a long-term perspective of natural climate variability. Annually resolved and absolutely dated temperature proxies south of the European Alps that extend back into medieval times are, however, mainly limited to measurements of maximum latewood density (MXD) from high-elevation conifers. Here, we present the world’s best replicated MXD site chronology of 414 living and relict Pinus uncinata trees found >2200 m asl in the Spanish central Pyrenees. This composite record correlates significantly (p ≤0.01) with May-June and August-September mean temperatures over most of the Iberian Peninsula and northern Africa (r =0.72 1950-2014). Spanning the period 1186-2014 CE, the new reconstruction reveals overall warmer conditions around 1200 and 1400, and again after ~1850. The coldest reconstructed summer in 1258 (-4.4°C wrt 1961-1990) followed the largest known volcanic eruption of the CE. The 20th century is characterized by pronounced summer cooling in the 1970s, subsequently rising temperatures until 2003, and a slowdown of warming afterwards. Little agreement is found with climate model simulations that consistently overestimate recent summer warming and underestimate pre-industrial temperature changes. Interannual to multi-decadal co-variability with regional hydroclimate includes summer pluvials after large volcanic eruptions. Our study demonstrates the relevance of updating MXD-based temperature reconstructions, not only back in time but also towards the present, and emphasizes the importance of comparing temperature and hydroclimatic proxies, as well as model simulations for understanding regional climate dynamics. %0 journal article %@ 1932-6254 %A Haase, T.,Krost, A.,Sauter, T.,Kratz, K.,Peter, J.,Kamann, S.,Jung, F.,Lendlein, A.,Zohlnhöfer, D.,Rüder, C. %D 2017 %J Journal of Tissue Engineering and Regenerative Medicine %N 4 %P 1034-1044 %R doi:10.1002/term.2002 %T In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds %U https://doi.org/10.1002/term.2002 4 %X Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28 days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7–28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7 days after implantation and remained stable until 28 days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing. %0 journal article %@ 0167-7799 %A Hauser, S.,Jung, F.,Pietzsch, J. %D 2017 %J Trends in Biotechnology %N 3 %P 265-277 %R doi:10.1016/j.tibtech.2016.09.007 %T Human Endothelial Cell Models in Biomaterial Research %U https://doi.org/10.1016/j.tibtech.2016.09.007 3 %X Endothelial cell (EC) models have evolved as important tools in biomaterial research due to ubiquitously occurring interactions between implanted materials and the endothelium. However, screening the available literature has revealed a gap between material scientists and physiologists in terms of their understanding of these biomaterial–endothelium interactions and their relative importance. Consequently, EC models are often applied in nonphysiological experimental setups, or too extensive conclusions are drawn from their results. The question arises whether this might be one reason why, among the many potential biomaterials, only a few have found their way into the clinic. In this review, we provide an overview of established EC models and possible selection criteria to enable researchers to determine the most reliable and relevant EC model to use. %0 journal article %@ 1386-0291 %A Blocki, A.,Loeper, F.,Chirico, N.,Neffe, A.T.,Jung, F.,Stamm, C.,Lendlein, A. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 251-259 %R doi:10.3233/CH-179206 %T Engineering of cell-laden gelatin-based microcapsules for cell delivery and immobilization in regenerative therapies %U https://doi.org/10.3233/CH-179206 3-4 %X Cell-based therapies often face the challenge of low cell retention and viability upon transplantation. Hence, biomaterials, which can immobilize transplanted cells, while at the same time support cell viability, are essential for successful clinical application. Noteworthy, biomaterials in the micrometer range such as microcapsules have the advantage of a minimally invasive introduction into tissue.,Hence, we established an approach to generate gelatin-based cell carriers in the form of microspherical hydrogels. Fibroblasts were microencapsulated in glycidylmethacrylate (GMA)-functionalized gelatin by photopolymerization. While the degree of GMA-functionalization was kept constant, the hydrogel cross-linking density was adjusted by varying the time of irradiation, or the average gelatin-chain length.,Stable microcapsules could be achieved with 10 wt% GMA-gelatin solutions for all irradiation periods tested (0.5 –2 min). Evaluation of cell viability revealed that microgels with the same weight content of biopolymer but with decreased cross-linking densities and thus decreasing storage, and E moduli resulted in best cell support. Noteworthy, encapsulated cells partially migrated out of the microcapsules and attached to the spherical surface.,10 wt% GMA-gelatin-based hydrogels with E moduli properties comparable to the native cellular niche proved to be a promising biomaterial suitable for the production of cell-laden microcapsules and shall be evaluated further for biomedical application. %0 journal article %@ 1752-0894 %A Buentgen, U.,Myglan, V.S.,Ljungqvist, F.C.,McCormick, M.,Di Cosmo, N.,Sigl, M.,Jungclaus, J.,Wagner, S.,Krusic, P.J.,Esper, J.,kaplan, J.O.,de Vaan, M.A.C.,Luterbacher, J.,Wacker, L.,Tegel, W.,Solomina, O.N.,Nicolussi, K.,Oppenheimer, C.,Reinig, F.,Kirdyanov, A.V. %D 2017 %J Nature Geoscience %N %P 243 %R doi:10.1038/ngeo2927 %T Reply to 'Limited Late Antique cooling' %U https://doi.org/10.1038/ngeo2927 %X No abstract %0 journal article %@ 1386-0291 %A Krueger-Genge, A.,Hiebl, B.,Franke, R.P.,Lendlein, A.,Jung, F. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 309-318 %R doi:10.3233/CH-179211 %T Effects of Tacrolimus or Sirolimus on the adhesion of vascular wall cells: Controlled in-vitro comparison study %U https://doi.org/10.3233/CH-179211 3-4 %X In drug eluting stents the cytostatic drugs Sirolimus or Tacrolimus are used to inhibit blood vessel restenosis by limiting the proliferation of smooth muscle cells. However, the cytostatic activity of both drugs was shown to be not cell specific and could also affect the stent endothelialisation, respectively. Currently, only limited in vitro data are available about the impact of Sirolimus and Tacrolimus on endothelial cell proliferation over a broad concentration range. To answer this question the following study was performed.,Commercially obtained HUVEC were expanded with DMEM cell culture medium (GIBCO, Germany) supplemented with 5 vol% fetal calf serum on non-coated regular polystyrene-based 24-multiwell plates. For drug testings 2×104 cells/cm2 were seeded and grown for 24 h until 30–40% of the multiwell surfaces were covered and then exposed to Sirolimus (1.0×10–11–1.0×10–5 mol/l) or Tacrolimus (2.0×10–8–6.2×10–5 mol/l), both dissolved in DMSO. 12, 24 and 48 h after adding the drugs cell numbers per area were quantified by counting the cells in six wells with four fields of view per well, representing 0.6 mm2, using a confocal laser microscope.,After 48 h of cell growth in the drug-free cell culture medium, the HUVEC number increased from 2.0×104 to 3.55×104 cells/cm2 (mean cell doubling time: 53.6 h, n = 6). At lower concentrations (≤2.0×10–6 mol/l) Tacrolimus reduced the number of adherent HUVEC significantly less than Sirolimus (p < 0.05). However, at higher concentrations (≥2.07×10–5 mol/l) the effect of Tacrolimus on the number of adherent endothelial cells was significantly greater than that of Sirolimus (p < 0.05). At the highest concentration applied (6.22×10–5 mol/l), Tacrolimus induced detachment of all HUVECs within 12 h after drug application. The number of adherent HUVEC decreased only slightly (about 9%) after Sirolimus application at the highest concentration (1.09×10–5 mol/l).,These data show that in a non-flow model the cytostatic drug Tacrolimus reduced the number of adherent endothelial cells less than Sirolimus, as long as the drug concentration did not surpass 10–6 mol/l. At the limits of solubility, Sirolimus (1×10–5 mol/l) reduced the number of adherent endothelial cells less than Tacrolimus (6×10–5 mol/l), which induced detachment of endothelial cells. %0 journal article %@ 1386-0291 %A Mrowietz, C.,Franke, F.P.,Pindur, G.,Wolf, U.,Jung, F. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 347-353 %R doi:10.3233/CH-179215 %T Reference range and variability of Laser-Doppler-Fluxmetry %U https://doi.org/10.3233/CH-179215 3-4 %X The Laser Doppler technique, a noninvasive method to estimate skin blood flow (LDF), is frequently used in research and clinical routine [1]. Here, the measurements were carried out with a new Laser Doppler system, the DOPsystem, which allows to measure frequency spectra in four different frequency windows according to the velocities in venules (low velocity), capillaries (low to medium velocities), and in arteries (with high and very high velocities). However, the diagnostic reliability or the effectiveness of the LDF has not yet been evaluated sufficiently, which is indispensable, where medical diagnostics and therapy controls are concerned. For a valid interpretation of LDF values of individual patients, the knowledge of the reference range and the variability of the measured parameters is required.,In four successive studies the reference range (62 apparently healthy subjects), the circadian variability (8 subjects), the variability from day-to-day (6 subjects) and over one year with monthly measurements (6 subjects) were evaluated.,With the knowledge of the reference range, microcirculatory disorders can now be diagnosed with the DOP method used. Following a standard measurement procedure there was no dependence of the measured data on the day or season of measurement. %0 editorial %@ 1386-0291 %A Juenger, M.,Krueger-Genge, A.,Jung, F. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 209 %R doi:10.3233/CH-179200 %T Editorial: 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %U https://doi.org/10.3233/CH-179200 3-4 %X No abstract %0 journal article %@ 1386-0291 %A Lamby, P.,Prantl, L.Krueger-Genge, A.,Franke, R.P.,Jung, E.M.,Jung, F. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 211-214 %R doi:10.3233/CH-179201 %T Influence of Ultrasound Microbubbles on kidney oxygen tension %U https://doi.org/10.3233/CH-179201 3-4 %X Ultrasound contrast agents (USCA) allows the dynamic detection of blood flow of both the macro and microvasculature. An obvious prerequisite for USCAs is the unhindered passage of clinically relevant dose levels through the microcirculation especially of the lungue, where they have to pass capillaries with diameters of around 4 μm. While smaller microbubbles rapidly passed through the microcirculation along with the red blood cells, larger microbubbles, however, were observed to coalesce and interrupt the blood flow. Whether this might influence the tissue oxygen tension is unclear up to now.,To examine this question a bolus of 2.4 ml SonoVue™ was injected into the suprarenal aorta at a flow rate of 10 ml/s (a dosage usually applied in the clinic). The pO2 in the outer medulla of the kidney was continuously measured using a flexible pO2 microcatheter. In addition, the SonoVue™ injection and its passage through the renal vasculature were documented by the CEUS technology to assess whether the microbubbles passed the kidney.,The study revealed that SonoVue™ induced no changes of the mean oxygen partial pressure in the outer medulla which confirms that these microbubbles on their way through the medullar capillaries did not hinder the co-flow of blood through the renal microvessels in a big animal model with a renal morphology and function comparable to human kidneys. These results demonstrate that the CEUS diagnostic itself did not influence the system to be examined which is a most important prerequisite for any diagnostic method.,With the introduction of ultrasound contrast agents (USCA), diagnostic ultrasound has entered a new era that allows the dynamic detection of blood flow of both the macro and microvasculature [1]. USCAs are shell-coated gas-filled microbubbles that are administered to the systemic circulation. As there is a great difference in echogenicity between the gas in the microbubbles and the soft tissue of the body such microbubbles are used to image the vasculature as well as the blood flow in veins, arteries and also microvessels [2]. An obvious prerequisite for USCAs is the free, unhindered passage of clinically relevant dose levels through the microcirculation. So, microbubbles have to be able to pass capillaries with diameters of around 4 μm [3]. The mean diameter of the microbubbles of SonoVue™ (Bracco, Konstanz, Germany) was described to be 2.5 μm, and more than 90% of the bubbles are smaller than 8 μm [4]. Bigger bubbles traversing the capillary bed would have to deform and adapt their shape to the diameter of the capillaries. Feinstein et al. showed that the smaller microbubbles rapidly passed through the microcirculation along with the red blood cells. Larger microbubbles, however, were observed to coalesce and interrupt the blood flow (subsequently they collapse or shrink [5]). Up to now it is unclear, whether such USCA-induced drop of blood flow might impair the oxygen tension (pO2) in kidneys [6, 7]. The decisive question is, whether the rate of flow disturbance induced by the injection of SonoVue™ could become so relevant as to influence and limit the oxygen supply to the surrounding kidney tissue.,To examine whether an injection of SonoVue™ might influence the pO2 in the tissue of the downstream microcirculation, a bolus of 2.4 ml was injected into the suprarenal aorta at a flow rate of 10 ml/s (a dosage usually applied in the clinic [8]. It was immediately followed by 10 ml of isotonic sodium chloride solution. The pO2 in the outer medulla of the kidney was continuously measured using a flexible pO2 microcather [9]. SonoVue™ injection and its passage through the renal vasculature were documented by the CEUS technology to assess whether the microbubbles passed the kidney [9].,The Bavarian Institutional Animal Care and Use Committee approved the study protocol for the experiments performed in this study (AZ.: 54-2532.1-31/13). %0 conference lecture %@ %A Krueger-Genge, A.,Hiebl, B.,Franke, R.P.,Lendlein, A.,Jung, F. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Effects of Tacrolimus or Sirolimus on the adhesion of vascular wall cells: Controlled in-vitro comparison study %U %X %0 conference lecture %@ %A Blocki, A.,Loeper, F.,Chirico, N.,Neffe, A.T.,Jung, F.,Stamm, C.,Lendlein, A. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Engineering of cell-laden gelatin-based microcapsules for cell delivery and immobilization in regenerative therapies %U %X %0 conference lecture %@ %A Mrowietz, C.,Franke, F.P.,Pindur, G.,Wolf, U.,Jung, F. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Reference range and variability of Laser-Doppler-Fluxmetry %U %X %0 conference lecture %@ %A Lamby, P.,Prantl, L.Krueger-Genge, A.,Franke, R.P.,Jung, E.M.,Jung, F. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Influence of Ultrasound Microbubbles on kidney oxygen tension %U %X %0 conference lecture %@ %A Wang, W.,Li, W.,Wang, J.,Hu, Q.,Balk, M.,Bieback, K.,Stamm, C.,Jung, F.,Tang, G.,Lendlein, A.,Ma, N. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Folate receptor mediated genetic modification of human mesenchymal stem cells via folic acid-polyethylenimine-grafted poly(N-3-hydroxypropyl)aspartamide %U %X %0 conference lecture %@ %A Li, Z.,Xu, X.,Wang, W.,Kratz, K.,Sun, X.,Zou, J.,Deng, Z.,Jung, F.,Gossen, M.,Ma, N.,Lendlein, A. %D 2017 %J 36th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure %U %X %0 journal article %@ 1386-0291 %A Li, Z.,Xu, X.,Wang, W.,Kratz, K.,Sun, X.,Zou, J.,Deng, Z.,Jung, F.,Gossen, M.,Ma, N.,Lendlein, A. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 267-278 %R doi:10.3233/CH-179208 %T Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure %U https://doi.org/10.3233/CH-179208 3-4 %X Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells. %0 journal article %@ 2045-2322 %A Lamby, P.,Jung, F.,Graf, S.,Schellenberg, L.,Falter, J.,Platz-da-Silva, N.,Schreml, S.,Prantl, L.,Franke, R.P.,Jung, E.M. %D 2017 %J Scientific Reports %N %P 13125 %R doi:10.1038/s41598-017-13253-y %T Effect of iodinated contrast media on renal perfusion: A randomized comparison study in pigs using quantitative contrast-enhanced ultrasound (CEUS) %U https://doi.org/10.1038/s41598-017-13253-y %X The administration of iodinated contrast media (CM) can cause microcirculatory disorder leading to acute renal dysfunction. In a prospective, randomized investigation two CM (Iodixanol vs Iopromide) were compared in 16 pigs. Each animal received 10 intra-aortal injections (5 ml Iodixanol or 4.32 ml Iopromide). Microcirculation was assessed using contrast-enhanced ultrasound (CEUS) directly on the kidney surface using time-to-peak (TTP) and blood-volume-analysis. Macroscopic observations were documented. Post mortem residual CM distribution in the kidneys was detected using X-ray. TTP was significantly prolonged over the descending vasa recta of the Iopromide group. This coincided with a visible marble-like pattern on the kidney surface occurring in 30 out of 80 Iopromide-injections but in 4 out of 80 Iodixanol-injections (p = 0.007). The blood volume over the entire kidney did not change after Iodixanol-application, but decreased by about 6.1% after Iopromide-application. The regional blood volume in the renal cortex showed a tendency to decrease by about 13.5% (p = 0.094) after Iodixanol-application, and clearly decreased by about 31.7% (p = 0.022) after Iopromide-application. The study revealed a consistent influence of repeated injections of two different CM on the kidney perfusion using three different imaging methods (CEUS analysis, macroscopic observation and X-ray analysis). %0 journal article %@ 1386-0291 %A Wang, W.,Li, W.,Wang, J.,Hu, Q.,Balk, M.,Bieback, K.,Stamm, C.,Jung, F.,Tang, G.,Lendlein, A.,Ma, N. %D 2017 %J Clinical Hemorheology and Microcirculation %N 3-4 %P 279-295 %R doi:10.3233/CH-179209 %T Folate receptor mediated genetic modification of human mesenchymal stem cells via folic acid-polyethylenimine-grafted poly(N-3-hydroxypropyl)aspartamide %U https://doi.org/10.3233/CH-179209 3-4 %X Mesenchymal stem cells (MSCs) are targeted as vehicles for cell mediated gene therapy. Here we report on a macromolecular carrier, which was designed aiming at successful targeted gene delivery into MSCs through the mediation of folate receptor and reduced cytotoxicity compared to established cationic polymer vector – polyethylenimine with a weight average molecular weight (Mw) of 25,000 Dalton (PEI25K). The carrier PHPA-PEI1800-FA was synthesized in a two-step procedure. PHPA-PEI1800 was prepared by grafting polyethylenimine with a Mw of 1800 Dalton (PEI1800) onto the α,β-poly(N-3-hydroxypropyl)-D,L-aspartamide (PHPA) backbone. PHPA-PEI1800-FA was obtained by chemically conjugating folic acid onto PHPA-PEI1800. The grafting degree of PEI1800 was 3.9±0.2% in relation to the CH groups of PHPA and the molar ratio of folic acid conjugated to PEI1800 (χFA) was 1.8±0.1 as calculated by NMR spectroscopy. The copolymers were biodegradable and exhibited lower cytotoxicity than PEI25K. Compared to PHPA-PEI1800, PHPA-PEI1800-FA led to a significantly higher transfection efficiency in human MSCs, which could be attributed to the mediation of folate receptor during the transfection process as confirmed by folic acid competition assay. Both marker gene (GFP) and therapeutic gene (VEGF) were delivered into human MSCs from multi-donors using PHPA-PEI1800-FA. The percentage of GFP+ MSCs showed an average value of 2.85±1.60% but a large variation for different samples. The VEGF expression level of the PHPA-PEI1800-FA transfected cells was significantly higher than that of either untransfected or naked DNA transfected cells. Conclusively, PHPA-PEI1800-FA is a suitable vector to deliver genes into human MSCs through the interaction with folate receptor. %0 journal article %@ 1381-6128 %A Wang, W.,Deng, Z.,Xu, X.,Li, Z.,Jung, F.,Ma, N.,Lendlein, A. %D 2017 %J Current Pharmaceutical Design %N 26 %P 3814-3832 %R doi:10.2174/1381612823666170622110654 %T Functional Nanoparticles and their Interactions with Mesenchymal Stem Cells %U https://doi.org/10.2174/1381612823666170622110654 26 %X Mesenchymal stem cells (MSCs) have become one of the most important cell sources for regenerative medicine. However, some mechanisms of MSC-based therapy are still not fully understood. The clinical outcome may be restricted by some MSC-related obstacles such as the low survival rate, differentiation into undesired lineages and malignant transformation. In recent years, with the emergence of nanotechnology, various types of multifunctional nanoparticles (NPs) have been designed, prepared and explored for bio-related applications. There is high potential of NPs in biomedical applications, attributed to the high capacity of cellular internalization in MSCs and their multiple functionalities. They can be used either as labeling agent to track MSCs for mechanism study or as gene/drug delivery carriers to regulate the cellular behavior and functions of MSCs. However, the application of NPs may be accompanied by some undesirable effects, as some NPs can induce cell death, inhibit cell proliferation or influence the differentiation of MSCs. Aiming to provide a comprehensive understanding of the interaction between NPs and MSCs, recent progress in the design and preparation of multifunctional NPs is summarized in this review, mechanisms of cellular internalization of the NPs are discussed, the main applications of multifunctional NPs in MSCs are highlighted and overview about cellular response of MSCs to different NPs is given. Future studies aiming on design and development of NPs with multifunctionality may open a new field of applying nanotechnology in stem cell-based therapy. %0 conference poster %@ %A Mrowietz, C.,Franke, R.,Pindur, G.,Wolf, U.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Reference range and variability of Laser-Doppler-Fluxmetry %U %X %0 conference poster %@ %A Assuncao, M.,Walter, M.,Bäckemo Johansson, J.,Topczewska, P.,Krüger-Genge, A.,Braune, S.,Roch, T.,Blocki, A.,Behl, M.,Jannasch, A.,Matschke, K.,Klopfleisch, R.,Jung, F.,Lendlein, A. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Characterization of PCL-BA copolymer networks for application as vascular patch %U %X %0 conference lecture %@ %A Krüger-Genge, A.,Hauser, S.,Neffe, A.,Pietzsch, J.,Lendlein, A.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Endothelialisation of gelatin- based hydrogels with different elasticity and degradation time %U %X %0 conference lecture %@ %A Braune, S.,Bäckemo Johansson, J.,Reinthaler, M.,Landmesser, U.,Lendlein, A.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Effects of anticoagulants on blood cell interactions with polymers %U %X %0 conference lecture (invited) %@ %A Braune, S.,Sperling, C.,Maitz, M.,Steinseifer, U.,Clauser, J.,Hiebl, B.,Krajewski, S.,Wendel, H.,Jung, F. %D 2017 %J Conference on Blood-Biomaterial Interactions - Bloodsurf 2017 %N %P %T Thrombogenicity testing of polymers: round-robin study to assess inter-center variability %U %X %0 conference lecture %@ %A Lamby, P.,Prantl, L.,Krüger-Genge, A.,Franke, R.,Jung, E.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Influence of Ultrasound Microbubble on the kidney oxygen tension %U %X %0 conference lecture %@ %A Li, Z.,Xu, X.,Wang, W.,Kratz, K.,Sun, X.,Zou, J.,Deng, Z.,Jung, F.,Gossen, M.,Ma, N.,Lendlein, A. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Preconditioning with topographic microstructure of materials promotes the migration capacity of adipose derived mesenchymal stem cells %U %X Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic,potential. Various approaches are employed to effectively influence the migration capacity of MSCs.,Here, topographic microstructures in three different roughness levels (R0: Rq = 0.12 ± 0.04μm, R1: Rq =,3.52 ± 0.26μm, R2: Rq = 16.04 ± 1.24μm) were created on polystyrene (PS) culture vessel surfaces as a,feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells,migrating after preconditioning, we demonstrated that mobilization velocity of human adipose derived,mesenchymal stem cells (hADSCs) could be promoted by preconditioning with the appropriate microtopography.,After 7 days preconditioning, migration velocities of the surfaces preconditioned cells were,0.47 ± 0.02 μm/min (R0), 0.54 ± 0.02 μm/min (R1) and 0.45 ± 0.02 μm/min (R2) respectively. Moreover,,different activation levels of focal adhesion kinase (FAK), RhoA and Rac-1 of hADSCs from the three,surfaces were observed. After 7 days preconditioning, the microstructure surface in R1 roughness,significantly increased the phosphorylated FAK level (pFAK/total protein: R1, 1.51 ± 0.11 unit/μg),compared with the other two surfaces (pFAK/total protein: R0, 1.15 ± 0.03 unit/μg; R2, 1.25 ± 0.04,unit/μg). Meanwhile, the RhoA activity was increased and Rac-1 activity was decreased by,microstructure surface in R1 roughness. Our data indicated that the microstructure preconditioning,promoted cell migration ability via modulating the activation of FAK and Rho family. These findings,underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via,transplantation of topographic microstructure preconditioned stem cells. %0 conference poster %@ %A Hiebl, B.,Peters, S.,Gemeinhardt, O.,Niehues, S.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Impact of serum on lactate dehydrogenase (LDH) rlease determination in vitro %U %X According to the DIN EN ISO 10993-5 which contains recommendations on the biological,evaluation of medical devices cellular release of enzymes is a sufficient parameter to,determine cytotoxicity. Generally, there are two possibilities for cells in culture to react,towards cytotoxic substrates. They can stop growing or dividing, or they can die through,necrosis or apoptosis. Necrosis is accompanied by mitochondrial swelling and increased,plasma membrane permeability, while apoptosis involves an articulated breakdown of the cell,into membrane-bound apoptotic bodies. In this way necrosis and apoptosis result in a,compromised or damaged cell membrane, and lactate dehydrogenase (LDH), a soluble,enzyme of the cytoplasm, becomes released into the extracellular space. Since this only,happens when cell membrane integrity is compromised, the content of this enzyme in the,supernatants from cells can be used as an indicator of damaged cell membrane integrity and,serve as a general means to assess cell viability by measuring plasma membrane permeability.,However, cell culture media, which are used to maintain and to support cell growth,commonly need serum supplementation, and the serum content varies depending on the,cellular needs. Additionally, sera already contain various LDH amounts, which may increase,background absorbance in LDH release assays. For this reasons we tested the effect of,different serum loads (inactivated fetal bovine serum [FBS]; 1-10 vol%) on the results of a,commercially available LDH release assay (Cytotoxicity detection Kit, Roche) using 3T3,cells. An FBS concentration of 1 vol% was found to provide the best compromise between,cell growth support and variability of the results. Test with primary cells will be performed in,the future to confirm these results. %0 conference poster %@ %A Krüger-Genge, A.,Hiebl, B.,Schunck, W.,Müller, D.,Blaschke, F.,Franke, R.,Lendlein, A.,Jung, F. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Effects of tacrolimus or sirolimus on the adhesion of vascular wall cells: controlled in-vitro camparison study %U %X %0 conference lecture %@ %A Blocki, A.,Löper, F.,Chirico, N.,Neffe, A.,Jung, F.,Stamm, C.,Lendlein, A. %D 2017 %J 36. Jahrestagung der Deutschen Gesellschaft für Klinische Mikrozirkulation und Hämorheologie %N %P %T Engineering of cell-laden gelatin-based microcapsules for cell delivery and immobilization in cell-based regenerative therapies %U %X %0 conference poster %@ %A Blocki, A.,Loewenberg, C.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J Advanced Functional Polymers for Medicine, AFPM 2016 %N %P %T Mechanobiological response of encapsulated cells to a gelatin matrix with varied crosslinking density %U %X %0 editorial %@ 1386-0291 %A Jung, F.,Rampling, M. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 251-254 %R doi:10.3233/CH-168108 %T Editorial: Role of blood viscosity in the microcirculation %U https://doi.org/10.3233/CH-168108 3 %X No abstract %0 conference lecture %@ %A Kaessmeyer, S.,Sehl, J.,Khiao In, M.,Hiebl, B.,Merle, R.,Jung, F.,Franke, R.P.,Plendl, J. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Organotypic soft-tissue co-cultures: Morphological changes in microvascular endothelial tubes after incubation with iodinated contrast media %U %X %0 journal article %@ 1386-0291 %A Kaessmeyer, S.,Sehl, J.,Khiao In, M.,Hiebl, B.,Merle, R.,Jung, F.,Franke, R.P.,Plendl, J. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 391-402 %R doi:10.3233/CH-168119 %T Organotypic soft-tissue co-cultures: Morphological changes in microvascular endothelial tubes after incubation with iodinated contrast media %U https://doi.org/10.3233/CH-168119 3 %X INTRODUCTION: Clinical complications like thrombosis or anaphylaxis have been described to go along with the intra-venous or intra-arterial injection of iodinated contrast media (CM). It has been suggested that the administration of CM affects rheological parameters and thereby causes reduced blood velocity in microvessels. In vitro studies revealed significant buckling of endothelial cells after exposure to CM reducing the lumen of vessels. The aim of this study was to test the influence of CM on three-dimensional microvascular tubules with open lumina within an organotypic soft-tissue co-culture assay in vitro. This model, which is based on the co-culture of endothelial cells and fibroblasts, allows the analysis and quantitation of different parameters of microvascular endothelial capillary structures.,MATERIAL AND METHODS: Human dermal fibroblasts and human dermal microvascular endothelial cells were co-cultured for 10 days. Fibroblasts were adapted to the endothelial cell medium before co-culture and allowed to proliferate as well as produce extracellular matrix. The co-cultures were exposed to three different CM, i.e., Iomeprol (Imeron 400MCT), Iodixanol (Visipaque 320) or Iohexol (Accupaque 350) for 1.5 minutes or 5.0 minutes, respectively. For this, a mixture of CM and cell culture medium in a ratio of 30% CM by volume was prepared. After fixation in methanol/acetone, the endothelial cells were immunolabeled with the endothelial marker anti-CD31 and the tubular structures were assessed morphometrically.,RESULTS: In the organotypic soft-tissue co-cultures with fibroblasts, the endothelial cells developed three-dimensional capillary-like structures which expanded via sprouting branches. After incubation with the different CM, the numbers of endothelial tubes (p = 0.001) and their lengths (p = 0.003) were significantly lower after the 5 minutes incubation time, when compared to the 1.5 minutes incubation time. The tubular diameters were significantly reduced after 5 minutes (p < 0.001), when compared to the 1.5 minutes incubation duration. Interestingly, Iomeprol and Iodixanol induced an elongation of the tubular branches during incubation duration of 1.5 minutes (p = 0.015). However, after 5 minutes incubation, the tubular branches were drastically shorter in the presence of Iomeprol and Iodixanol than the tubular branches of the control (p = 0.007). %0 conference lecture %@ %A Tzoneva, R.,Uzunova, V.,Apostolova, S.,Krueger-Genge, A.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Angiogenic potential of endothelial and tumor cells seeded on gelatin–based hydrogels in response to electrical stimulations %U %X %0 journal article %@ 1386-0291 %A Tzoneva, R.,Uzunova, V.,Apostolova, S.,Krueger-Genge, A.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 941-949 %R doi:10.3233/CH-168040 %T Angiogenic potential of endothelial and tumor cells seeded on gelatin–based hydrogels in response to electrical stimulations %U https://doi.org/10.3233/CH-168040 4 %X Angiogenesis is one of the key processes during development, wound healing and tumor formation. Prerequisite for its existence is the presence of endogenous electrical fields (EFs) generated by active ion transport across polarized epithelia and endothelia, and appearance of the transcellular potentials. During angiogenesis cellular factor as endothelial growth factor (VEGF), synthesis of adhesive proteins and membrane metalloproteinases (MMPs) govern the angiogenic response to different external stimuli as biomaterials interactions and/or exogenous EF. Gelatin-based hydrogels with elasticities comparable to human tissues have shown to influence cell behavior as well as cell attachment, protein synthesis, VEGF and MMP’s production after the application of EF. Gelatin-based matrices with 3 (G10_LNCO3), 5 (G10_LNCO5), and 8 (G10_LNCO8) fold excess of isocyanate groups per mol of amine groups present in gelatin were used. Human umbilical endothelial cells (HUVEC) (Lonza Basel, Switzerland) and highly invasive breast cancer MDA-MB-231 cells (ATCC®HTB-26TM) were used. For an estimation of the amount of VEGF released from cells a commercially available VEGF ELISA (Thermo Fisher Scientific, Germany) kit was used. Fibronectin (FN) enzyme immunoassay (EIA) was used to analyze the secreted amount of FN by cells seeded on the materials. Secreted MMPs were analyzed by zymography. Gelatin-based hydrogels attracted HUVEC adhesion and diminished the adhesion of MDA-MB-231 cells. The applied direct current (DC) EF induced an almost 5–fold increase in VEGF production by HUVEC seeded on gelatin-based hydrogels, while in contrast, the applied EF decreased the production of VEGF by cancer cells. FN synthesis was elevated in HUVEC cells seeded on gelatin-based materials in comparison to FN synthesis by cancer cells. HUVEC seeded on gelatin hydrogels showed an expression mainly of MMP-2. The application of EF increased the production of MMP-2 in HUVEC seeded on gelatin materials. In contrast, for MDA-MB-231 the production of MMPs on gelatin materials was lower compared to control materials. With the application of EF the levels of MMP-9 decreased but MMP-2 expression raised significantly for gelatin materials. Overall, the results showed that studied gelatin materials suppressed attachment of cancerous cells, as well as suppressed their angiogenic potential revealed by decreased VEGF and MMP production. Thus, this study approved gelatin-based hydrogels with proper elasticity characteristics and different degradation behavior as useful matrices for use in vascular tissue regeneration or in restriction of tumor growth after tumor resection. %0 conference lecture %@ %A Gerk, U.,Mrowietz, C.,Sternitzky, R.,Franke, R.P.,Spitzer, S.G.,Jung, F. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Effect of Ioxaglate on the cutaneous microcirculation in patients with coronary artery disease: Randomized, double blind, placebo-controlled study %U %X %0 journal article %@ 1386-0291 %A Gerk, U.,Mrowietz, C.,Sternitzky, R.,Franke, R.P.,Spitzer, S.G.,Jung, F. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 297-304 %R doi:10.3233/CH-168101 %T Effect of Ioxaglate on the cutaneous microcirculation in patients with coronary artery disease: Randomized, double blind, placebo-controlled study %U https://doi.org/10.3233/CH-168101 3 %X Radiographic contrast media (RCM) can initiate microcirculatory disorders. This study was performed to investigate effects of Ioxaglate on the cutaneous microcirculation. The investigation was carried out as prospective randomized double-blind comparison in parallel-group design on two groups of n = 10 patients each who had to undergo a diagnostic coronary angiography.,The confirmatory parameter of the study was mean erythrocyte capillary velocity [vRBC in mm/sec]. VRBC in the ipsilateral nail-fold capillaries was recorded continuously for 3 min before and 6 min after injection of RCM or isotonic saline solution in the A. axillaris respectively, and was evaluated off-line.,VRBC in nailfold capillaries was found to be decreased by Ioxaglate by 34% 150 seconds after injection, while isotonic NaCl solution immediately induced a slight increase of 14%. %0 journal article %@ 1556-9845 %A Wilbring, M.,Jung, F.,Weber, C.,Matschke, K.,Knaut, M. %D 2016 %J Innovations %N 1 %P 24-30 %R doi:10.1097/IMI.0000000000000231 %T Reduced Incidence of Thromboembolic Events After Surgical Closure of Left Atrial Appendage in Patients With Atrial Fibrillation %U https://doi.org/10.1097/IMI.0000000000000231 1 %X Objective: Most of the detected thrombi in patients with atrial fibrillation (AF) can be found in the left atrial appendage (LAA). Interventional LAA closure recently proved to be noninferior to warfarin therapy. Whether these results can be fully translated into surgical LAA closure remains unclear. Corresponding data are still lacking. The present observational study evaluated the impact of surgical LAA closure in patients with AF undergoing cardiac surgery on postoperative thromboembolic events.,Methods: A prospective registry enrolled 398 patients with permanent AF undergoing cardiac surgery. Concomitant procedures were isolated surgical ablation (group I, n = 71), isolated LAA closure (group II, n = 44), and combined surgical ablation and LAA closure (group III, n = 196). The control group consisted of 87 patients without concomitant surgical ablation or LAA closure. One-year follow-up was completed in all patients. End points were thromboembolic events and death from any cause.,Results: Clinical baseline characteristics were comparable among the groups. General hospital mortality was 5.5% and likewise differed not significantly. Postoperatively, mean (SD) CHAD2S2-VASc score of 3.5 (1.3) differed not significantly among the groups, indicating comparable thromboembolic risk. Follow-up referred to all hospital survivors (n = 376). Herein, overall incidence of thromboembolic events was 9.8% (n = 37), with an associated mortality of 41.0%. Patients with LAA closure alone or in combination with surgical ablation had a significantly reduced incidence of thromboembolic events (6.6% vs 20.5%, P < 0.01) and consecutively improved survival after 1 year of follow-up (7.0% vs 17.1%, P < 0.01).,Conclusions: Left atrial appendage closure alone or in combination with surgical ablation was associated with a significantly reduced rate of thromboembolic events and consecutively improved survival after 1 year of follow-up. %0 editorial %@ 1386-0291 %A Jung, C.,Jung, F.,Kelm, M. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 169-172 %R doi:10.3233/CH-1663301 %T Editorial: The microcirculation in hypoxia: The center of the battlefield for oxygen %U https://doi.org/10.3233/CH-1663301 3 %X In the past years the microcirculation has gained increasing attention not only by basic scientists, but also by,clinicians and translational researchers. In the clinical scenario, it has been convincingly described that the microcirculation,is a key predictor of outcome and of central pathophysiological relevance.Avast body of evidence demonstrates the central role of the smallest vessels in inflammation, hyperviscosity, cell-cell-interaction, endothelial function, tissue edema, hemodynamic and blood flow regulation and its important role in the interaction with soluble factors. A central feature of different diseases,and a strong regulator of different changes is hypoxia, the lack of oxygen. Also the microcirculation is on one hand a central component responding with dynamic changes to hypoxia but also the central place where hypoxia mediates its,unfavorable effects. These changes and associated interactions are the topic of this special thematic issue “Hypoxia” in Clinical Hemorheology and Microcirculation and it seems logical that important and relevant findings are presented. %0 journal article %@ 1386-0291 %A Braune, S.,Basu, S.,Kratz, K.,Johansson, J.B.,Reinthaler, M.,Lendlein, A.,Jung, F. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 345-353 %R doi:10.3233/CH-168114 %T Strategy for the hemocompatibility testing of microparticles %U https://doi.org/10.3233/CH-168114 3 %X Polymer-based microparticles are applied as non-thrombogenic or thrombogenic materials in a wide variety of intra- or extra-corporeal medical devices. As demanded by the regulatory agencies, the hemocompatibility of these blood contacting biomaterials has to be evaluated in vitro to ensure that the particle systems appropriately fulfill the envisioned function without causing undesired events such as thrombosis or inflammation. Currently described in vitro assays for hemocompatibility testing of particles comprise tests with different single cell types (e.g. erythrocytes or leukocytes), varying concentrations/dilutions of the used blood cells or whole blood, which are not standardized.,Here, we report about an in vitro dynamic test system for studying the hemocompatibility of polymeric microparticles utilizing fresh human whole blood from apparently healthy subjects, collected and processed under standardized conditions. Spherical poly(ether imide) microparticles with an average diameter of 140±30 μm were utilized as model systems. Reported as candidate materials for the removal of uremic toxins, these microparticles are anticipated to facilitate optimal flow conditions in a dialyzer with minimal backflow and blood cell damage. Pristine (PEI) and potassium hydroxide (PEI-KOH) functionalized microparticles exhibited similarly nanoporous surfaces (PEI: ØExternal pore = 90±60 nm; PEI-KOH ØExternal pore = 150±130 nm) but varying water wettabilities (PEI: θadv = 112±10° PEI-KOH θadv = 60±2°). The nanoporosity of the microparticle surfaces allows the exchange of toxic solutes from blood towards the interconnective pores in the particle core, while an immigration of the substantially larger blood cells is inhibited.,Sterilized PEI microparticles were incorporated –air-free –in a syringe-based test system and exposed to whole blood for 60 minutes under gentle agitation. Thereafter, thrombi formation on the particles surfaces were analyzed microscopically. In the collected whole blood the non-adherent/circulating single blood cells were quantified via a differentiated complete blood cell count and the activation of platelets (P-Selectin expression, secretion and release), platelet function (PFA100 closure time) as well as thrombin formation (thrombin-antithrombin-complex) was analyzed. Free hemoglobin (HGB) levels were quantified as a measure of hemolysis.,Microscopic evaluation revealed thrombi formation and particle aggregates for all tested microparticles. Reduction of circulating blood cells differed significantly between the particle types. Particularly, platelet and monocyte counts decreased up to 50% compared to the control (syringe filled with whole blood but without microparticles). In accordance, platelet activation, thrombin levels and degrees of hemolysis were clearly elevated in the particle loaded test systems and allowed a differentiation between the particle types. Increased PFA100 closure times (as activating agent a combination of collagen/ADP was used) indicated a similarly reduced ability of platelets to adhere and form stable aggregates independent from the particle type tested. This observation is most probably a consequence of the strong thrombus formation in the test system, which is associated with a reduction of the circulating blood cells.,The reported in vitro dynamic whole blood test system allowed the sensitive analysis of the hemocompatibility of polymer-based microparticles and was successfully validated for porous PEI microparticles with different water wettabilities. Beyond the qualitative and quantitative analysis of cell-material interactions, the test also allowed the functional evaluation of platelets in whole blood. %0 conference lecture %@ %A Krueger-Genge, A.,Schulz, C.,Jung, F.,Fuhrmann, R.,Lendlein, A.,Franke, R.-P. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Shear resistance of endothelial cells in a pathological environment %U %X %0 journal article %@ 1552-4973 %A Braune, S.,Gross, M.,Walter, M.,Zhou, S.,Dietze, S.,Rutschow, S.,Lendlein, A.,Tschoepe, C.,Jung, F. %D 2016 %J Journal of Biomedical Materials Research B %N 1 %P 210-217 %R doi:10.1002/jbm.b.33366 %T Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials %U https://doi.org/10.1002/jbm.b.33366 1 %X On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet—indicating the spreading and activation of the platelets—was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials. %0 journal article %@ 1559-4106 %A Jung, F.,Braune, S. %D 2016 %J Biointerphases %N 2 %P 029601 %R doi:10.1116/1.4938557 %T Thrombogenicity and hemocompatibility of biomaterials %U https://doi.org/10.1116/1.4938557 2 %X No abstract %0 journal article %@ 1386-0291 %A Braune, S.,Froehlich, G.M.,Lendlein, A.,Jung, F. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 681-688 %R doi:10.3233/CH-152028 %T Effect of temperature on platelet adherence %U https://doi.org/10.3233/CH-152028 4 %X BACKGROUND:,Thrombogenicity is one of the main parameters tested in vitro to evaluate the hemocompatibility of artificial surfaces. While the influence of the temperature on platelet aggregation has been addressed by several studies, the temperature influence on the adherence of platelets to body foreign surfaces as an important aspect of biomedical device handling has not yet been explored. Therefore, we analyzed the influence of two typically applied incubation-temperatures (22°C and 37°C) on the adhesion of platelets to biomaterials.,MATERIAL AND METHODS:,Thrombogenicity of three different polymers - medical grade poly(dimethyl siloxane) (PDMS), polytetrafluoroethylene (PTFE) and polyethylene terephthalate (PET) - were studied in an in vitro static test. Platelet adhesion was studied with stringently characterized blood from apparently healthy subjects. Collection of whole blood and preparation of platelet rich plasma (PRP) was carried out at room temperature (22°C). PRP was incubated with the polymers either at 22°C or 37°C. Surface adherent platelets were fixed, fluorescently labelled and assessed by an image-based approach.,RESULTS AND DISCUSSION:,Differences in the density of adherent platelets after incubation at 22°C and 37°C occurred on PDMS and PET. Similar levels of adherent platelets were observed on the very thrombogenic PTFE. The covered surface areas per single platelet were analyzed to measure the state of platelet activation and revealed no differences between the two incubation temperatures for any of the analyzed polymers. Irrespective of the observed differences between the low and medium thrombogenic PDMS and PET and the higher variability at 22°C, the thrombogenicity of the three investigated polymers was evaluated being comparable at both incubation temperatures. %0 journal article %@ 0028-0836 %A Ljungqvist, F.C.,Krusic, P.J.,Sundqvist, H.S.,Zorita, E.,Brattstroem, G.,Frank, D. %D 2016 %J Nature %N 7597 %P 94-98 %R doi:10.1038/nature17418 %T Northern Hemisphere hydroclimate variability over the past twelve centuries %U https://doi.org/10.1038/nature17418 7597 %X Accurate modelling and prediction of the local to continental-scale hydroclimate response to global warming is essential given the strong impact of hydroclimate on ecosystem functioning, crop yields, water resources, and economic security1, 2, 3, 4. However, uncertainty in hydroclimate projections remains large5, 6, 7, in part due to the short length of instrumental measurements available with which to assess climate models. Here we present a spatial reconstruction of hydroclimate variability over the past twelve centuries across the Northern Hemisphere derived from a network of 196 at least millennium-long proxy records. We use this reconstruction to place recent hydrological changes8, 9 and future precipitation scenarios7, 10, 11 in a long-term context of spatially resolved and temporally persistent hydroclimate patterns. We find a larger percentage of land area with relatively wetter conditions in the ninth to eleventh and the twentieth centuries, whereas drier conditions are more widespread between the twelfth and nineteenth centuries. Our reconstruction reveals that prominent seesaw patterns of alternating moisture regimes observed in instrumental data12, 13, 14 across the Mediterranean, western USA, and China have operated consistently over the past twelve centuries. Using an updated compilation of 128 temperature proxy records15, we assess the relationship between the reconstructed centennial-scale Northern Hemisphere hydroclimate and temperature variability. Even though dry and wet conditions occurred over extensive areas under both warm and cold climate regimes, a statistically significant co-variability of hydroclimate and temperature is evident for particular regions. We compare the reconstructed hydroclimate anomalies with coupled atmosphere–ocean general circulation model simulations and find reasonable agreement during pre-industrial times. However, the intensification of the twentieth-century-mean hydroclimate anomalies in the simulations, as compared to previous centuries, is not supported by our new multi-proxy reconstruction. This finding suggests that much work remains before we can model hydroclimate variability accurately, and highlights the importance of using palaeoclimate data to place recent and predicted hydroclimate changes in a millennium-long context. %0 conference lecture %@ %A Schulz, C.,Vukicevic, R.,Krueger-Genge, A.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Cell layer formation and shear-resistance of human endothelial cells on gelatin-based hydrogels with tailorable elasticity %U %X %0 journal article %@ 2352-3697 %A Hiebl, B.,Scharnagl, N.,Kaessmeyer, S.,Gemeinhardt, O.,Gemeinhardt, I.,Niehues, S.M.,Peters, S.,Jung, F. %D 2016 %J Journal of Cellular Biotechnology %N 2 %P 145-150 %R doi:10.3233/JCB-15014 %T Influence of the blood exposure time in dynamic hemocompatibility testing on coagulation and C5a activation %U https://doi.org/10.3233/JCB-15014 2 %X Within the hemocompatibility testing portfolio of medical devices a range of dynamic models were established in recent years. In contrast to the static hemocompatibility testing method the dynamic models allow considering the impact of hemorheological and hemodynamic blood characteristics on the hemocompatibility of medical devices. Unfortunately the EN DIN ISO 10993-4 for the biological evaluation of medical devices for interaction with blood gives no hints towards the period of time during which the medical devices should be exposed to the blood in these tests. To examine whether different exposure times impact the comparability of hemocompatibility test results low density polyethylene (LD-PE) tubes and nitinol stents were tested exemplarily in a closed loop model for changes of the fibrinogen content, the prothrombin time, the thrombin time, and the C5a activity after 30 and 90 min exposure to the blood. Low density polyethylene was used as negative control because it is one of the European reference materials for hemocompatibility testing. After 90 min blood exposure to the LD-PE tubing and the nitinol stents the prothrombin time was significantly longer and the fibrinogen content significantly lower (p < 0.05) than after 30 min. In contrast the thrombin time and the C5a were comparable after 30 and 90 min blood exposure time. These results might recommend to an initial 30 min exposure time, which is followed by a 90 min exposure time in cases of unclear results. %0 journal article %@ 1386-0291 %A Krueger-Genge, A.,Jung, F.,Fuhrmann, R.,Franke, R.-P. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 383-389 %R doi:10.3233/CH-168111 %T Shear resistance of endothelial cells in a pathological environment %U https://doi.org/10.3233/CH-168111 3 %X BACKGROUND: Endothelial cells (EC) in vivo are strongly influenced by changes of the milieu exterieur. Under pathological conditions EC can become activated e.g. in hypoxic areas or during sepsis. In general, the endothelialization of implant materials is evaluated in vitro under physiological conditions. Though, in patients who receive implant materials pathological conditions are often present. An open question is therefore, how ECs seeded on a body foreign substrate behave in a pathologic microenvironment. In this in vitro study a microenvironment was created mimicking the conditions present in septic patients. To simulate this situation in vitro, serum of patients with septic shock was added to the culture medium of EC cultured on glass. The samples were sheared in a cone-plate rheometer (shear rate of 6 dyn/cm2) with subsequent analysis of the morphology, the microfilament organization and the shear resistance and compared to control cultures of EC without shock serum supplementation. Aim of the study was to investigate whether this in vitro model provides information about the functionality of an EC monolayer on a body foreign surface under pathological conditions.,RESULTS: Septic conditions induced severe changes of the morphology of the adherent cells: there was a strong induction of stress fibers. In addition, lots of cells or cell groups were detached visible as denuded areas in the EC monolayer. After shear stress exposure only 28.7% of EC seeded in cell medium supplemented with serum of septic patients remained adherent (control cells: 96.8%).,CONCLUSION: The study demonstrates that the microenvironment is of extreme importance for the behavior of EC and that in vivo pathologies can be simulated in vitro. This opens the possibility to evaluate new implant materials under physiological but more important also under certain pathological conditions - simulating the implant size and the disease of the host. %0 conference lecture %@ %A Braune, S.,Basu, S.,Kratz, K.,Johansson, J.B.,Reinthaler, M.,Lendlein, A.,Jung, F. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Strategy for the hemocompatibility testing of microparticles %U %X %0 conference lecture %@ %A Mandlik, V.,Kehrer, A.,Jiga, L.,Hoinoiu, B.,Ionac, M.,Jung, F.,Staudenmaier, R.,Prantl, L. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Prefabrication and free transfer of a Tissue Engineered Composite Flap – An experimental model in the rat %U %X %0 journal article %@ 1386-0291 %A Mandlik, V.,Kehrer, A.,Jiga, L.,Hoinoiu, B.,Ionac, M.,Jung, F.,Staudenmaier, R.,Prantl, L. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 319-331 %R doi:10.3233/C-168120 %T Prefabrication and free transfer of a Tissue Engineered Composite Flap – An experimental model in the rat %U https://doi.org/10.3233/C-168120 3 %X BACKGROUND: The technique of flap-prefabrication has been successfully established in tissue engineering: missing intrinsic vascularisation of engineered tissue can be generated in vivo by microsurgical vesselloop construction. It is possible to move engineered tissue into a defect with microsurgery. In the literature, the combination of engineered tissue covered with skin is not widely reported.,OBJECTIVE: Aim of this study was to establish a model to investigate scaffold prefabrication with full thickness skin graft coverage with subsequent free tissue transfer.,METHODS: 8 Wistar rats were operated in 2 separate steps: 1) after creating an arteriovenous loop with the femoral vessels, a porous scaffold was placed on the loop and covered with an inguinally based skin flap. A control was implanted without loop into the contralateral groin. 2) 6 weeks later the prefabricated composite flaps were microsurgically transferred to the cervical region. Skin-island monitoring was performed with Laser Doppler-scanner after the transfer.,RESULTS: Continuous loss of the skin islands was observed within 72 hours. Complications included wound-dehiscence, thrombosis and death from anaesthesia; in spite of consistent loop viability.,CONCLUSION: Evaluation showed that modifications are necessary to maintain the skin-island cove. %0 conference poster %@ %A Blocki, A.,Loewenberg, C.,Jiang, Y.,Kratz, K.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2016 %J RegMed Forum - 10 Jahre BCRT %N %P %T Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties %U %X %0 conference lecture %@ %A Krueger-Genge, A.,Jung, F.,Fuhrmann, R.,Franke, R.-P. %D 2016 %J 18th European Conference for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Effects of different components of the extracellular matrix on endothelialization %U %X %0 conference lecture %@ %A Lamby, P.,Jung, F.,Falter, J.,Mrowietz, C.,Graf, S.,Schellenberg, L.,Platz Batista da Silva, N.,Prantl, L.,Franke, R.-P.,Jung, E.M. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Effect of radiographic contrast media on renal perfusion – First results %U %X %0 journal article %@ 1386-0291 %A Lamby, P.,Jung, F.,Falter, J.,Mrowietz, C.,Graf, S.,Schellenberg, L.,Platz Batista da Silva, N.,Prantl, L.,Franke, R.-P.,Jung, E.M. %D 2016 %J Clinical Hemorheology and Microcirculation %N 3 %P 287-295 %R doi:10.3233/CH-168110 %T Effect of radiographic contrast media on renal perfusion – First results %U https://doi.org/10.3233/CH-168110 3 %X BACKGROUND: Intra-arterial administration of radiographic contrast media (CM) is discussed to impair renal perfusion. The pathogenesis of contrast-induced Nephropathy (CIN) is still not clarified.,OBJECTIVE: This trial was performed to prove the effects of two CM with different molecular structure on renal perfusion.,METHODS: A prospective, randomized study on 16 pigs was designed to compare the outcome after application of a low-osmolar iodinated CM (770 mOsm/kg H2O – Group1) and an iso-osmolar iodinated CM (290 mOsm/kg H2o – Group2).,Color Coded Doppler Sonography (LOGIQ E9, GE, Milwaukee, USA) was applied for measuring the Renal Resistive Index (RRI) before and after the first, fifth, and tenth bolus of CM. Statistics was performed using analysis of variance for repeated measurements with the Factor “CM”.,RESULTS: All flow spectra were documented free of artifacts and Peak Systolic Velocity (PSV), Enddiastolic Velocity (EDV) and RRI respectively could be calculated. Mean PSV in Group 1 led to a decrease while in Group 2 PSV showed a significant increase after CM (p = 0,042). The course of the mean EDV in both groups deferred accordingly (p = 0,033). Mean RRI over time significantly deferred in both groups (p = 0,001). It showed a biphasic course in Group 2 and a decrease over time in Group 2.,CONCLUSION: While iso-osmolar CM induced an increase of PSV and EDV together with a decrease of RRI, low-osmolar CM could not show this effect or rather led to the opposite. %0 editorial %@ 1386-0291 %A Gori, T.,Jung, F. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 507-508 %R doi:10.3233/CH-168005 %T Editorial %U https://doi.org/10.3233/CH-168005 4 %X No abstract %0 conference lecture %@ %A Schulz, C.,Vukicevic, R.,Krueger-Genge, A.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J 18th European Conference for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Monolayer formation and shear-resistance of human umbilical vein endothelial cells on gelatin-based hydrogels with tailorable elsticity and degradability %U %X %0 journal article %@ 1559-4106 %A Reinthaler, M.,Braune, S.,Lendlein, A.,Landmesser, U.,Jung, F. %D 2016 %J Biointerphases %N 2 %P 029702 %R doi:10.1116/1.4953246 %T Platelets and coronary artery disease: Interactions with the blood vessel wall and cardiovascular devices %U https://doi.org/10.1116/1.4953246 2 %X In view of the rare presence of studies concerning platelet function as risk factor in atherosclerotic patients, processes underlying thromboembolic events are reviewed in this paper. The morphology and the structural organization—membrane receptors, the open canalicular and dense tubular systems, the cytoskeleton, mitochondria, granules, lysosomes, and peroxisomes—of platelets are described. Platelet function under physiological conditions in atherosclerosis and after implantation of cardiovascular devices is summarized. %0 journal article %@ 1748-9326 %A Luterbacher, J.,Werner, J.P.,Smerdon, J.E.,Fernandez-Donado, L.,Gonzalez-Rouco, F.J.,Barriopedro, D.,Ljungqvist, F.C.,Buentgen, U.,Zorita, E.,Wagner, S.,Esper, J.,McCarroll, D.,Toreti, A.,Frank, D.,Jungclaus, J.H.,Barriendos, M.,Bertolin, C.,Bothe, O.,Brazdil, R.,Camuffo, D.,Cobrovolny, P.,Gagen, M.,Garcia-Bustamante, E.,Ge, Q.,Gomez-Navarro, J.J.,Guiot, J.,Hao, Z.,Hegerl, G.C.,Holmgren, K.Klimenko, V.V.,Martin-Chivelet, J.,Pfister, C.,Roberts, N.,Schindler, A.,Schurer, A.,Solomina, O.,Gunten, L.v.,Wahl, E.,Wanner, H.,Wetter, O.,Xoplaki, E.,Yuan, N.,Zanchettin, D.,Zhang, H.,Zerefos, C. %D 2016 %J Environmental Research Letters %N 2 %P 024001 %R doi:10.1088/1748-9326/11/2/024001 %T European summer temperatures since Roman times %U https://doi.org/10.1088/1748-9326/11/2/024001 2 %X The spatial context is critical when assessing present-day climate anomalies, attributing them to potential forcings and making statements regarding their frequency and severity in a long-term perspective. Recent international initiatives have expanded the number of high-quality proxy-records and developed new statistical reconstruction methods. These advances allow more rigorous regional past temperature reconstructions and, in turn, the possibility of evaluating climate models on policy-relevant, spatio-temporal scales. Here we provide a new proxy-based, annually-resolved, spatial reconstruction of the European summer (June–August) temperature fields back to 755 CE based on Bayesian hierarchical modelling (BHM), together with estimates of the European mean temperature variation since 138 BCE based on BHM and composite-plus-scaling (CPS). Our reconstructions compare well with independent instrumental and proxy-based temperature estimates, but suggest a larger amplitude in summer temperature variability than previously reported. Both CPS and BHM reconstructions indicate that the mean 20th century European summer temperature was not significantly different from some earlier centuries, including the 1st, 2nd, 8th and 10th centuries CE. The 1st century (in BHM also the 10th century) may even have been slightly warmer than the 20th century, but the difference is not statistically significant. Comparing each 50 yr period with the 1951–2000 period reveals a similar pattern. Recent summers, however, have been unusually warm in the context of the last two millennia and there are no 30 yr periods in either reconstruction that exceed the mean average European summer temperature of the last 3 decades (1986–2015 CE). A comparison with an ensemble of climate model simulations suggests that the reconstructed European summer temperature variability over the period 850–2000 CE reflects changes in both internal variability and external forcing on multi-decadal time-scales. For pan-European temperatures we find slightly better agreement between the reconstruction and the model simulations with high-end estimates for total solar irradiance. Temperature differences between the medieval period, the recent period and the Little Ice Age are larger in the reconstructions than the simulations. This may indicate inflated variability of the reconstructions, a lack of sensitivity and processes to changes in external forcing on the simulated European climate and/or an underestimation of internal variability on centennial and longer time scales. %0 conference lecture %@ %A Jung, F. %D 2016 %J RegMed Forum - 10 Jahre BCRT %N %P %T Hemocompatibility of Biomaterials - Towards a Personalized Approach %U %X %0 conference lecture %@ %A Braune, S.,Sperling, C.,Maitz, M.F.,Steinseifer, U.,Clauser, J.,Hiebl, B.,Krajewski, S.,Wendel, H.P.,Jung, F. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Thrombogenicity testing of polymers: Round-robin study to assess inter-center variability %U %X %0 conference lecture %@ %A Jung, F.,Krueger-Genge, A.,Braune, S.,Ma, N.,Lendlein, A. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Biological Evaluation of polymer-based Biomaterials %U %X %0 conference lecture %@ %A Maier, A.,Braune, S.,Lendlein, A.,Jung, F. %D 2016 %J 35th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Adsorption and conformational changes of the human von Willebrand factor on polymer-based biomaterials %U %X %0 conference lecture %@ %A Blocki, A.,Wang, Y.,Koch, M.,Jung, F.,Bhakoo, K.,Raghunath, M.,Lendlein, A. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Blood-derived angiogenic cells (BDACs) resemble a hematopoietic pericyte population and are a promosing candidate for therapeutic angiogenesis %U %X %0 conference lecture %@ %A Schulz, C.,Krueger-Genge, A.,Vukicevic, R.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Monolayer formation and shear-resistance of human vein endothelial cells on gelatin-based hydrogels with tailorable elasticity and degradability %U %X %0 conference poster %@ %A Baeckemo-Johansson, J.,Reinthaler, M.,Braune, S.,Lendlein, A.,Jung, F. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T Shear-induces platelet adherence and activation in a dynamic multiwell-plate system %U %X %0 conference lecture %@ %A Braune, S.,Baeckemo-Johansson, J.,Kratz, K.,Jung, F.,Lendlein, A. %D 2016 %J 18th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2016 %N %P %T The Influence of different rewetting procedures on the thrombogenicity of nanoporous poly(ether imide) microparticles %U %X %0 editorial %@ 1743-4440 %A Reinthaler, M.,Jung, F.,Landmesser, U.,Lendlein, A. %D 2016 %J Expert Review of Medical Devices %N 11 %P 1001-1003 %R doi:10.1080/17434440.2016.1230013 %T Editorial: Trend to move from permanent metals to degradable, multifunctional polymer or metallic implants in the example of coronary stents %U https://doi.org/10.1080/17434440.2016.1230013 11 %X No abstract %0 conference lecture %@ %A Maier, A.,Braune, S.,Lendlein, A.,Jung, F. %D 2016 %J Multifunctional Biomaterials for Medicine, HVI Symposium 2016 %N %P %T Adsorption and conformational changes of the human von Willebrand factor on polymer-based biomaterials %U %X %0 journal article %@ 1616-5187 %A Schulz, C.,Hecht, J.,Krueger-Genge, A.,Kratz, K.,Jung, F.,Lendlein, A. %D 2016 %J Macromolecular Bioscience %N 12 %P 1776-1791 %R doi:10.1002/mabi.201600319 %T Generating Aptamers Interacting with Polymeric Surfaces for Biofunctionalization %U https://doi.org/10.1002/mabi.201600319 12 %X Common strategies for biofunctionalization of surfaces comprise the immobilization of bioactive molecules used as cell-binding ligands for cell recruitment. Besides covalent binding, multivalent noncovalent physical forces between substrate and ligand are an alternative way to equip surfaces with biomacromolecules. In this study, polymer binding ligands are screened by means of a DNA-based in vitro selection process. As candidate biomaterials poly(ether imide) (PEI), polystyrene, and poly[ethylene-co-(vinyl acetate)] are selected, due to their different chemical structure, but similar macroscopic interface properties, allowing physical interaction with nucleotide bases by varying valences. Multivalent interacting aptamers are successfully enriched by SELEX method and an area-wide surface functionalization is achieved, which can be used for further binding of bioactive molecules. In vitro selection against the polymers result in thymine-dominated aptamer binding motifs. The preferential interaction with thymine is attributed to its chemical structure, connected with a decreased electrostatic repulsion of the π-system and the hydrophobic character maximizing entropy. The aptamer binding stability correlates with available valences for interaction, resulting in a more stable functionalization of PEI. %0 conference lecture %@ %A Tondera, C.,Ullm, S.,Krüger-Genge, A.,Jung, F.,Gebauer, T.,Neffe, A.,Lendlein, A.,Steinbach, J.,Pietzsch, J. %D 2016 %J World Biomaterials Congress (WBC 2016) %N %P %T Gelatin-based hydrogels as versatile tools for tissue engineering: insights from multimodal imaging in vivo and ex vivo %U %X %0 journal article %@ 1079-5642 %A Hytoenen, J.,Leppaenen, O.,Braesen, J.H.,Schunck, W.-H.,Mueller, D.,Jung, F.,Mrowietz, C.,Jastroch, M.,Bergwelt-Baildon, M.V.,Kappert, K.,Heuser, A.,Drenckhahn, J.-D.,Pieske, B.,Thierfelder, L.,Ylae-Herttuala, S.,Blaschke, F. %D 2016 %J Arteriosclerosis, Thrombosis, and Vascular Biology : ATVB %N 8 %P 1534-1548 %R doi:10.1161/ATVBAHA.115.306962 %T Activation of Peroxisome Proliferator–Activated Receptor-Delta as Novel Therapeutic Strategy to Prevent In-Stent Restenosis and Stent Thrombosis %U https://doi.org/10.1161/ATVBAHA.115.306962 8 %X Objective—Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator–activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement.,Approach and Results—Here, we report that PPARδ ligand–coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor–stimulated proliferation and migration.,Conclusions—In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes. %0 conference poster %@ %A Kaessmeyer, S.,Sehl, J.,Khiao In, M.,Hiebl, B.,Jung, F.,Franke, R.,Plendl, J. %D 2016 %J 35. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Effekt von Röntgenkontrastmitteln auf die in vitro Angiogenese mikrovaskulärer Endothelzellen in 3-dimensionalen organtypischen Kokulturen %U %X %0 journal article %@ 1838-7640 %A Tondera, C.,Hauser, S.,Krueger-Genge, A.,Jung, F.,Neffe, A.T.,Lendlein, A.,Klopfleisch, R.,Steinbach, J.,Neuber, C.,Pietzsch, J. %D 2016 %J Theranostics %N 12 %P 2114-2128 %R doi:10.7150/thno.16614 %T Gelatin-based Hydrogel Degradation and Tissue Interaction in vivo: Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice %U https://doi.org/10.7150/thno.16614 12 %X Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue. %0 conference lecture %@ %A Blocki, A.,Koch, M.,Beyer, S.,Lendlein, A.,Jung, F. %D 2016 %J 35. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Angiogenesis during wound healing: an in vitro model %U %X %0 journal article %@ 1752-0894 %A Buentgen, U.,Myglan, V.S.,Ljungqvist, F.C.,McCormick, M.,Di Cosmo, N.,Sigl, M.,Jungclaus, J.,Wagner, S.,Krusic, P.J.,Esper, J.,kaplan, J.O.,de Vaan, M.A.C.,Luterbacher, J.,Wacker, L.,Tegel, W.,Solomina, O.N.,Nicolussi, K.,Oppenheimer, C.,Reinig, F.,Kirdyanov, A.V. %D 2016 %J Nature Geoscience %N %P 231-236 %R doi:10.1038/ngeo2652 %T Cooling and societal change during the Late Antique Little Ice Age from 536 to around 660 AD %U https://doi.org/10.1038/ngeo2652 %X Climatic changes during the first half of the Common Era have been suggested to play a role in societal reorganizations in Europe1, 2 and Asia3, 4. In particular, the sixth century coincides with rising and falling civilizations1, 2, 3, 4, 5, 6, pandemics7, 8, human migration and political turmoil8, 9, 10, 11, 12, 13. Our understanding of the magnitude and spatial extent as well as the possible causes and concurrences of climate change during this period is, however, still limited. Here we use tree-ring chronologies from the Russian Altai and European Alps to reconstruct summer temperatures over the past two millennia. We find an unprecedented, long-lasting and spatially synchronized cooling following a cluster of large volcanic eruptions in 536, 540 and 547 AD (ref. 14), which was probably sustained by ocean and sea-ice feedbacks15, 16, as well as a solar minimum17. We thus identify the interval from 536 to about 660 AD as the Late Antique Little Ice Age. Spanning most of the Northern Hemisphere, we suggest that this cold phase be considered as an additional environmental factor contributing to the establishment of the Justinian plague7, 8, transformation of the eastern Roman Empire and collapse of the Sasanian Empire1, 2, 5, movements out of the Asian steppe and Arabian Peninsula8, 11, 12, spread of Slavic-speaking peoples9, 10 and political upheavals in China13. %0 journal article %@ 1386-0291 %A Krueger-Genge, A.,Jung, F.,Fuhrmann, R.,Franke, R.-P. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 867-874 %R doi:10.3233/CH-168051 %T Effects of different components of the extracellular matrix on endothelialization %U https://doi.org/10.3233/CH-168051 4 %X The endothelialization of cardiovascular prostheses is known to improve their haemocompatibility. As such body-foreign materials often do not endothelialize spontaneously. A lot of in vitro studies are ongoing how endothelialization of biomaterials can be improved. In this study the influence of different components of a tissue-typical extracellular matrix (ECM) like laminin, fibronectin or gelatin on the formation of an endothelial cell monolayer and on the shear resistance of adherent cells on these substrates was studied.The study revealed that the density of human venous endothelial cells (HUVEC) monolayers differed markedly between cells grown on a natural ECM and cells grown on singularized components of an ECM (p < 0.001). Only HUVEC grown on laminin showed similar densities and a stress fiber pattern comparable to HUVEC grown on the ECM. HUVEC grown on gelatin- or fibronectin-coated coverslips were less firmly attached to the substrate; frequently individual HUVEC and even groups of cells detached.Concluding it seems that coating of implants with laminin supports the formation of shear resistant endothelial cell (EC) monolayer - superior to other ECM components. %0 journal article %@ 1386-0291 %A Schulz, C.,Vukicevic, R.,Krueger-Genge, A.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2016 %J Clinical Hemorheology and Microcirculation %N 4 %P 699-710 %R doi:10.3233/CH-168007 %T Monolayer formation and shear-resistance of human umbilical vein endothelial cells on gelatin-based hydrogels with tailorable elsticity and degradability %U https://doi.org/10.3233/CH-168007 4 %X The formation of a functionally-confluent and shear-resistant endothelial cell monolayer on cardiovascular implants is a promising strategy to prevent thrombogenic processes after implantation. On the basis of existing studies with arterial endothelial cells adhering after two hours on gelatin-based hydrogels in marked higher numbers compared to tissue culture plates, we hypothesize that also venous endothelial cells (HUVEC) should be able to adhere and form an endothelial monolayer on these hydrogels after days. Furthermore, variation of the hydrogel composition, which slightly influences the materials elasticity and even more the degradation behaviour, should have no considerable effect on HUVEC. Therefore, the monolayer formation and shear resistance of HUVEC were explored on two gelatin-based hydrogels differing in their elasticity (Young’s moduli between 35 and 55 kPa) in comparison to a positive control (HUVEC on glass cover slips) and a negative control (HUVEC on glass cover slips activated with interleukin-1β) after 9 days of culturing. HUVEC density after 9 days of culturing under static conditions was lower on the hydrogels compared to both controls (p < 0.05 each). On G10_LNCO8 slightly more EC adhered than on G10_LNCO5. Staining of the actin cytoskeleton and VE-cadherin revealed a pronounced cell-substrate interaction while the cell-cell interaction was comparable to the controls (HUVEC on glass). The secretion of vasoactive and inflammatory mediators did not differ between the hydrogels and the controls. Adherent HUVEC seeded on the hydrogels were able to resist physiological shear forces and the release of cyto- and chemokines in response to the shear forces did not differ from controls (HUVEC on glass). Therefore, both gelatin-based hydrogels are a suitable substrate for EC and a promising candidate for cardiovascular applications. %0 journal article %@ 1386-0291 %A Krueger, A.,Fuhrmann, R.,Jung, F.,Franke, R.P. %D 2015 %J Clinical Hemorheology and Microcirculation %N 2 %P 151-156 %R doi:10.3233/CH-151992 %T Morphology of primary human venous endothelial cell cultures before and after culture medium exchange %U https://doi.org/10.3233/CH-151992 2 %X BACKGROUND: Platelet adhesion to artificial surfaces is one of the most important indicators for the thrombogenicity of implant materials. Currently, a variety of enzyme activity-based colorimetric assays or microscopy-based techniques are commonly in use to assess this characteristic. Studies about how data of colorimetric assays correlate with the image-based quantification of adherent platelets are scarce. To address this question, the present study compared two colorimetric assays (lactate dehydrogenase (LDH) and acid phosphatase (ACP)) with an image-based quantification of the density of platelets adhering on polymer-based biomaterial surfaces.,MATERIALS AND METHODS: Tri-sodium citrated whole blood was collected from apparently healthy subjects and platelet rich plasma (PRP) was prepared according to a standardized protocol. An in vitro static thrombogenicity test was applied to study platelet adhesion from PRP adjusted to 50,000 platelets per μL on three different polymers: medical grade polytetrafluoroethylene (PTFE), silicone and polyethylene terephthalate (PET). For the direct image-based approach, surface adherent platelets were fixed, fluorescently labelled and microscopically visualized. The image-based determination of platelet densities provided reference values for the comparison with data of the colorimetric assays. Correlation between standard platelet concentrations and ACP/LDH absorbance measurements were analysed to estimate accuracy and association of both parameters. ACP and LDH release from resting and ADP-stimulated platelets was studied to estimate how platelet activation influences colorimetric assay results.,RESULTS: The density of adherent platelets ranged from 15,693 ± 2,487 platelets·mm–2 (PTFE) to 423 ± 99 platelets·mm–2 (silicone) and 4,621 ± 1,427 platelets·mm–2 (PET) and differed significantly between the three polymers (ANOVA: p <  0.05). Correlation coefficients between microscopic and colorimetric determination of platelet densities ranged between r = 0.93 (LDH, p <  0.001) and r = 0.94 (ACP, p <  0.001). ACP absorbance measurements of platelet standards with different concentrations corresponded well to an ideal linear regression, while LDH data either deceeded or exceeded the expected values. The LDH release during ADP-induced platelet activation was significantly higher compared to the release of ACP.,CONCLUSION: For an adjusted platelet concentration of 50,000 platelets· μL–1, both colorimetric assays (ACP and LDH) allowed a similar accurate quantification of the mean platelet density compared to the microscopic evaluation. Better linearity of the assay standards, less variability of the results and a lower influence of platelet activation on the measurements mark the ACP assay as more suitable for the assessment of material surface adherent platelets compared to the LDH assay, particularly, if near physiological platelet concentrations are applied. %0 conference lecture %@ %A Hiebl, B.,Nennig, E.,Schiestel, S.,Kovacs, A.,Jung, F.,Fischer, H. %D 2015 %J 34th Conference of the German Society for Clinical Microcirculation and Hemorheology %N %P %T Biocompatibility of a novel zinc stent with a closed-cell-design %U %X %0 journal article %@ 1386-0291 %A Hiebl, B.,Nennig, E.,Schiestel, S.,Kovacs, A.,Jung, F.,Fischer, H. %D 2015 %J Clinical Hemorheology and Microcirculation %N 2 %P 205-211 %R doi:10.3233/CH-151983 %T Biocompatibility of a novel zinc stent with a closed-cell-design %U https://doi.org/10.3233/CH-151983 2 %X Biomaterials made of zinc have been widely described to be antioxidative, hypothrombogenic, antiinflammatory and antiproliferative. Additionally in vivo zinc is toxic only in high concentrations and can completely be metabolized in vivo. Due to these properties zinc based vascular stents might be able to reduce the rate of restenosis in comparison to bare metal stents and zinc stents might be also able to limit the foreign body reaction. In the presented study we tested the biocompatibility and degradability of a stent made of zinc and characterized by a closed-cell-design to achieve high opening force and to increase stent stiffness. After 100 days of enzymatic and hydrolytic degradation in 15 ml blood serum (fetal calf serum) a significant loss of weight (1.72 wt% ) was measured. Zinc was compared to other metals in terms of degradation rates. After six weeks of incubation in physiologic sodium chloride solution zinc showed the slowest degradation time, 6 times less than stainless steel and 4 times less than magnesium. In the tests for cytotoxic effects the degraded zinc stent caused no changes in the LDH-release and cell membrane integrity (3T3 cells, mouse fibroblasts) respectively, in the cell activity/proliferation (MTS assay) and in the morphological characteristics of the cells and cell layers in comparison to the control material (polystyrene). Based on these results the tested zinc stent proved to be non-cytotoxic and to be characterized by degradation characteristics which might be advantageous in comparison to magnesium and stainless steel. %0 conference poster %@ %A Tzoneva, R.,Uzunova, V.,Apostolova, S.,Krüger, A.,Neffe, A.,Jung, F.,Lendlein, A. %D 2015 %J 34. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Effect of electrical stimulation on vascular endothelial and tumor cells on angiogenic response %U %X %0 journal article %@ 0391-3988 %A Braune, S.,Zhou, S.,Groth, B.,Lendlein, A.,Jung, F. %D 2015 %J The International Journal of Artificial Organs %N 7 %P 345-418 %R doi:10.5301/ijao.5000417 %T Quantification of adherent platelets on biomaterials. Comparison of colorimetric and microscopic assessment %U https://doi.org/10.5301/ijao.5000417 7 %X No abstract %0 conference lecture %@ %A Braune, S.,Zhou, S.,Groth, B.,Lendlein, A.,Jung, F. %D 2015 %J 42th Annual ESAO Conference, ESAO 2015 %N %P %T Quantification of adherent platelets on biomaterials. Comparison of colorimetric and microscopic assessment %U %X %0 journal article %@ 1814-9324 %A Fernandez Donado, L.,Gonzalez-Rouco, J.F.,Garcia Bustamante, E.,Goosse, H.,Jungclaus, J.,Bothe, O.,Hegerl, G.,Moberg, A.,Raible, C.C.,Schurer, A.,Wagner, S.,Zorita, E.,Hind, A.,Lehner, F.,McKay, N.,Warren, E.,Widmann, M. %D 2015 %J Climate of the Past %N 12 %P 1673-1699 %R doi:10.5194/cp-11-1673-2015 %T Continental-scale temperature variability in PMIP3 simulations and PAGES 2k regional temperature reconstructions over the past millennium %U https://doi.org/10.5194/cp-11-1673-2015 12 %X Estimated external radiative forcings, model results, and proxy-based climate reconstructions have been used over the past several decades to improve our understanding of the mechanisms underlying observed climate variability and change over the past millennium. Here, the recent set of temperature reconstructions at the continental-scale generated by the PAGES 2k project and a collection of state-of-the-art model simulations driven by realistic external forcings are jointly analysed. The first aim is to estimate the consistency between model results and reconstructions for each continental-scale region over the time and frequency domains. Secondly, the links between regions are investigated to determine whether reconstructed global-scale covariability patterns are similar to those identified in model simulations. The third aim is to assess the role of external forcings in the observed temperature variations. From a large set of analyses, we conclude that models are in relatively good agreement with temperature reconstructions for Northern Hemisphere regions, particularly in the Arctic. This is likely due to the relatively large amplitude of the externally forced response across northern and high-latitude regions, which results in a clearly detectable signature in both reconstructions and simulations. Conversely, models disagree strongly with the reconstructions in the Southern Hemisphere. Furthermore, the simulations are more regionally coherent than the reconstructions, perhaps due to an underestimation of the magnitude of internal variability in models or to an overestimation of the response to the external forcing in the Southern Hemisphere. Part of the disagreement might also reflect large uncertainties in the reconstructions, specifically in some Southern Hemisphere regions, which are based on fewer palaeoclimate records than in the Northern Hemisphere. %0 editorial %@ 2352-3697 %A Jung, F. %D 2015 %J Journal of Cellular Biotechnology %N 1 %P 1-1 %R doi:10.3233/JCB-15011 %T Editorial %U https://doi.org/10.3233/JCB-15011 1 %X No abstract %0 conference lecture %@ %A Hiebl, B.,Engin, S.,Adam, S.,Jung, F.,Fischer, H. %D 2015 %J 34. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Einfluss der Testdauer auf Beurteilung der Hämokompatibilität gemäß EN ISO 10993-4 %U %X %0 journal article %@ 1386-0291 %A Braune, S.,Zhou, S.,Groth, B.,Jung, F. %D 2015 %J Clinical Hemorheology and Microcirculation %N 2 %P 225-236 %R doi:10.3233/CH-151995 %T Quantification of adherent platelets on polymer-based biomaterials. Comparison of colorimetric and microscopic assessment %U https://doi.org/10.3233/CH-151995 2 %X BACKGROUND: Platelet adhesion to artificial surfaces is one of the most important indicators for the thrombogenicity of implant materials. Currently, a variety of enzyme activity-based colorimetric assays or microscopy-based techniques are commonly in use to assess this characteristic. Studies about how data of colorimetric assays correlate with the image-based quantification of adherent platelets are scarce. To address this question, the present study compared two colorimetric assays (lactate dehydrogenase (LDH) and acid phosphatase (ACP)) with an image-based quantification of the density of platelets adhering on polymer-based biomaterial surfaces.,MATERIALS AND METHODS: Tri-sodium citrated whole blood was collected from apparently healthy subjects and platelet rich plasma (PRP) was prepared according to a standardized protocol. An in vitro static thrombogenicity test was applied to study platelet adhesion from PRP adjusted to 50,000 platelets per μL on three different polymers: medical grade polytetrafluoroethylene (PTFE), silicone and polyethylene terephthalate (PET). For the direct image-based approach, surface adherent platelets were fixed, fluorescently labelled and microscopically visualized. The image-based determination of platelet densities provided reference values for the comparison with data of the colorimetric assays. Correlation between standard platelet concentrations and ACP/LDH absorbance measurements were analysed to estimate accuracy and association of both parameters. ACP and LDH release from resting and ADP-stimulated platelets was studied to estimate how platelet activation influences colorimetric assay results.,RESULTS: The density of adherent platelets ranged from 15,693 ± 2,487 platelets·mm–2 (PTFE) to 423 ± 99 platelets·mm–2 (silicone) and 4,621 ± 1,427 platelets·mm–2 (PET) and differed significantly between the three polymers (ANOVA: p <  0.05). Correlation coefficients between microscopic and colorimetric determination of platelet densities ranged between r = 0.93 (LDH, p <  0.001) and r = 0.94 (ACP, p <  0.001). ACP absorbance measurements of platelet standards with different concentrations corresponded well to an ideal linear regression, while LDH data either deceeded or exceeded the expected values. The LDH release during ADP-induced platelet activation was significantly higher compared to the release of ACP.,CONCLUSION: For an adjusted platelet concentration of 50,000 platelets· μL–1, both colorimetric assays (ACP and LDH) allowed a similar accurate quantification of the mean platelet density compared to the microscopic evaluation. Better linearity of the assay standards, less variability of the results and a lower influence of platelet activation on the measurements mark the ACP assay as more suitable for the assessment of material surface adherent platelets compared to the LDH assay, particularly, if near physiological platelet concentrations are applied. %0 journal article %@ 2352-3697 %A Franke, R.P.,Fuhrmann, R.,Krueger, A.,Jung, F. %D 2015 %J Journal of Cellular Biotechnology %N 1 %P 119-130 %R doi:10.3233/JCB-15012 %T Reaction of arterial endothelial cells to stent impression: In vitro study using a model of the human artery wall %U https://doi.org/10.3233/JCB-15012 1 %X Stenoses in arterial blood vessels by artherosclerotic processes can decrease the supply of downstream tissue dramatically. The implantation of stents by percutaneous coronary intervention is one method of choice to restore the physiological blood flow. In some cases in-stent re-stenoses by thrombotic events, vascular wall hyperplasia or endothelial dysfunction occur. Causes and nature underlying this processes are not fully understood.,Aim of the present study was to study the re-stenotic processes after stent impress on a cellular and molecular level in vitro. Therefore, human arterial endothelial cells (HUAEC) were seeded on a model vascular wall intima consisting of extracellular matrix secreted by bovine corneal endothelial cells. Subsequently, a pre-mounted balloon-expendable tubular stent made of 316 L was impressed through the HUAEC layer leading to an impairment of the vessel wall intima. After stent removal the wound healing process, HUAEC membrane integrity, vitality, proliferation and function were assessed.,Immediately after stent impress an increased level of lactate dehydrogenase (LDH) was observed indicating an impairment of the cell membrane integrity. After 24 h baseline LDH values presented again. HUAEC vitality adjacent to the stent impress induced wound was normal (investigated by inverted microscopy). The proliferation of HUAEC was the highest in the direct vicinity of the stent impress induced wound. Prostacyclin and nitric oxide decreased significantly indicating a temporary loss of cell function.,These results could imply that the healing process of the endothelial cell lesion is superior to the maintenance of vascular tonicity and downregulation of platelet aggregation. %0 conference lecture %@ %A Behr, S.,Glane, S.,Koellner, A.,Jungblut, L.,Scheider, I.,Bargmann, S.,Schneider, G.A. %D 2015 %J 6th International Conference on Mechanics of Biomaterials and Tissues 2015 %N %P %T Nacre-inspired laminates of laser-perforated zirconia %U %X %0 conference lecture %@ %A Braune, S.,Jung, F.,Lendlein, A. %D 2015 %J Exkursion: Biotechnologiestudenten der TU  Berlin; Prof. Lauster AG %N %P %T Hämokompatibilität / Endothelialisierung von Biomaterialien %U %X %0 conference lecture %@ %A Braune, S.,Zhou, S.,Groth, B.,Lendlein, A.,Jung, F. %D 2015 %J XLII Annual ESAO Conference %N %P %T Quantification of adherent platelets on polymer-based biomaterials. Comparison of colorimetric and microscopic assessment %U %X %0 journal article %@ 1386-0291 %A Krueger, A.,Fuhrmann, R.,Jung, F.,Franke, R.-P. %D 2015 %J Clinical Hemorheology and Microcirculation %N 1 %P 153-161 %R doi:10.3233/CH-151943 %T Influence of the coating with extracellular matrix and the number of cell passages on the endothelialization of a polystyrene surface %U https://doi.org/10.3233/CH-151943 1 %X The proper morphology and function of the vascular endothelium are prerequisites for a sufficient supply of the tissues. Endothelial cell (EC) dysfunction can lead to circulatory disorders and the development of cardiovascular diseases. The endothelialization of cardiovascular implants is a sophisticated task since EC miss their natural environment and physiological stimuli in vitro. In addition, different studies revealed that the EC behavior and morphology depended on the substrate and the passage number of the EC. Therefore, the comparison of endothelialization studies is very difficult, when passage and substrate are unknown. The aim of this study was to investigate the growth potential and cell morphology of human venous endothelial cells (HUVEC) as a function of different cell passages and different substrates (pristine polystyrene, tissue-typical ECM-coated polystyrene). The study revealed that HUVEC morphology and growth potential were significantly different on pristine polystyrene compared to the basal lamina-like ECM-coated polystyrene surface. Furthermore, it became obvious that the passage of the cells affected the endothelialization of the polystyrene surface significantly. In conclusion, this study emphasized the need for a critical consideration of EC data whereas a simple comparison of results is not possible if EC age and passage is unknown. %0 conference lecture %@ %A Braune, S.,Jung, F.,Lendlein, A. %D 2015 %J VDI Arbeitskreis Kunststofftechnik Kunststoffe in der Medizin %N %P %T Thrombogenität und Hämokompatibilität von Biomaterialien %U %X %0 conference lecture %@ %A Braune, S.,Kratz, K.,Lendlein, A.,Jung, F. %D 2015 %J 34. Jahrestagung der Deutschen Gesellschaft für klinische Mikrozirkulation und Hämorheologie (DGKMH) %N %P %T Strategy for the hemocompatibility testing of polymer based microparticles %U %X %0 journal article %@ 1753-9447 %A Gori, T.,Wild, P.S.,Schnabel, R.,Schulz, A.,Pfeiffer, N.,Blettner, M.,Beutel, M.E.,Forconi, S.,Jung, F.,Lackner, K.J.,Blankenberg, S.,Muenzel, T. %D 2015 %J Therapeutic Advances in Cardiovascular Disease %N 6 %P 354-365 %R doi:10.1177/1753944715589887 %T The distribution of whole blood viscosity, its determinants and relationship with arterial blood pressure in the community: cross-sectional analysis from the Gutenberg Health Study %U https://doi.org/10.1177/1753944715589887 6 %X Background: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study.,Methods and results: Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, min–max: 35–74 years old; 49.5% women) from the Gutenberg Health Study as well as in a subgroup of 3223 subjects (61.1% women, mean age 49.2, min–max 35–74 years old) without risk factors or self-reported cardiovascular disease. Age- and gender-adjusted mean values for viscosity were defined. Regression models showed a relationship between classical risk factors and blood viscosity measures; the overall R 2 of the multiple linear regression model was however as low as 0.067 and 0.049 for high and low shear stress viscosity, respectively. After correction for cardiovascular risk factors, there was a very mild association between viscosity and prevalent coronary artery disease and heart failure. Systolic, mean and diastolic blood pressure increased with increasing blood viscosity after correction for age and gender.,Conclusions: We provide reference values for viscosity in a population-based cohort. Blood viscosity decreases in older subjects and shows a very mild association with cardiovascular risk factors and prevalent disease in our cohort. There is a linear positive association between viscosity and blood pressure. %0 journal article %@ 1386-0291 %A Schulz, C.,Ruesten-Lange, M.v.,Krueger, A.,Lendlein, A.,Jung, F. %D 2014 %J Clinical Hemorheology and Microcirculation %N 2 %P 147-158 %R doi:10.3233/CH-141826 %T Adherence and shear-resistance of primary human endothelial cells on smooth poly(ether imide) films %U https://doi.org/10.3233/CH-141826 2 %X BACKGROUND: Occlusions of artificial small-diameter cardiovascular grafts are frequent events after implantation, often caused by clot formations. A main factor is the insufficient hemocompatibility of the inner artificial graft surface, which could be improved by endothelialization. Therefore, one challenge in cardiovascular graft engineering is the establishment of a shear-resistant endothelial cell layer to prevent cell detachment by shear forces after implantation. MATERIALS AND METHODS: Recently, very smooth (Rq = 2.37 ± 1.40 nm) poly(ether imide) (PEI) films were introduced as a biocompatible candidate material for cardiovascular devices. In this study the stability of primary human umbilical vein endothelial cell (HUVEC) monolayer was investigated after long-term seeding (9 days) on PEI-films and subsequent exposure to a venous shear stress of 3 dyn/cm2 for up to 6 hours using the cone-and-plate shearing technique. Cell density, growth pattern and morphology of HUVEC were determined prior and after shearing compared to glass as control substrate. HUVEC adhering to the substrate after shear stress were counted and analyzed by fluorescent staining. Supernatants were collected and secretion profile analysis of vasoactive and inflammatory mediators was performed. RESULTS: The cell density on PEI-films compared to the controls was slightly higher after long-term seeding and exposure to shear stress (glass: 71,656 ± 8,830 cells/cm2 and 42,239 ± 5,607 cells/cm2; PEI-film: 64,056 ± 2,829 cells/cm2 and 45,422 ± 2,507 cells/cm2 before and after shear stress, respectively). Actin- and vinculin-staining revealed a scattered re-organization of the cytoskeleton as well as a formation of stress fibers and focal adhesion points. Secretion of prostacyclin and thromboxane A2 was increased after application of shear stress, but no significant differences were detectable between cells growing on PEI-films or glass. Amounts of secreted inflammatory cytokines IL-6 and IL-8 in the supernatant were significantly lower for HUVEC seeded on PEI-films compared to glass before as well as after stress. CONCLUSION: The study demonstrated that HUVEC were able to resist exposure to venous shear stress when seeded on smooth PEI-films with typical morphology and adhesion behavior. However, HUVEC adherence on PEI was not yet sufficient to retain a complete cell monolayer after shear stress exposure. Occasionally, single cells or cell plaques were disrupted resulting in cell free areas in the confluent HUVEC layer. Apart from this our data suggest that PEI is a suitable substrate for HUVEC under static and dynamic conditions and therefore a promising candidate material for cardiovascular applications. The next objective is a surface functionalization of the PEI-films in a cell specific manner to reach a functionally confluent, shear resistant HUVEC monolayer. %0 conference lecture %@ %A Roch, T.,Akymenko, O.,Krueger, A.,Jung, F.,Ma, N.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Expression pattern analysis and activity determination of matrix metalloproteinase derived from human macrophage subsets %U %X %0 editorial %@ 1386-0291 %A Jung, F.,Gori, T. %D 2014 %J Clinical Hemorheology and Microcirculation %N 2 %P 93-94 %R doi:10.3233/CH-141819 %T Editorial: Has Science started to go wrong? %U https://doi.org/10.3233/CH-141819 2 %X No abstract %0 journal article %@ 1386-0291 %A Gerk, U.,Krueger, A.,Franke, R.P.,Jung, F. %D 2014 %J Clinical Hemorheology and Microcirculation %N 1 %P 171-174 %R doi:10.3233/CH-141879 %T Effect of radiographic contrast media (Iodixanol, Iopromide) on hemolysis %U https://doi.org/10.3233/CH-141879 1 %X Radiographic contrast media can lead to drastic changes of the morphology of erythrocytes. The change of the erythrocyte morphology is associated with a decreased deformability possibly resulting from distinctions in the loss of constituents of the membrane cytoskeleton. However, it is unclear whether there is an intravascular hemolysis as a consequence of the disintegration of the erythrocyte membrane. The results of this study showed, that free haemoglobin increased from 16.8 ± 10.0 mg/dl to 21.6 ± 12.6 mg/dl after Iopromide application (p = 0.240), while it slightly decreased from 20.5 ± 10.3 mg/dl to 19.5 ± 12.2 mg/dl after Iodixanol application (p = 0.547). The slight decrease of free haemoglobin after application of Iodixanol differed significantly compared to the increase of free haemoglobin after Iopromide application (p < 0.05). This different response is thought to give evidence to the assumption that the erythrocyte membrane integrity was compromised leading to the release of free haemoglobin as an indicator of hemolysis as well. %0 conference lecture %@ %A Krueger, A.,Dietze, S.,Kratz, K.,Jung, F.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Endothelial cell migration on different polymer-based biomaterials %U %X %0 conference lecture %@ %A Walter, M.,Braune, S.,Schulze, F.,Lendlein, A.,Jung, F. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Platelet morphology and function during storage up to 24 hours %U %X %0 conference poster %@ %A Zhou, S.,Braune, S.,Groth, B.,Lendlein, A.,Jung, F. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Quantification of adherent platelet densities on different substrates by lactate dehydrogenase and acid phosphatase assays in comparison to an image-based analysis %U %X %0 journal article %@ 1386-0291 %A Hiebl, B.,Hopperdietzel, C.,Hueningen, H.,Dietze, K.,Jung, F.,Niehues, S.M. %D 2014 %J Clinical Hemorheology and Microcirculation %N 1 %P 107-113 %R doi:10.3233/CH-141881 %T Tissue reaction induced by implanted venous access ports in adult patients after infection of the implantation site %U https://doi.org/10.3233/CH-141881 1 %X Implantable long-term central venous port systems (CVPS) are widely used as a permanent means of accessing the vascular system for intravenous delivery of drugs, parenteral nutrition, blood transfusion, and blood sampling. These systems allow easy and repetitive puncture without causing much damage to the vessels. However, the body foreign surface of CVPS induces an inflammatory response with varying intensity (depending on the implant materials) that leads to formation of a fibrous tissue capsule around the implant. This study was designed to investigate the influence of bacterial infection on the tissue reaction induced by implanted CVPS in adult patients. 20 patients (9 women, 11 men, 58 ± 14 yrs of age) were included in this study. These patients received explantation of a polysulfone based CVPS (ChemoSite™, Covidien, Mansfield, USA) due to port related infections (patients with bacterial infections at the implantation site: group A, 5 men, 1 women) or to other reasons such as termination of treatment, thrombosis, or CVPS dysfunction (patients without bacterial infections, group B, 6 men, 8 women) 299.9 ± 261.2 days after CVPS implantation. A sample of the encapsulating tissue covering the CVPS together with surrounding tissue (at least 1 × 1 cm2) was placed in a small container with fixing agent, a buffered neutral 4% formalin solution (pH 7). Histological sections of the samples were prepared for light microscopic analysis after paraffin embedding. Sections of 3 μm were cut and stained with haematoxylin and eosin, Weigert's elastic stain, and Heidenhain's azan stain. There was no difference in thickness, collagen and elastin content, or cell and capillary density of the fibrous capsule between both groups. Due to the wound healing reaction involving angiogenesis and fibroblast activation cell density and number of capillaries in the capsule tissue of all patients showed a positive correlation (r = 0.45, p < 0.05). However, the study demonstrated that at the end of the foreign body reaction the artificial tissue layer which covers the CVPS after implantation due to foreign body reaction shows only low reactivity towards infections. %0 journal article %@ 0167-5273 %A Park, J.-W.,Sherif, M.A.,Zintl, K.,Lam, Y.-Y.,Goedde, M.,Scharnweber, T.,Jung, F.,Franke, R.P.,Brachmann, J. %D 2014 %J International Journal of Cardiology %N 3 %P 957-963 %R doi:10.1016/j.ijcard.2014.09.194 %T Percutaneous left atrial appendage closure with a novel self-modelizing device: A pre-clinical feasibility study %U https://doi.org/10.1016/j.ijcard.2014.09.194 3 %X The aim of the study is to evaluate the feasibility and safety of a new left atrial appendage (LAA) occluder.,Twelve pigs were included. In 2 pigs the implantation process failed due to pericardial tamponade in 1 pig and device embolization in the other pig. The placement of the devices was controlled via TEE and fluoroscopy. After 6 weeks of implantation the hearts were explanted.,The devices were found to be easy to deploy and showed a very good adaptation to the LAA tissue. Eight out of 10 pigs had full closure of the LAA directly after implantation.,After six weeks, due to the self-modelizing properties of the device, all pigs had a full closure of the LAA. The macroscopic evaluation of the explanted hearts showed that all devices were securely integrated in LAA tissues.,There was one case of mild pericarditis but no macroscopic signs of inflammation on the device surrounding endocardium. The explantation revealed that device loops had penetrated the LAA tissue in three pigs. However, no signs of bleeding, pericardial effusion, or other damage to the LAA wall could be detected and the pigs were in good condition with normal weight gain and no clinical symptoms.,The Occlutech® LAA occluder achieved complete closure of the LAA in all pigs, and remained in the LAA, with benign healing and no evidence of new thrombus or damage to surrounding structures. Moreover, the uncompromised survival of all implanted pigs demonstrates the feasibility and safety of the device. %0 journal article %@ 1386-0291 %A Franke, R.P.,Scharnweber, T.,Fuhrmann, R.,Mrowietz, C.,Wenzel, F.,Krueger, A.,Jung, F. %D 2014 %J Clinical Hemorheology and Microcirculation %N 1 %P 49-63 %R doi:10.3233/CH-141894 %T Radiographic contrast media alterate the localization of actin/band4.9 in the membrane cytoskeleton of human erythrocytes %U https://doi.org/10.3233/CH-141894 1 %X Different radiographic contrast media (RCM) were shown to induce morphological changes of blood cells (e.g. erythrocytes or thrombocytes) and endothelial cells. The echinocytic shape change of erythrocytes, particularly, affords alterations of the membrane cytoskeleton. The cytoskeleton plays a crucial role for the shape and deformability of the red blood cell. Disruption of the interaction between components of the red blood cell membrane cytoskeleton may cause a loss of structural and functional integrity of the membrane. In this study band4.9 and actin as components of the cytoskeletal junctional complex were examined in human erythrocytes after suspension in autologous plasma or in plasma RCM mixtures (30% v/v Iodixanol-320 or Iopromide-370) followed by a successive double staining with TRITC-/FITC-coupled monoclonal antibodies. After adding Iopromide-370 to the plasma in practically none of the cells the rounded conformation of the membrane cytoskeleton – as it appeared in cells suspended in autologous plasma – was found. In addition, Iopromide-370 induced thin lines and coarse knob-like structures of band4.9 at the cell periphery while most cell centers were devoid of band4.9, and a box-like arrangement of bands of band4.9. A dissociation between colours red (actin) and green (band4.9) occurred as well. In contrast, erythrocytes suspended in a plasma/Iodixanol-320 mixture showed a membrane cytoskeleton comparable to cells suspended in autologous plasma, Similar results were found with respect to the distribution of actin. This study revealed for the first time RCM-dependent differences in band4.9 activities as possible pathophysiological mechanism for the chemotoxicity of radiographic contrast media. %0 journal article %@ 1932-6203 %A Franke, R.-P.,Scharnweber, T.,Fuhrmann, R.,Wenzel, F.,Krueger, A.,Mrowietz, C.,Jung, F. %D 2014 %J PLoS One %N 2 %P e89512 %R doi:10.1371/journal.pone.0089512 %T Effect of Radiographic Contrast Media on the Spectrin/Band3-Network of the Membrane Skeleton of Erythrocytes %U https://doi.org/10.1371/journal.pone.0089512 2 %X The membrane of red blood cells consists of a phospholipid bilayer with embedded membrane proteins and is associated on the cytoplasmatic side with a network of proteins, the membrane skeleton. Band3 has an important role as centre of the functional complexes e.g. gas exchange complex and as element of attachment for the membrane skeleton maintaining membrane stability and flexibility. Up to now it is unclear if band3 is involved in the morphology change of red blood cells after contact with radiographic contrast media. The study revealed for the first time that Iopromide induced markedly more severe alterations of the membrane skeleton compared to Iodixanol whose effects were similar to erythrocytes suspended in autologous plasma. A remarkable clustering of band3 was found associated with an accumulation of band3 in spicules and also a sequestration of band3 to the extracellular space. This was evidently accompanied by a gross reduction of functional band3 complexes combined with a dissociation of spectrin from band3 leading to a loss of homogeneity of the spectrin network. It could be demonstrated for the first time that RCM not only induced echinocyte formation but also exocytosis of particles at least coated with band3. %0 journal article %@ 1386-0291 %A Braune, S.,Walter, M.,Schulze, F.,Lendlein, A.,Jung, F. %D 2014 %J Clinical Hemorheology and Microcirculation %N 1 %P 159-170 %R doi:10.3233/CH-141876 %T Changes in platelet morphology and function during 24 hours of storage %U https://doi.org/10.3233/CH-141876 1 %X For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here, we study the influence of whole blood- and PRP-storage times on changes in platelet morphology and function. Blood from apparently healthy subjects was collected according to a standardized protocol and examined immediately after blood collection, four hours and twenty four hours later. The capability of platelets to adhere and form stable aggregates (PFA100, closure time) was examined in sodium citrate anticoagulated whole blood (WB) using the agonists equine type I collagen and epinephrine bitartrate (collagen/epinephrine) as well as equine type I collagen and adenosine-5′-diphosphate (collagen/ADP). Circulating platelets were quantified at each time point. Morphology of platelets and platelet aggregates were visualized microscopically and measured using an electric field multi-channel counting system (CASY). The percentage of activated platelets was assessed by means of P-selectin (CD62P) expression of circulating platelets. Furthermore, platelet factor 4 (PF4) release was measured in platelet poor plasma (PPP) at each time point. Whole blood PFA100 closure times increased after stimulation with collagen/ADP and collagen/epinephrine. Twenty four hours after blood collection, both parameters were prolonged pathologically above the upper limit of the reference range. Numbers of circulating platelets, measured in PRP, decreased after four hours, but no longer after twenty four hours. Mean platelet volumes (MPV) and platelet large cell ratios (P-LCR, 12 fL – 40 fL) decreased over time. Immediately after blood collection, no debris or platelet aggregates could be visualized microscopically. After four hours, first debris and very small aggregates occurred. After 24 hours, platelet aggregates and also debris progressively increased. In accordance to this, the CASY system revealed an increase of platelet aggregates (up to 90 μm diameter) with increasing storage time. The percentage of CD62P positive platelets and PF4 increased significantly with storage time in resting PRP. When soluble ADP was added to stored PRP samples, the number of activatable platelets decreased significantly over storage time. The present study reveals the importance of a consequent standardization in the preparation of WB and PRP. Platelet morphology and function, particularly platelet reactivity to adherent or soluble agonists in their surrounding milieu, changed rapidly outside the vascular system. This knowledge is of crucial interest, particularly in the field of biomaterial development for cardiovascular applications, and may help to define common standards in the in vitro hemocompatibility testing of biomaterials. %0 conference lecture (invited) %@ %A Braune, S.,Jung, F.,Lendlein, A. %D 2014 %J Focus on the Blood-Biomaterial Interface: Surface Analysis meets Blood Compatibility, 74th International IUVSTA Workshop %N %P %T Hemocompatibility testing of biomaterials - Approach for a standardized assessment of thrombogenic surfaces %U %X %0 journal article %@ 0142-9612 %A Ullm, S.,Krueger, A.,Tondera, C.,Gebauer, T.P.,Neffe, A.T.,Lendlein, A.,Jung, F.,Pietzsch, J. %D 2014 %J Biomaterials %N 37 %P 9755-9766 %R doi:10.1016/j.biomaterials.2014.08.023 %T Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties %U https://doi.org/10.1016/j.biomaterials.2014.08.023 37 %X Hydrogels prepared from gelatin and lysine diisocyanate ethyl ester provide tailorable elastic properties and degradation behavior. Their interaction with human aortic endothelial cells (HAEC) as well as human macrophages (Mɸ) and granulocytes (Gɸ) were explored. The experiments revealed a good biocompatibility, appropriate cell adhesion, and cell infiltration. Direct contact to hydrogels, but not contact to hydrolytic or enzymatic hydrogel degradation products, resulted in enhanced cyclooxygenase-2 (COX-2) expression in all cell types, indicating a weak inflammatory activation in vitro. Only Mɸ altered their cytokine secretion profile after direct hydrogel contact, indicating a comparably pronounced inflammatory activation. On the other hand, in HAEC the expression of tight junction proteins, as well as cytokine and matrix metalloproteinase secretion were not influenced by the hydrogels, suggesting a maintained endothelial cell function. This was in line with the finding that in HAEC increased thrombomodulin synthesis but no thrombomodulin membrane shedding occurred. First in vivo data obtained after subcutaneous implantation of the materials in immunocompetent mice revealed good integration of implants in the surrounding tissue, no progredient fibrous capsule formation, and no inflammatory tissue reaction in vivo. Overall, the study demonstrates the potential of gelatin-based hydrogels for temporal replacement and functional regeneration of damaged soft tissue. %0 journal article %@ 0006-355X %A Jung, F.,Krueger, A.,Pindur, G.,Sternitzky, R.,Franke, R.P.,Gori, T. %D 2014 %J Biorheology %N 2-3 %P 207-214 %R doi:10.3233/BIR-140651 %T Tissue oxygen partial pressure in the tibialis anterior muscle in patients with claudication before, during and after a two-stage treadmill stress test %U https://doi.org/10.3233/BIR-140651 2-3 %X BACKGROUND: The role of the microcirculation in the pathophysiology and symptoms of peripheral arterial obliterative disease (PAOD) has been progressively emphasized during the past decades. Under resting conditions, already, the tissue oxygen partial pressure in the m. tibialis anterior (pO2im) is reduced to about 50% compared to healthy subjects.,METHODS: In the framework of this study the pO2im of patients with PAOD stage II according to Fontaine (n=16) in the m. tibialis anterior was measured under resting conditions and during walking on a treadmill in comparison to healthy subjects (n=10).,RESULTS: Under resting conditions the pO2im only marginally differed between PAOD patients and healthy subjects. But during exercise the pO2im dropped significantly more severely in PAOD patients and a return to baseline values could only be reached when the treadmill was stopped and the patients stood still. The pO2im minima correlated clearly with the clinical symptom of calf pain.,CONCLUSION: The data revealed that the pO2im values were lower in PAOD patients and dropped significantly faster during walking compared to the pO2im values in healthy subjects. The pO2im decrease correlated with the calf pain occurring when the pO2im values approached or fell below 10 mmHg. %0 journal article %@ 0006-355X %A Hardeman, M.,Alexy, T.,Brouwer, B.,Connes, P.,Jung, F.,Kuipers, H.,Baskurt, O.K. %D 2014 %J Biorheology %N 2-3 %P 83-90 %R doi:10.3233/BIR-140655 %T EPO or PlacEPO? Science versus Practical Experience Panel discussion on efficacy of erythropoetin in improving performance %U https://doi.org/10.3233/BIR-140655 2-3 %X Recombinant human erythropoietin (rHuEPO) is an agent commonly used by athletes with the aim to improve performance in endurance sports. However, the scientific community continues to debate the risks, benefits and its mechanism of action when used as a doping agent. This paper provides a brief overview on the pros and cons of rHuEPO use, as discussed by a group of scientist with diverse background, at the 17th Conference of the European Society for Clinical Hemorheology and Microcirculation in Pecs, Hungary. Among multiple topics, panel members challenged the common belief that the increased circulating hemoglobin concentration is the simple key to the improved sporting performance. Rather, hemorheologists developed the concept of optimal hematocrit (Hct), a Hct value that represents the optimal balance between the oxygen transport capacity of blood and blood viscosity. While guideline-directed transfusion therapy is advantageous under pathological conditions, such as severe anemia related to chronic kidney disease, its beneficial effects on endurance in healthy athletes remains questionable. Further studies are warranted in the field evaluating the effects of rHuEPO that are independent of increasing hemoglobin concentration, such as peripheral vasodilation and tissue metabolic changes. %0 journal article %@ 1422-0067 %A Franke, R.-P.,Krueger, A.,Scharnweber, T.,Wenzel, F.,Jung, F. %D 2014 %J International Journal of Molecular Sciences %N 9 %P 16134-16152 %R doi:10.3390/ijms150916134 %T Effects of Radiographic Contrast Media on the Micromorphology of the Junctional Complex of Erythrocytes Visualized by Immunocytology %U https://doi.org/10.3390/ijms150916134 9 %X Effects of radiographic contrast media (RCM) application were demonstrated in vitro and in vivo where the injection of RCM into the A. axillaris of patients with coronary artery disease was followed by a significant and RCM-dependent decrease of erythrocyte velocity in downstream skin capillaries. Another study in pigs revealed that the deceleration of erythrocytes coincided with a significant reduction of the oxygen partial pressure in the myocardium—supplied by the left coronary artery—after the administration of RCM into this artery. Further reports showed RCM dependent alterations of erythrocytes like echinocyte formation and exocytosis, sequestration of actin or band 3 and the buckling of endothelial cells coinciding with a formation of interendothelial fenestrations leading to areas devoid of endothelial cells. Key to morphological alterations of erythrocytes is the membrane cytoskeleton, which is linked to the band 3 in the erythrocyte membrane via the junctional complex. Fundamental observations regarding the cell biological and biochemical aspects of the structure and function of the cell membrane and the membrane cytoskeleton of erythrocytes have been reported. This review focuses on recent results gained, e.g., by advanced confocal laser scanning microscopy of different double-stained structural elements of the erythrocyte membrane cytoskeleton. %0 conference lecture %@ %A Braune, S.,Gross, M.,Walter, M.,Zhou, S.,Dietze, S.,Kratz, K.,Lendlein, A.,Tschoepe, C.,Jung, F. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Platelet adhesion and activation on polymer-based biomaterials - A comparative pilot study of platelets from patients with coronary artery disease and apparently healthy donors %U %X %0 journal article %@ 1386-0291 %A Roch, T.,Schulz, C.,Jung, F.,Ma, N.,Lendlein, A. %D 2014 %J Clinical Hemorheology and Microcirculation %N 2 %P 203-212 %R doi:10.3233/CH-141831 %T Interaction of poly(ether imide) films with early immune mechanisms %U https://doi.org/10.3233/CH-141831 2 %X With the worldwide increase of atherosclerosis, the need for new engineered patient specific implants such as stents or vascular grafts is still emerging. Recently, very smooth poly(ether imide) (PEI) films were, based on their excellent hemocompatibility and compatibility with endothelial cells, suggested as potential biomaterial for cardiovascular applications. In atherosclerosis, immune mechanisms such as complement activation, but also cellular responses such as monocytes and neutrophils activation, can mediate the inflammatory response. Therefore, it is important that the implant material itself does not trigger the inflammatory response. Early immune mechanisms - e.g. macrophage activation, complement induction, generation of reactive oxygen species (ROS), and the secretion of inflammatory cytokines by leukocytes - could potentiate the inflammatory responses, and may thereby alter endothelial cells behaviour or facilitate platelet activation. Therefore, it is important to evaluate the immuno-compatibility of PEI-films. The PEI-films were fabricated from commercially available PEI, which was dissolved in dichloromethane and pulled out on a cleaned, smooth glass surface and subsequently, solvent residues were removed during the drying procedure. Using a murine macrophage reporter cell line possible material bound microbial contaminations and material intrinsic immuno-stimulatory properties were investigated. The macrophages were viable after adhering on the PEI-films and did not show signs of activation, indicating that the used PEI-film was free of microbial contaminations. To determine whether PEI-films induced complement activation, the release of C5a in pooled human plasma was analyzed. The detected C5a levels did not differ between PEI-films and tissue culture plates (TCP), which served as control material. Furthermore, in whole human blood, the generation of ROS as well as the cytokine production were investigated by flow cytometry and by multiplex bead arrays, respectively. The production of IL-6 and TNF-α as well as the generation of ROS by immune cells of the whole blood was not induced upon contact with PEI-films. The immunological evaluation of PEI-films revealed that no substantial activation of the investigated early immune mechanisms occurred. Altogether, this data demonstrate that PEI is immuno-compatible and from that perspective may be a suitable biomaterial for cardiovascular applications. %0 journal article %@ 2050-750X %A Neffe, A.T.,Ruesten-Lange, M.v.,Braune, S.,Luetzow, K.,Roch, T.,Richau, K.,Krueger, A.,Becherer, T.,Thuenemann, A.F.,Jung, F.,Haag, R.,Lendlein, A. %D 2014 %J Journal of Materials Chemistry B %N 23 %P 3626-3635 %R doi:10.1039/C4TB00184B %T Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility %U https://doi.org/10.1039/C4TB00184B 23 %X Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials. %0 conference poster %@ %A Neffe, A.T.,Ruesten-Lange, M.v.,Braune, S.,Luetzow, K.,Roch, T.,Jung, F.,Weinhart, M.,Haag, R.,Lendlein, A. %D 2014 %J Makromolekulares Kolloquium 2014 %N %P %T Polyethers on Porous Polymer Surfaces: Relevant Models to Study Protein Adsorption and Hemocompatibility %U %X %0 conference lecture %@ %A Li, Z.,Wang, W.,Kratz, K.,Xu, X.,Roch, M.,Kurtz, A.,Gossen, M.,jung, F.,Ma, N.,Lendlein, A. %D 2014 %J 6th Forum on New Materials: Symposium Smart Polymers for Biomedical Applications, CIMTEC 2014 %N %P %T Scaffold Roughness Regulates the Endothelial Differentiation of Human Adipose Derived Mesenchymal Stem Cells %U %X %0 conference poster %@ %A Braune, S.,Jung, F.,Lendlein, A. %D 2014 %J Biologisierte Medizintechnik, 28. Treffpunkt Medizintechnik %N %P %T Investigation of in vitro and in vivo hemocompatibility %U %X %0 conference lecture %@ %A Franke, R.P.,Scharnweber, T.,Fuhtmann, R.,Mrowietz, C.,Wenzel, F.,Krueger, A.,Jung, F.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Radiographic contrast media alterate the localization of actin/band4.9 in the membrane cytoskeleton of human erythrocytes %U %X %0 journal article %@ 1386-0291 %A Roch, T.,Akymenko, O.,Krueger, A.,Jung, F.,Ma, N.,Lendlein, A. %D 2014 %J Clinical Hemorheology and Microcirculation %N 1 %P 147-158 %R doi:10.3233/CH-141885 %T Expression pattern analysis and activity determination of matrix metalloproteinase derived from human macrophage subsets %U https://doi.org/10.3233/CH-141885 1 %X The polarization behavior of macrophages determines the clinical outcome after implantation of biomaterials. Formation of classically activated macrophages (CAM) may result in cell fusion to form foreign body giant cells, which induce and support uncontrolled inflammatory responses and can cause undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. The expression of matrix metalloproteinases (MMP) by the different macrophage subsets might play a crucial role for inflammatory and wound healing processes and may subsequently influence the implant integration. Therefore, it is of importance to characterize the MMP expression pattern by the different macrophage subsets. This knowledge could support the design of biomaterials in which specific MMP cleavage sites are incorporated allowing a controlled cell-mediated degradation of the material. However, it needs to be considered that the pure expression levels may not correlate with the enzymatic activity of the MMP, which depends on a variety of different parameters such as additional co-factors. For this reason, the differential MMP expression levels and the overall enzymatic activity of in vitro generated human non-polarized macrophages (M0), CAM, and AAM are analyzed in this study. While MMP-1, MMP-3, and MMP-10 showed the highest expression levels in CAM, MMP-12 was most strongly expressed by AAM. Interestingly, although various MMP were expressed at high levels in CAM, the enzymatic MMP activity was increased in supernatants of AAM cultures. The data presented here illustrate the importance to combine the measurement of MMP expression levels with the analysis of the enzymatic activity. The observed MMP-12 expression in combination with the higher enzymatic activity detected in AAM supernatants might motivate the design of biomaterials, whose structure could be modified by MMP-12 catalyzed reactions leading to interactive polymers. %0 conference lecture (invited) %@ %A Lendlein, A.,Jung, F. %D 2014 %J Biologisierte Medizintechnik, 28. Treffpunkt Medizintechnik %N %P %T Biofunktionale Materialsysteme fuer die Medizintechnik %U %X %0 conference lecture %@ %A Kratz, K.,Jung, F.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Development of shape-memory polymer-based Implants at HZG %U %X %0 conference lecture %@ %A Braune, S.,Dietze, S.,Roch, T.,Krueger, A.,Baudis, S.,Behl, M.,Kratz, K.,Jung, F.,Lendlein, A. %D 2014 %J 6th Forum on New Materials: Symposium Smart Polymers for Biomedical Applications, CIMTEC 2014 %N %P %T Bicompatibility of a Degradable Poly[(L-lactide)-coglycolide] Network %U %X %0 journal article %@ 0376-7388 %A Rangou, S.,Buhr, K.,Filiz, V.,Clodt, J.I.,Lademann, B.,Hahn, J.,Jung, A.,Abetz, V. %D 2014 %J Journal of Membrane Science %N %P 266-275 %R doi:10.1016/j.memsci.2013.10.015 %T Self-organized isoporous membranes with tailored pore sizes %U https://doi.org/10.1016/j.memsci.2013.10.015 %X Membrane formation via the combination of self-assembly and the non-solvent induced phase separation (NIPS) process of diblock copolymers is investigated. Several polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymers with different molecular weights and weight percentages of both blocks are tested under different parameters, leading to membrane surfaces with uniform pores of approximately 20–70 nm diameter. The average pore diameter is proved to be adjustable by changing the total molar mass of the block copolymer. The solution composition is an additional parameter controlling the structure formation. The purpose was to explore the upper and lower limits of the membrane structure formation by varying the molecular weight and the composition of the block copolymer. Scanning electron microscopy (SEM) is used to image the surface morphology and the homogeneity of the pore sizes. Primary results of water flux and retention are presented. %0 conference lecture %@ %A Krueger, A.,Ullm, S.,Gebauer, T.G.,Neffe, A.T.,Pietzsch, J.,Jung, F.,Lendlein, A. %D 2014 %J 33. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Interaction between human umbilical venous endothelial cell and a gelatin-based hydrogel %U %X %0 journal article %@ 1386-0291 %A König, J.,Kohl, B.,Kratz, K.,Jung, F.,Lendlein, A.,Ertel, W.,Schulze-Tanzil, G. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 523-533 %R doi:10.3233/CH-131788 %T Effect of polystyrene and polyether imide cell culture inserts with different roughness on chondrocyte metabolic activity and gene expression profiles of aggrecan and collagen %U https://doi.org/10.3233/CH-131788 4 %X In vitro cultured autologous chondrocytes can be used for implantation to support cartilage repair. For this purpose, a very small number of autologous cells harvested from a biopsy have to be expanded in monolayer culture. Commercially available polymer surfaces lead to chondrocyte dedifferentiation. Hence, the demanding need for optimized polymers and surface topologies supporting chondrocytes' differentiated phenotypes in vitro arises. In this study we explored the effect of tailored cell culture plate inserts prepared from polystyrene (PS) and polyether imide (PEI) exhibiting three different roughness levels (R0, RI, RII) on chondrocyte morphology, metabolism and gene expression profile. As a control, commercially available tissue culture plastic (TCP) dishes were included. Primary porcine articular chondrocytes were seeded on tailored PS and PEI inserts with three different roughness levels. The metabolic activity of the chondrocytes was determined after 24 hours using alamar blue assay. Chondrocyte gene expression profiles (aggrecan, type I and type II collagen) were monitored after 48 hours using Real Time Detection (RTD)-PCR. Chondrocytes cultured on PS and PEI surfaces formed cell clusters after 24 and 48 hours, which was not observed on TCP. The metabolic activity of chondrocytes cultured on PS was lower than of chondrocytes cultured on PEI, but also lower than on TCP. Gene expression analyses revealed an elevated expression of cartilage-specific aggrecan and an impaired expression of both collagen types by chondrocytes on PS and PEI compared with TCP. In summary, PEI is a biocompatible biomaterial suitable for chondrocyte culturing, which can be further chemically functionalized for generating specific surface interactions or covalent binding of biomolecules. %0 journal article %@ 1386-0291 %A Rüder, C.,Sauter, T.,Kratz, K.,Haase, T.,Peter, J.,Jung, F.,Lendlein, A.,Zohlnhöfer, D. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 513-522 %R doi:10.3233/CH-131787 %T Influence of fibre diameter and orientation of electrospun copolyetheresterurethanes on smooth muscle and endothelial cell behaviour %U https://doi.org/10.3233/CH-131787 4 %X Polymers exhibiting cell-selective effects represent an extensive research field with high relevance for biomedical applications e.g. in the cardiovascular field supporting re-endothelialization while suppressing smooth muscle cell overgrowth. Such an endothelial cell-selective effect could be recently demonstrated for a copolyetheresterurethane (PDC) containing biodegradable poly(p-dioxanone) and poly(ε-caprolactone) segments, which selectively enhanced the adhesion of human umbilical vein endothelial cells (HUVEC) while suppressing the attachment of smooth muscle cells (SMC). In this study we investigated the influence of the fibre orientation (random and aligned) and fibre diameter (2 μm and 500 nm) of electrospun PDC scaffolds on the adhesion, proliferation and apoptosis of HUVEC and SMC. Adhesion, viability and proliferation of HUVEC was diminished when the fibre diameter was reduced to a submicron scale, while the orientation of the microfibres did only slightly influence the cellular behaviour. In contrast, a submicron fibre diameter improved SMC viability. In conclusion, PDC scaffolds with micron-sized single fibres could be promising candidate materials for cell-selective stent coatings. %0 journal article %@ 0006-355X %A Jung, F.,Pindur, G.,Ohlmann, P.,Spitzer, G.,Sternitzky, R.,Franke, R.P.,Leithäuser, B.,Wolf, S.,Park, J.-W. %D 2013 %J Biorheology %N 5-6 %P 241-255 %R doi:10.3233/BIR-130645 %T Microcirculation in hypertensive patients %U https://doi.org/10.3233/BIR-130645 5-6 %X Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression. %0 conference lecture %@ %A Xu, X.,Wang, W.,Kratz, K.,Li, Z.,Jung, F.,Ma, N.,Lendlein, A. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Cultivation of rat mesenchymal stem cells on poly(ether imide) surfaces with different microscaled roughness %U %X %0 journal article %@ 1386-0291 %A Hiebl, B.,Hopperdietzel, C.,Hünigen, H.,Dietze, K.,Klein, S.,Schreier, B.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 473-479 %R doi:10.3233/CH-131784 %T Influence of iodine-containing radiographic contrast media on the phenotype of erythrocytes from different laboratory animal species %U https://doi.org/10.3233/CH-131784 4 %X It is well known that clinically relevant concentrations of iodine-containing radiographic contrast media (CM) induce morphological changes in human erythrocytes. However, there are only few reports about CM effects on erythrocytes of animals (e.g. mice, rats, rabbits, and pigs). Thus, two conventional iodine-containing CM (iodixanol, Visipaque™ 320; iomeprol, Iomeprol™ 350) were tested for their effects on the morphology of erythrocytes from these. After venous blood sampling and blood centrifugation, the autologous plasma was supplemented with 40 vol% CM. Then, a defined number of erythrocytes was incubated in this CM-supplemented plasma for 5 min at body temperature (37°C). Subsequently, 10 μL of the cell suspension were transferred to a purified glass slide and the number of discocytes, echinocytes, and acanthocytes was counted within a total number of 100 erythrocytes (40 fold primary magnification, transmitted light mode). Shape changes of the erythrocytes from all animal species strongly depended on the type of CM and compared to the effects which have already been described for human erythrocytes. Incubation in both CM resulted in morphological changes of the erythrocytes. Incubation in a iodixanol/plasma mixture induced the lowest echinocyte or acanthocyte formation. Porcine erythrocytes showed a much more distinct shape change than those of other animal species and humans. These results suggest erythrocytes from mice, rats, and rabbits are a suitable model system for human erythrocytes when CM effects on the cellular shape of erythrocytes have to be tested. The distinct deformation of the pig erythrocytes could be due to differences in the pig erythrocyte membrane or the physical and chemical constitution of pig erythrocytes. %0 journal article %@ 1386-0291 %A Franke, R.P.,Scharnweber, T.,Fuhrmann, R.,Krüger, A.,Wenzel, F.,Mrowietz, C.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 481-490 %R doi:10.3233/CH-131789 %T Distribution of actin of the human erythrocyte membrane cytoskeleton after interaction with radiographic contrast media %U https://doi.org/10.3233/CH-131789 4 %X A type-dependent chemotoxic effect of radiographic contrast media on erythrocytes and endothelial cells was reported several times. While mechanisms of toxicity are still unclear the cellular reactions e.g. echinocyte formation in erythrocytes and the buckling of endothelial cells coincided with deterioration of capillary perfusion (in patients with coronary artery disease) and tissue oxygen tension (in the myocardium of pigs). Whether the shape changes in erythrocytes coincide with changes in the arrangement of actin, the core of the actin-spectrin cytoskeletal network and possible actor in membrane stresses and deformation is not known until now. To get specific informations actin was stained using two different staining methods (antibodies to β-actin staining oligomeric G-actin and polymeric F-actin and Phalloidin-Rhodamin staining polymeric F-actin only). In addition, an advanced version of confocal laser scanning microscopes was used enabling the display of the actin arrangement near substrate surfaces. Blood smears were produced after erythrocyte suspension in autologous plasma or in two different plasma/RCM mixtures. In this study an even homogenous distribution of fine grained globular actin in the normal human erythrocyte could be demonstrated. After suspension of erythrocytes in a plasma/Iodixanol mixture an increased number of membrane protrusions appeared densely filled with intensely stained actin similar to cells suspended in autologous plasma, however, there in less numbers. Suspension in Iopromide, in contrast, induced a complete reorganization of the cytoskeletal actin: the fine grained globular actin distribution disappeared and only few, long and thick actin filaments bundled and possibly polymerized appeared, instead, shown here for the first time. %0 journal article %@ 1386-0291 %A Hiebl, B.,Hopperdietzel, C.,Hünigen, H.,Jung, F.,Scharnagl, N. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 491-499 %R doi:10.3233/CH-131785 %T Influence of a silicon (Si14)-based coating substrate for biomaterials on fibroblast growth and human C5a %U https://doi.org/10.3233/CH-131785 4 %X Despite considerable efforts in biomaterial development there is still a lack on substrates for cardiovascular tissue engineering approaches which allow the establishment of a tight a functional endothelial layer on their surface to provide hemocompatibility. The study aimed to test the biocompatibility of a silicon (Si14)-based coating substrate (Supershine Medicare, Permanon) which was designed to resist temperatures from −40°C up to 300°C and which allows the use of established heat-inducing sterilization techniques respectively. By X-ray photoelectron spectroscopy it could be validated that this substrate is able to establish a 40–50 nm thick layer of silica, oxygen and carbon without including any further elements from the substrate on an exemplary selection of materials (silicone, soda-lime-silica glass, stainless steel). Analysis of the LDH-release, the cell activity/proliferation (MTS assay) and the cell phenotype after growing 3T3 cells with extracts of the coated materials did not indicate any signs of cytotoxicity. Additionally by measuring the C5a release after exposure of the coated materials with human serum it could be demonstrated, that the coating had no impact on the activation of the complement system. These results generally suggest the tested substrate as a promising candidate for the coating of materials which are aimed to be used in cardiovascular tissue engineering approaches. %0 journal article %@ 1386-0291 %A Jung, F.,Leithäuser, B.,Landgraf, H.,Jünger, M.,Franzeck, U.,Pries, A.,Sternitzky, R.,Franke, R.P.,Forconi, S.,Ehrly, A.M. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 411-416 %R doi:10.3233/CH-131778 %T Laser Doppler flux measurement for the assessment of cutaneous microcirculation – critical remarks %U https://doi.org/10.3233/CH-131778 4 %X Back scattered Laser Doppler (LD) signals are composed of two different individual signals. The number of the moving particles and the speed of the particles in the measured tissue volume determine the frequency shift and the band width of the Doppler signal. The dependence of the Laser Doppler flux on the number of scattering particles is highly nonlinear: at very low hematocrit and high speed the axial migration of the cells to the centre of the blood vessels is very strong, so that in these cases – because of the parabolic flow profile - the Doppler flux measurement overestimates the mean real blood flow (up to two- or three-fold). The opposite is the case when the hematocrit is very high, then the blood flow might be underestimated (due to the increased amounts of blood cells near the vessel wall). In addition, a very change in number of moving particles - as can occur during the postprandial phase or during therapy - can change the signal also at a constant cell number. Also, it must be mentioned that the LD signal possibly is not only reflected by moving blood cells in the different skin layers but also by blood cells flowing in tissues below the skin (particularly below atrophied skin areas of older patients) so that in such cases the LD Flux signal reflects not exclusively the skin blood flow. Therefore, LD flux at rest may still be within the normal range even in advanced states of disease, since the scattered light is sampled from a tissue volume which may contain also non-nutritive shunt vessels. This critical analysis of the LD signals of course shall not lead to an overall rejection of the application of laser Doppler systems. Actual progress only can, however, be obtained under the exact consideration of anatomical conditions, technical restrictions and when generalizations are avoided. %0 journal article %@ 1386-0291 %A Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 4 %P 431-431 %R doi:10.3233/CH-131730 %T Book Review %U https://doi.org/10.3233/CH-131730 4 %X %0 journal article %@ 1616-5187 %A Neffe, A.T.,Von Ruesten-Lange, M.,Braune, S.,Luetzow, K.,Roch, T.,Richau, K.,Jung, F.,Lendlein, A. %D 2013 %J Macromolecular Bioscience %N 12 %P 1720-1729 %R doi:10.1002/mabi.201300309 %T Poly(ethylene glycol) Grafting to Poly(ether imide) Membranes: Influence on Protein Adsorption and Thrombocyte Adhesion %U https://doi.org/10.1002/mabi.201300309 12 %X The chain length and end groups of linear PEG grafted on smooth surfaces is known to influence protein adsorption and thrombocyte adhesion. Here, it is explored whether established structure function relationships can be transferred to application relevant, rough surfaces. Functionalization of poly(ether imide) (PEI) membranes by grafting with monoamino PEG of different chain lengths (Mn = 1 kDa or 10 kDa) and end groups (methoxy or hydroxyl) is proven by spectroscopy, changes of surface hydrophilicity, and surface shielding effects. The surface functionalization does lead to reduction of adsorption of BSA, but not of fibrinogen. The thrombocyte adhesion is increased compared to untreated PEI surfaces. Conclusively, rough instead of smooth polymer or gold surfaces should be investigated as relevant models. %0 doctoral thesis %@ %A Jung, A. %D 2013 %J %N %P %T Synthese von Blockcopolymeren zur Darstellung integral asymmetrischer Membranen (Dissertation) %U %X %0 journal article %@ 1386-0291 %A Roch, T.,Kratz, K.,Ma, N.,Jung, F.,Lendlein, A. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1 %P 157-168 %R doi:10.3233/CH-131699 %T The influence of polystyrene and poly(ether imide) inserts with different roughness, on the activation of dendritic cells %U https://doi.org/10.3233/CH-131699 1 %X Dendritic cells (DC) have a pivotal role during inflammation. DC efficiently present antigens to T cells and shape the subsequent immune response by the secretion of pro- or anti-inflammatory cytokines and by the expression of co-stimulatory molecules. They respond to “danger signals” such as microbial products or fragments from necrotic cells or tissues, but were also described to be reactive towards biomaterials. However, how mechanical and physical properties of the subjacent substrate influences the DC activation is currently poorly understood. In this study micro patterned inserts prepared from polystyrene (PS) as well as from poly (ether imide) (PEI) with three different roughness levels of i) Rq = 0.29 μm (PS) and 0.23 μm (PEI); ii) Rq = 3.47 μm (PS) and 3.92 μm (PEI); and iii) Rq = 22.16 μm (PS) and 22.65 μm (PEI) were analyzed for their capacity to influence the activation of human monocytes derived DC. Since the DC were directly cultured in the inserts, the effects of the testing material alone could be investigated and influences from additional culture dish material could be excluded. The viability, the expression of the DC activation markers, and their cytokine/chemokine secretion were determined after the incubation with the different inserts in vitro. Both the PS and the PEI inserts did not influence the survival of the DC and their expression of co-stimulatory molecules. The expression of inflammatory cytokines was not altered by the PEI and PS inserts. However, the secretion of chemokines such as CCL2, CCL3, and CCL4 was influenced by the different roughness levels, indicating that material roughness has the capacity to modulate the DC phenotype. The data presented here will help to understand the interaction of DC with structured polymer surfaces. Biomaterial-induced immuno-modulatory effects mediated by DC may promote tissue regeneration or could potentially reduce inflammation caused by the implant material. %0 conference lecture (invited) %@ %A Jung, F. %D 2013 %J Innovative Materialien fuer die Medizintechnik, 59. DECHEMA-Kolloquium %N %P %T Polymere fuer die Biomedizin %U %X %0 conference lecture %@ %A Wischke, C.,Neffe, A.T.,Ruesten-Lange, M.v.,Braune, S.,Luetzow, K.,Roch, T.,Richau, K.,Jung, F.,Lendlein, A. %D 2013 %J 12th International Conference on Polymers for Advanced Technologies, PAT 2013 %N %P %T The Suitability of Polyethers to Reduce Protein Adsorption and to Improve Hemocompatibility %U %X %0 conference lecture %@ %A Wang, W.,Kratz, K.,Xu, X.,Li, Z.,Jung, F.,Ma, N.,Lendlein, A. %D 2013 %J 17th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2013 %N %P %T Interaction of human mesenchymal stem cells with soft hydrophobic poly(n-butyl acrylate) networks with elastic moduli comparable to arteries %U %X %0 conference poster %@ %A Krueger, A.,Scharnagl, N.,Trescher, K.,Zierke, M.,kratz, K.,Behl, M.,Jung, F.,Lendlein, A. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Behaviour of fibroblasts on water born acrylonitrile based copolymers with varying hydrophilicities %U %X %0 conference lecture %@ %A Ma, N.,Luetzow, C.,Kratz, K.,Furlani, D.,Li, W.,Wang, W.,Pittermann, E.,Neffe, A.T.,Sauter, T.,Jung, F.,Lendlein, A. %D 2013 %J 17th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2013 %N %P %T A three-dimensional stem cell culture system by polyurethane scaffold material %U %X %0 conference lecture %@ %A Schulz, C.,Ruesten-Lange, M.v.,Krueger, A.,Lendlein, A.,Jung, F. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Adherence and shear-resistancy of primary human endothelial cells on smooth poly(ether imide) films %U %X %0 conference poster %@ %A Dietze, S.,Braune, S.,Krueger, A.,Baudis, S.,Behl, M.,Kratz, K.,Jung, F.,Lendlein, A. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Hemocompatibility of degradable poly[(rac-lactide)-co-glycolide] polymer network %U %X %0 journal article %@ 0168-1656 %A Trescher, K.,Roch, T.,Cui, J.,Kratz, K.,Lendlein, A.,Jung, F. %D 2013 %J Journal of Biotechnology %N 1-2 %P 58-64 %R doi:10.1016/j.jbiotec.2013.04.012 %T Test system for evaluating the influence of polymer properties on primary human keratinocytes and fibroblasts in mono- and coculture %U https://doi.org/10.1016/j.jbiotec.2013.04.012 1-2 %X Interactions of cells with polymer-based biomaterials are influenced by properties of the substrate. Polymers, which are able to induce cell specific effects, gain increasing importance for biotechnology and regenerative therapies. A test system was developed, which allows studying primary human keratinocytes and fibroblasts in mono- and cocultures to analyze and operate the effect of polymer properties. This system offers to identify polymers for keratinocyte cultivation or wound dressings, since adherence, viability and functionality can be analyzed. Especially the coculture system enables the characterization of potential cell specific effects of polymer-based biomaterials. To establish a coculture test system, it is challenging to find a suitable culture medium, to identify initial seeding densities for comparable cell growth and to develop methods to distinguish and characterize both cell types.,Poly(n-butyl acrylate) networks (cPnBAs) as model biomaterials were used to demonstrate the applicability of our newly developed coculture screening system for differential cell growth. The apparent Young's modulus of the cPnBAs differentially regulated fibroblasts and keratinocytes. Particularly, cPnBA73 with an apparent Young's modulus of 930 ± 140 kPa measured in phosphate buffered saline (PBS) solution at ambient temperature seemed to have favoring properties for keratinocyte adhesion, while fibroblast adhesion was not affected. For keratinocytes the concentration of some pro-inflammatory cytokines was lower on cPnBA73 and a decreased deposition of collagen, elastin and fibronectin was observed in the coculture. %0 journal article %@ 0939-6411 %A Wischke, C.,Krueger, A.,Roch, T.,Pierce, B.F.,Li, W.,Jung, F.,Lendlein, A. %D 2013 %J European Journal of Pharmaceutics and Biopharmaceutics %N 2 %P 288-296 %R doi:10.1016/j.ejpb.2013.01.025 %T Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio %U https://doi.org/10.1016/j.ejpb.2013.01.025 2 %X Endothelial cells lining the lumen of blood vessels serve as a physiological barrier controlling nanoparticle movement from the vasculature into the tissue. For exploring the effect of polymer hydrophilicity on nanoparticle interactions with human umbilical vein endothelial cells (HUVECs) in vitro, a series of monomodal poly[acrylonitrile-co-(N-vinylpyrrolidone)] model nanoparticles with increasing hydrophilicity as related to their increasing content (0–30 mol.%) of N-vinylpyrrolidone (NVP) were synthesized by miniemulsion polymerization. Nanoparticles with a low NVP content were rapidly endocytized into all cells independent from the particle dose with toxic effects only observed at high particle concentrations, while only 10–30% of the cells incorporated particles with ⩾20 mol.% NVP. Since pathologies are often related to inflammation, an inflammatory HUVEC culture condition with IL-1β stimulation has been introduced and suggested to be widely applied for studying nanocarriers, since cellular uptake in this assay was clearly increased for NVP contents ⩾20 mol.%. Importantly, the secretion of functional biological mediators by HUVECs was not relevantly influenced by the nanoparticles for both homeostatic and inflammatory conditions. These findings may motivate concepts for nanocarriers specifically targeted to pathologic regions. Additionally, rapidly endocytized Rhodamin B loaded particles with low NVP content may be explored for cell labeling and tracking. %0 conference lecture (invited) %@ %A Abetz, V.,Rangou, S.,Filiz, V.,Abetz, C.,Buhr, K.,Clodt, J.,Hahn, J.,Jung, A. %D 2013 %J German Korean Polymer Symposium 2013 %N %P %T Integral Asymmetrc Block Copolymer Membranes: Formation, Functionalization, and Stumili-Responsiveness %U %X %0 conference lecture %@ %A Krueger, A.,Mayer, A.,Roch, T.,Schulz, C.,Jung, F.,Lendlein, A. %D 2013 %J 17th Conference of the European Society for Clinical Hemorheology and Microcirculation, ESCHM 2013 %N %P %T Angiogenically stimulated intermediate monocytes maintain their proangiogenic and non-inflammatory phenotype in long time co-cultures with HUVEC %U %X %0 editorial %@ 1386-0291 %A Jung, F.,Niimi, H.,Forconi, S.,Stoltz, J.F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 1-2 %R doi:10.3233/CH-2012-1570 %T Editorial: 31 Years of Clinical Hemorheology and Microcirculation %U https://doi.org/10.3233/CH-2012-1570 1-2 %X No abstract %0 conference lecture %@ %A Krueger, A.,Trescher, K.,Scharnagl, N.,Kratz, K.,Roch, T.,Lendlein, A.,Jung, F. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %R doi:10.1007/s00382-011-1220-0 %T Adherence and viability of primary human dermal keratinocytes and primary human dermal fibroblasts on acrylonitrile-based copolymers with systematic variations of positively and negatively charged functional groups %U https://doi.org/10.1007/s00382-011-1220-0 %X %0 journal article %@ 1022-1336 %A Jung, A.,Filiz, V.,Rangou, S.,Buhr, K.,Merten, P.,Hahn, J.,Clodt, J.,Abetz, C.,Abetz, V. %D 2013 %J Macromolecular Rapid Communications %N 7 %P 610-615 %R doi:10.1002/marc.201200770 %T Formation of Integral Asymmetric Membranes of AB Diblock and ABC Triblock Copolymers by Phase Inversion %U https://doi.org/10.1002/marc.201200770 7 %X The formation of integral asymmetric membranes from ABC triblock terpolymers by non-solvent-induced phase separation is shown. They are compared with the AB diblock copolymer precursors. Triblock terpolymers of polystyrene-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) (PS-b-P2VP-b-PEO) with two compositions are investigated. The third block supports the formation of a membrane in a case, where the corresponding diblock copolymer does not form a good membrane. In addition, the hydrophilicity is increased by the third block and due to the hydroxyl group the possibility of post-functionalization is given. The morphologies are imaged by scanning electron microscopy. The influence of the PEO on the membrane properties is analyzed by water flux, retention, and dynamic contact angle measurements. %0 journal article %@ 1752-0894 %A Ahmed, M.,Anchukaitis, K.J.,Asrat, A.,Borgaonkar, H.P.,Braida, M.,Buckley, B.M.,Buentgen, U.,Chase, B.M.,Christie, D.A.,Cook, E.R.,Curran, M.A.J.,Diaz, H.F.,Esper, J.,Fan, Z.-X.,Gaire, N.P.,Ge, Q.,Gergis, J.,Gonzalez-Rouco, J.F.,Goosse, H.,Grab, S.W.,Graham, N.,Graham, R.,Grosjean, M.,Hanhijaervi, S.T.,Kaufman, D.S.,Kiefer, T.,Kimura, K.,Korhola, A.A.,Krusic, P.J.,Lara, A.,Lezine, A.-M.,Ljungqvist, F.C.,Lorrey, A.M.,Luterbacher, J.,Masson-Delmotte, V.,McCarroll, D.,McConnell, J.R.,McKay, N.P.,Morales, M.S.,Moy, A.D.,Mulvaney, R. %A Mundo, I.A.,Nakatsuka, T.,Nash,D.J.,Neukom, R.,Nicholson, S.E.,Oerter, H.,Palmer, J.G.,Phipps, S.J.,Prieto, M.R.,Rivera, A.,Sano, M.,Severi, M.,Shanahan, T.M.,Shao, X.,Shi, F.,Sigl, M.,Smerdon, J.E.,Solomina, O.N.,Steig, E.J.,Stenni, B.,Thamban, M.,Trouet, V.,Turney, C.S.M.,Umer, M.,Ommen, T. van,Verschuren, D.,Viau, A.E.,Villalba, R.,Vinther, B.M.,Gunten, L.v.,Wagner, S.,Wahl, E.R.,Wanner, H.,Werner, J.P.,White, J.W.C.,Yasue, K.,Zorita, E. %D 2013 %J Nature Geoscience %N 5 %P 339-346 %R doi:10.1038/NGEO1797 %T Continental-scale temperature variability during the past two millennia %U https://doi.org/10.1038/NGEO1797 5 %X Past global climate changes had strong regional expression. To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia. The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century. At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them. There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century. The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions. Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years. %0 journal article %@ 1616-301X %A Clodt, J.I.,Filiz, V.,Rangou, S.,Buhr, K.,Abetz, C.,Hoeche, D.,Hahn, D.,Jung, A.,Abetz, V. %D 2013 %J Advanced Functional Materials %N 6 %P 731-738 %R doi:10.1002/adfm.201202015 %T Double Stimuli-Responsive Isoporous Membranes via Post-Modification of pH-Sensitive Self-Assembled Diblock Copolymer Membranes %U https://doi.org/10.1002/adfm.201202015 6 %X Double stimuli-responsive membranes are prepared by modification of pH-sensitive integral asymmetric polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymer membranes with temperature-responsive poly(N-isopropylacrylamide) (pNIPAM) by a surface linking reaction. PS-b-P4VP membranes are first functionalized with a mild mussel-inspired polydopamine coating and then reacted via Michael addition with an amine-terminated pNIPAM-NH2 under slightly basic conditions. The membranes are thoroughly characterized by nuclear magnetic resonance (1H-NMR), Fourier transform infrared spectroscopy and X-ray-induced photoelectron spectroscopy. Additionally dynamic contact angle measurements are performed comparing the sinking rate of water droplets at different temperatures. The pH- and thermo-double sensitivities of the modified membranes are proven by determining the water flux under different temperature and pH conditions. %0 journal article %@ 0887-6266 %A Hahn, J.,Filiz, V.,Rangou, S.,Clodt, J.,Jung, A.,Buhr, K.,Abetz, C.,Abetz, V. %D 2013 %J Journal of Polymer Science B %N 4 %P 281-290 %R doi:10.1002/polb.23209 %T Structure formation of integral-asymmetric membranes of polystyrene-block-Poly(ethylene oxide) %U https://doi.org/10.1002/polb.23209 4 %X For the first time the combination of solution casting and solvent–nonsolvent exchange (phase inversion) has been applied to generate asymmetric membranes with highly ordered hexagonally packed cylinders with perpendicular orientation composed of polystyrene-block-poly(ethylene oxide). The influence of parameters like solvent composition and evaporation time on the membrane formation is presented. The development is based on a study of the solution behavior by dynamic light scattering and the precipitation behavior of the cylinder forming diblock copolymer by turbidity measurements from different solvent and nonsolvent systems. The water flux properties, as an important membrane characteristic, show a time dependent behavior, due to swelling of the polyethylene oxide blocks. The morphologies of the membranes are imaged by scanning electron microscopy. %0 journal article %@ 1022-1336 %A Clodt, J.,Rangou, S.,Schroeder, A.,Buhr, K.,Hahn, J.,Jung, A.,Filiz, V.,Abetz, V. %D 2013 %J Macromolecular Rapid Communications %N 2 %P 190-194 %R doi:10.1002/marc.201200680 %T Carbohydrates as additives for the formation of isoporous PS-b-P4VP diblock copolymer membranes %U https://doi.org/10.1002/marc.201200680 2 %X Highly porous polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymer membranes are prepared using carbohydrates as additives. Therefore α-cyclodextrine, α-(D)-glucose, and saccharose (cane sugar) are tested for the membrane formation of three different PS-b-P4VP polymers. The addition of the carbohydrates leads to an increasing viscosity of the membrane solutions due to hydrogen bonding between hydroxyl groups of the carbohydrates and pyridine units of the block copolymer. In all cases, the membranes made from solution with carbohydrates have higher porosity, an improved narrow pore distribution on the surface and a higher water flux as membranes made without carbohydrates with the same polymer, solvent ratio, and polymer concentration. %0 journal article %@ 1934-8630 %A Braune, S.,Grunze, M.,Straub, A.,Jung, F. %D 2013 %J Biointerphases %N 1 %P 33 %R doi:10.1186/1559-4106-8-33 %T Are there sufficient standards for the in vitro hemocompatibility testing of biomaterials? %U https://doi.org/10.1186/1559-4106-8-33 1 %X No abstract %0 journal article %@ 1438-7492 %A Hahn, J.,Filiz, V.,Rangou, S.,Lademann, B.,Buhr, K.,Clodt, J.I.,Jung, A.,Abetz, C.,Abetz, V. %D 2013 %J Macromolecular Materials and Engineering %N 12 %P 1315-1321 %R doi:10.1002/mame.201300012 %T PtBS-b-P4VP and PTMSS-b-P4VP Isoporous Integral-Asymmetric Membranes with High Thermal and Chemical Stability %U https://doi.org/10.1002/mame.201300012 12 %X Isoporous integral-asymmetric membranes of tailor-made poly(tert-butylstyrene)- and poly(4-trimethylsilylstyrene)-block-poly(4-vinylpyridine) diblock copolymers are reported here for the first time. The membrane development involved the optimization of the production process—which is a combination of block copolymer self-assembly and the non-solvent induced phase inversion process. The membranes showed an improved thermal and chemical stability compared to previously reported polystyrene-block-poly(4-vinylpyridine) membranes, thus the number of potential application areas for such type of isoporous membranes is increased. %0 journal article %@ 1386-0291 %A Franke, R.P.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 143-153 %R doi:10.3233/CH-2012-1582 %T Pathophysiology of the contrast media-induced nephropathy (CIN) in patients undergoing coronary interventions %U https://doi.org/10.3233/CH-2012-1582 1-2 %X Contrast media-induced nephropathy (CIN) is a known complication of intra-arterial application of radiographic contrast media (RCM) and is associated with both short- and long-term outcomes. The development of CIN is not easy to diagnose due to a lack of a uniform definition of CIN. CIN was reported in 4 to 20% of patients after intra-arterial RCM administration during coronary angiography. An all-cause mortality rate of CIN patients amounted to 9% compared with 2% among patients not developing CIN. Pre-existing chronic renal insufficiency, especially, was described as important factor predisposing for CIN, but there was recent clinical evidence that CIN may occur also in low risk ambulatory patients, probably depending on the type of RCM used. Strongly depending on the type of RCM administered there were marked differences in the morphological changes of erythrocytes as well as endothelial cells coinciding in some cases with microcirculatory disorders in patients as well as in animal models. Iodixanol brought about the least cellular and microcirculatory effects while Iopromide induced the strongest disturbances in capillary perfusion and myocardial oxygen tension. It is unclear, however, whether this favours the development of CIN. %0 journal article %@ 1386-0291 %A Xu, X.,Kratz, K.,Wang, W.,Li, Z.,Roch, T.,Jung, F.,Lendlein, A.,Ma, N. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1 %P 143-156 %R doi:10.3233/CH-131698 %T Cultivation and spontaneous differentiation of rat bone marrow-derived mesenchymal stem cells on polymeric surfaces %U https://doi.org/10.3233/CH-131698 1 %X Accumulating evidence demonstrated many physical and chemical cues from the local microenvironment could influence mesenchymal stem cells (MSCs) maintenance and differentiation. In this study, we systematically investigated the interaction of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and polymeric substrates. Adhesion, proliferative capacity, cytoskeleton alteration, cytotoxicity, apoptosis, senescence, and adipogenesis potential of rBMSCs were determined on these polymeric inserts prepared from polyetherurethane (PEU) and poly(ether imide) (PEI). Inserts for culture plates were applied to ensure that the rBMSCs were solely in contact to the tested material. The explored inserts exhibited advancing contact angles of 84° (PEU) and 93° (PEI). Finally, the micromechanical properties determined by atomic force microscopy (AFM) indentation varied in the range from 6 GPa (PEU) to 13 GPa (PEI). We found that both PEU and PEI showed a good cell compatibility to rBMSCs. rBMSCs could adherent on both polymeric surfaces with the similar adhesion ratio and subsequent division rate. However, cells cultured on PEU exhibited higher apoptosis level and senescence ratio, which resulted in lower cell density (22061 ± 3000/cm2) compared to that on PEI (68395 ± 8000/cm2) after 20 days cultivation. Morphological differences of rBMSCs were detected after 5 days cultivation. Cells on PEU exhibited flat and enlarged shape with rearranged filamentous actin (F-actin) cytoskeleton, while cells on PEI and tissue culture plate (TCP) had similar spindle-shape morphology and oriented F-actin. After 20 days, lipid droplets were spontaneously formed in rBMSCs on PEU and PEI but not on TCP. Both PEU and PEI might trigger rBMSCs towards spontaneous adipogenic commitment, whereas PEI provided better cell compatibility on rBMSCs apoptosis, senescence and proliferation. %0 conference lecture %@ %A Franke, R.-P.,Scharnweber, T.,Fuhrmann, R.,Mrowietz, C.,Jung, F. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Einfluss von Roentgenkontrastmittel (Iodixanol, Iopromide) auf das Spektrin/Aktin-Netzwerk des Membranzytoskeletts von Erythrozyten %U %X %0 conference lecture %@ %A Braune, S.,Alagoez, G.,Zhou, S.,Roch, T.,Kratz, K.,Lendlein, A.,Jung, F. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Static in vitro hemocompatibility testing of hydrophobic poly(n-butyl acrylate) networks with high crosslink densities %U %X %0 conference lecture %@ %A Ma, N.,Xu, X.,Kratz, K.,Wang, W.,Li, Z.,Jung, F.,Lendlein, A. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T The Influence of Geometrically Patterned Polymer Surfaces on the Development of Human Mesenchymal Stem Cells %U %X %0 conference lecture %@ %A Rueder, C.,Haase, T.,Sauter, T.,Kratz, K.,Peter, J.,Jung, F.,Lendlein, A.,Zohlnhoefer, D. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T In Vivo Assessment of Poly(ether imide) (PEI) Electrospun Scaffold and Film by Subcutaneous Implantation in Mice %U %X %0 conference lecture %@ %A Rueder, C.,Sauter, T.,Kratz, K.,Haase, T.,Peter, J.,Jung, F.,Lendlein, A.,Zohlnhoefer, D. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Influence of fiber diameter and orientation of electrospun copolyetheresterurethanes on smooth muscle and endothelial cell behaviour %U %X %0 conference lecture %@ %A Roch, T.,Schulz, C.,Jung, F.,Ma, N.,Lendlein, A. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Interaction of poly(ether imide) films with early immune mechanisms %U %X %0 conference lecture %@ %A Jung, F.,Mrowietz, C.,Schulz, C.,Blaschke, F.,mueller, D.,Lendlein, A.,Schunk, W.-H. %D 2013 %J 32. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Wirkung von Zytochrom P-450-abhaengigen Eikosanoid-Analoga auf die Ristozetin-induzierte Thrombozytenaggregation %U %X %0 journal article %@ 0167-5273 %A Leithaeuser, B.,Park, J.-W.,Hill, P.,Lam, Y.-Y.,Jung, F. %D 2013 %J International Journal of Cardiology %N 1 %P 582-583 %R doi:10.1016/j.ijcard.2013.01.254 %T Magnetocardiography in patients with acute chest pain and bundle branch block %U https://doi.org/10.1016/j.ijcard.2013.01.254 1 %X No abstract %0 journal article %@ 1386-0291 %A Franke, R.P.,Scharnweber, T.,Fuhrmann, R.,Mrowietz, C.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 3 %P 273-285 %R doi:10.3233/CH-131733 %T Effect of radiographic contrast media (Iodixanol, Iopromide) on the spectrin/actin-network of the membranous cytoskeleton of erythrocytes %U https://doi.org/10.3233/CH-131733 3 %X Red blood cells demonstrate a unique ability for repeated large deformation. Under the influence of a variety of agents, shapes other than the discocyte – e.g. stomatocytes or echinocytes - can be observed. Some radiographic agents induce shape changes from discocytic to echinocytic cells. Especially the echinocyte formation is associated with a rigidification of the cells bearing the risk of a hindered capillary passage of the echinocytes. The mechanisms leading to the formation of echinocytes are not well understood assuming that the membrane cytoskeleton is a key player. That is why this examination was focused on the participation of components of the membrane cytoskeleton in the formation of echinocytes and the protrusions accompanying the formation of echinocytes. Two radiographic contrast media approved for intra-arterial application were used to study echinocyte formation (Iodixanol320; Iopromide370). In the in vitro study serious changes in the membrane cytoskeleton were only found in those erythrocytes incubated in plasma supplemented with Iopromide370 (30%v/v). The shape of the spectrin net was completely altered; from the more homogeneous distribution - typical of cells in autologous plasma and also of cells in plasma supplemented with Iodixanol320 – to a distribution of spectrin concentrated in the membrane-near regions with the appearance of spectrin-actin co-localization. Co-localized spectrin with actin was also found around the membranous roots of protrusions which resemble exocytotic processes. In central parts of the cells there was a pronounced dissociation of spectrin and actin; green coloured condensed spectrin bundles originating from the cell membrane reached up to the root of the protrusions. Separate from this there were also fine long actin fibres passing through the whole cell. The incubation of erythrocytes in plasma supplemented with Iopromide370 induced rounded bubble-like protrusions from the cell membrane containing almost completely long bundles of actin fibres. The examination confirmed earlier studies showing that some radiographic contrast media are able to induce echinocyte formation. Furthermore, subcellular mechanisms were revealed explaining the different effects of Iodixanol in comparison to Iopromide. %0 journal article %@ 1386-0291 %A Krueger, A.,Mrowietz, C.,Lendlein, A.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1 %P 111-120 %R doi:10.3233/CH-131695 %T Interaction of human umbilical vein endothelial cells (HUVEC) with platelets in vitro: Influence of platelet concentration and reactivity %U https://doi.org/10.3233/CH-131695 1 %X Endothelialisation of polymer-based cardiovascular implants is one strategy to render biomaterials hemocompatible. The evaluation of the functionality and the confluence of an endothelial cell (EC) monolayer in vitro is therefore of crucial importance, because a non-functional or non-confluent EC monolayer can contribute to the failure of vascular grafts. Moreover, the comparison of different potential biomaterials regarding their ability to induce the formation of a functional confluent EC monolayer is of great value. Most of the currently reported in vitro studies focus on direct or indirect markers of EC behaviour. However, these studies still lack the final proof that the EC monolayer, which can be developed on polymers is confluent and functional. In this study, we investigated the suitability of an in vitro co-culture of human umbilical vein endothelial cells (HUVEC) with platelets to predict the functionality of an EC monolayer. The interaction of platelets with HUVEC was evaluated depending on the concentration of the platelets in the added plasma and of the reactivity of the platelets to pharmacological stimuli. For this purpose, HUVEC were seeded in a 24 well plate. After three days of cultivation, platelets were added to the HUVEC cell culture medium to final concentrations of 200, 2,000 or 20,000 platelets/μl (n = 7 each). The platelets were processed immediately after blood collection and added to the HUVEC culture after a 30 minutes resting period. As a first control, an EC monolayer just cultured with EC medium was used. As a second control EC supplemented with plasma without platelets were applied. The HUVEC monolayer was investigated microscopically after 1 hour of platelet exposition. The addition of thrombocytes to EC affected the EC adherence dependent on the initial cell seeding number of HUVEC, the platelet concentration and also on the reactivity of platelets added. In both controls no significant EC detachment was detected. The results demonstrated a significant influence of platelet concentration and reactivity on the adherence of EC in a static model. %0 journal article %@ 1386-0291 %A Krueger, A.,Goers, J.,Zaupa, A.,Loewenberg, C.,Pierce, B.F.,Wischke, C.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1 %P 133-142 %R doi:10.3233/CH-131697 %T Influence of physically crosslinked gelatins on the vasculature in the avian chorioallantoic membrane %U https://doi.org/10.3233/CH-131697 1 %X Gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) form physically crosslinked hydrogels, due to the interactions between the introduced aromatic moieties and gelatin triple helices, whose extent depends on the thermal treatment of the material. The G-modulus of these hydrogels can be tailored to the range of the natural extracellular matrix by adjusting the degree of crosslinking. While these gelatin-based materials have been shown to be not angiogenic, the aim of the study was to evaluate whether these biomaterials influence the regulation of blood vessels when positioned on the chorionallantoic membrane (CAM) of fertilized eggs. The results clearly indicate that the DAT-functionalized gelatin led to an increase of the diameter of the blood vessels in the CAM, which at the same time is probably associated with an increased blood flow in these CAM vessels. The vessel diameters of the four groups (DAT-functionalized gelatin, DATT-functionalized gelatin, plain gelatin, control group without gelatin, each n = 10) differed significantly (p < 0.0001). Vessels in the CAM exposed to the DAT-functionalized gelatin showed with 36.4 μm ± 3.4 μm the largest mean diameters compared to the mean diameters of the samples exposed to DATT gelatin (16.0 μm ± 0.8 μm; p < 0.05) and the plain gelatin (21.2 μm ± 1.0 μm; p < 0.05), which both did not differ significantly from the vessels of the control group. The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (one hour up to several days). %0 journal article %@ 1386-0291 %A Jung, F.,Braune, S.,Lendlein, A. %D 2013 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 97-115 %R doi:10.3233/CH-2012-1579 %T Haemocompatibility testing of biomaterials using human platelets %U https://doi.org/10.3233/CH-2012-1579 1-2 %X Cardiovascular implants are increasingly important in regenerative medicine. To improve the safety and function of blood-contacting implants a major need exists for new polymer-based biomaterials that avoid adverse reactions, particularly thrombotic events. This review is aimed to summarize the multi-stepped and interlinked processes leading to a thrombus growth on body foreign surfaces: protein adsorption, platelet adhesion accompanied by activation and spreading and the release of substances of various organelles activating other neighboured platelets (and the plasmatic coagulation) leading to the formation of a plug of platelets and, finally, to a thrombus. %0 journal article %@ 1386-0291 %A Braune, S.,Ruesten-Lange, M.v.,Mrowietz, C.,Luetzow, K.,Roch, T.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2013 %J Clinical Hemorheology and Microcirculation %N 3 %P 235-248 %R doi:10.3233/CH-131729 %T Dynamic in vitro hemocompatibility testing of poly(ether imide) membranes functionalized with linear, methylated oligoglycerol and oligo(ethylene glycol) %U https://doi.org/10.3233/CH-131729 3 %X Linear, side-chain methylated oligoglycerols (OGMe) were recently reported as potential surface passivating molecules for improving the protein resistance of cardiovascular application relevant poly(ether imide) (PEI) membranes. A previously reported in vitro screening under static test conditions allowed an end-point evaluation of the adhesion and activation of adherent thrombocytes performed on the material surfaces and revealed similar levels of thrombogenicity on PEI membranes, functionalized with OGMe and oligo(ethylene glycol) (OEG) of similar molecular weight (Mn = 1,300 g·mol−1 - 1,800 g·mol−1). In the present study, we investigated the hemocompatibility of these materials in a dynamic closed loop system, in order to study time-dependent thrombocyte material interactions also of the circulating thrombocytes by mimicking in vivo relevant flow conditions in a dynamic test system with multiple material contacts. Activation and aggregation of circulating thrombocytes as well as complement activation and plasmatic coagulation were evaluated after 40 circulations of thrombocyte rich plasma in the closed loop system. The results of the dynamic tests revealed no differences between the OGMe and OEG functionalized PEI membranes. Furthermore, no differences were observed between the latter and a PEI membrane treated under the conditions of functionalization at pH 11 (PEI-pH11) without an oligoether being present. Blood plasma protein adsorption, as well as activation, and adherence of circulating thrombocytes occurred in a comparable, but minor manner on all investigated PEI membranes. From this we conclude that the OGMe and OEG surface functionalization did not lead to an improvement of the already good hemocompatibility of the PEI-pH11 membrane. %0 conference lecture %@ %A Goers, J.,Krueger, A.,Gebauer, T.,Pierce, B.F.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2012 %J 14th International Congress of Biorheology, 7th International Conference on Clinical Hemorheology %N %P %T Influence of chemically crosslinked gelatin on the vasculature in the avian chorioallantoic membrane %U %X %0 conference lecture %@ %A Jung, F. %D 2012 %J Querschnittsverbund Technologie und Medizin: STENT Workshop %N %P %T Performance und Anforderungen von Stents aus Sicht des Ingenieurs %U %X %0 journal article %@ 1742-7061 %A Mayer, A.,Roch, T.,Kratz, K.,Lendlein, A.,Jung, F. %D 2012 %J Acta Biomaterialia %N 12 %P 4253-4259 %R doi:10.1016/j.actbio.2012.08.011 %T Pro-angiogenic CD14++ CD16+ CD163+ monocytes accelerate the in vitro endothelialization of soft hydrophobic poly(n-butyl acrylate) networks %U https://doi.org/10.1016/j.actbio.2012.08.011 12 %X As the majority of the polymers used as cardiovascular grafts so far do not match the elasticity of human arteries (100–1000 kPa) and the required endothelialization, a multifunctional material approach is needed to allow the adjustment of the mechanical properties while at the same time exhibiting a haemocompatible surface. Recently soft poly(n-butyl acrylate) networks (cPnBA) with adjustable mechanical properties were introduced as candidate materials with a surface that can be endothelialized. In this study, angiogenically stimulated intermediate CD163+ monocytes/macrophages (aMO2) were utilized as a cellular cytokine release system to realize the functional endothelialization of the hydrophobic cPnBA surface. We investigated the influence of co-cultured aMO2 on the morphology, density and cytokine secretion of human umbilical venous endothelial cells (HUVEC) seeded on cPnBA with an elastic modulus of around 250 kPa (cPnBA0250). A functional confluent HUVEC monolayer could be developed in the co-culture within 3 days. In contrast, the HUVEC in the monoculture exhibited stress fibres, broadened marginal filament bands and significantly more and larger cell-free areas in the monolayer, indicating incomplete cell–substrate binding. Remarkably, a functional confluent monolayer formation could only be achieved in co-cultures; it did not develop with the sole supplementation of recombinant VEGF-A165 to the HUVEC monocultures (unpublished data). The study demonstrated the multifunctional potential of cPnBA in combination with aMO2 as a cellular cytokine release system, adapting their secretion to the demand of HUVEC. In this way, a functional confluent monolayer could be generated within 3 days. %0 conference lecture (invited) %@ %A Abetz, V.,Jung, A.,Hahn, J.,Buhr, K.,Clodt, J.,Rangou, S.,Abetz, C.,Filiz, V. %D 2012 %J 10th International Symposium on Polymer Physics, PP 2012 %N %P %T Self-Assembled Block Copolymer Membranes from Quenched Solutions %U %X %0 conference lecture (invited) %@ %A Abetz, V.,Jung, A.,Hahn, J.,Buhr, K.,Clodt, J.,Rangou, S.,Abetz, C.,Filiz, V. %D 2012 %J World Polymer Congress, MACRO 2012 %N %P %T Self-Assembled Block Copolymer Membranes %U %X %0 conference lecture %@ %A Jung, F.,Mrowietz, C.,Gerk, U.,Franke, R.-P. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Influence of a radiographic contrast media (Iopentol) with different viscosities on capillary perfusion in patients with coronary artery disease %U %X %0 conference lecture %@ %A Jung, F.,Mrowietz, C.,Schulz, C.,Blaschke, F.,Mueller, D.,Lendlein, A.,Schunck, W.-H. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Epoxyeicosatetraenoic acid analogs and Ristozetin-induced platelet aggregation %U %X %0 conference paper %@ 1877-7058 %A Shishatskiy, S.,Buhr, K.,Hahn, J.,Jung, A.,Filiz, V.,Rangou, S.,Abetz, V. %D 2012 %J Procedia Engineering %N %P 1570-1571 %R doi:10.1016/j.proeng.2012.08.868 %T Perfluorinated Compounds as Test Media for Porous Membranes %U https://doi.org/10.1016/j.proeng.2012.08.868 %X No abstract %0 journal article %@ 0920-5063 %A Hiebl, B.,Cui, J.,Kratz, K.,Frank, O.,Schossig, M.,Richau, K.,Lee, S.,Jung, F.,Lendlein, A. %D 2012 %J Journal of Biomaterials Science - Polymer Edition %N 7 %P 901-915 %R doi:10.1163/092050611X566144 %T Viability, Morphology and Function of Primary Endothelial Cells on Poly(Eta-Butyl Acrylate) Networks Having Elastic Moduli Comparable to Arteries %U https://doi.org/10.1163/092050611X566144 7 %X Soft hydrophobic poly(n-butyl acrylate) networks (cPnBA) were developed as entropy elastic substrates for passive mechanical stimulation of cells, where the elastic modulus of the cPnBAs could be systematically adjusted by variation of the cross-link density. The networks were synthesized by thermally-induced radical polymerization from n-butyl acrylate, with poly(propylene glycol) dimethacrylate (PPGDMA) acting as cross-linker, whereby the purity of the cPnBAs was confirmed by (1)H-NMR spectroscopy and gas chromatography. In this work two cPnBA polymer networks with an elastic modulus around 200 kPa and 1 MPa were investigated having an elastic modulus similar to that of arteries. Both cPnBAs exhibited an almost smooth surface with a surface roughness (R(q)) in the wet state ranging from 17 to 37 nm and a similar zeta-potential, indicating an almost identical chemical composition within the topmost surface layer in terms of functional groups. In contrast, wettability of the samples was found to be different with an advancing angle (θ(advancing)) of 1233.8 for cPnBA0250, while for cPnBA1100 significantly lower values for θ(advancing) (1113.8) were obtained. First in vitro tests were performed with primary endothelial cells (HUVEC) to study its effects on vascular cell functions. Within the time period of cultivation (72 h), the cells on the cPnBA samples reached subconfluence and showed a viability rate of almost 100%. Although cell density differed after 72 h with more cells on cPnBA0250 than on cPnBA1100, both materials showed no significant effect on the cell morphology, the cellular LDH-release, which was used as marker for the integrity of the cell membrane, and the organisation of the VE-cadherin. However, lower cell density and less actin stress fibre formation on cPnBA1100 might indicate that cell-material interaction was weaker on cPnBA1100 than on cPnBA0250. The secretion of the vasoactive cytokines prostacyclin (PGI2) and thromboxane A2 (TXA2) was low compared to previously reported values. However, the anti-thrombogenic ratio of PGI2/TXA2 - which is balanced under physiological conditions - with much higher PGI2 compared to TXA2 (up to 17.6-fold after 72 h for cPnBA1100) suggests that this material might be effective to preventing thrombosis. %0 journal article %@ 1877-7058 %A Abetz, V.,Filiz, V.,Rangou, S.,Abetz, C.,Jung, A.,Buhr, K. %D 2012 %J Procedia Engineering %N %P 194-197 %R doi:10.1016/j.proeng.2012.08.355 %T Self–assembled Integral Asymmetric Block Copolymer Membranes: Structure Formation and Properties %U https://doi.org/10.1016/j.proeng.2012.08.355 %X No abstract %0 conference lecture %@ %A Krueger, A.,Mrowietz, C.,Lendlein, A.,Jung, F. %D 2012 %J 14th International Congress of Biorheology, 7th International Conference on Clinical Hemorheology %N %P %T Interaction of human venous endothelial cells with platelets in vitro: Influence of platelet concentration %U %X %0 journal article %@ 0906-6705 %A Trescher, K.,Kratz, K.,Roch, T.,Juenger, M.,Jung, F.,Lendlein, A. %D 2012 %J Experimental Dermatology %N 3 %P e1-e58 %R doi:10.1111/j.1600-0625.2011.01428.x %T Behaviour of primary human keratinocytes and fibroblasts on soft poly(n-butyl acrylate) networks with tailored mechanical properties %U https://doi.org/10.1111/j.1600-0625.2011.01428.x 3 %X No abstract %0 journal article %@ 1386-0291 %A Mrowietz, C.,Franke, R.-P.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 35-47 %R doi:10.3233/CH-2011-1441 %T Influence of different radiographic contrast media on the echinocyte formation of human erythrocytes %U https://doi.org/10.3233/CH-2011-1441 1-2 %X Echinocyte formation is associated with a rigidification of the cells that may affect capillary perfusion and, consequently, the tissue oxygen supply. This study examines how many echinocytes appeared after the addition of radiographic contrast media (RCM) (Iodixanol320, Ioversol300, Iopamidol300, and Iomeprol400) compared to red blood cells in autologous plasma and in isotonic saline solution. Isotonic saline solution, Iodixanol, Ioversol, Iopamidol and Iomeprol in concentrations of 10 vol%, 20 vol%, and 40 vol% were added to the plasma of seven healthy subjects. Subsequently, the erythrocytes were resuspended in these plasma/RCM mixtures, incubated for 5 minutes and then examined under the microscope. The concentrations and the RCM in the mixture had a significant effect on the number of discocytes (factor concentration: p < 0.0001; factor RCM: p < 0.0001). The percentage of discocytes for all concentrations depended significantly on the RCM/plasma mixture (concentration × RCM: p < 0.002). Of all RCM/plasma mixtures used, the Iodixanol/plasma mixture showed the most similar discocyte fraction compared to red blood cells in the autologous plasma. Importantly, while Iodixanol differed from all other RCMs, the other RCMs did not differ from one another with respect to the discocyte fraction. %0 conference lecture %@ %A Abetz, V.,Filiz, V.,Rangou, S.,Abetz, C.,Jung, A.,Buhr, K. %D 2012 %J Euromembrane 2012 %N %P %T Self–assembled Integral Asymmetric Block Copolymer Membranes: Structure Formation and Properties %U %X %0 conference lecture %@ %A Krueger, A.,Braune, S.,Kratz, K.,Lendlein, A.,Jung, F. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T The influence of poly(n-butyl acrylate) networks on viability and function of smooth muscle cells and vascular fibroblasts %U %X %0 conference lecture %@ %A Shishatskiy, S.,Buhr, K.,Hahn, J.,Jung, A.,Filiz, V.,Rangou, S.,Abetz, V. %D 2012 %J Euromembrane 2012 %N %P %T Perfluorinated compounds as test media for porous membranes %U %X %0 conference poster %@ %A Goers, J.,Mayer, A.,Zaupa, A.,Pierce, B.,Neffe, A.T.,Lendlein, A.,Jung, F. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Influence of physically (DAT) crosslinked gelatin on the vasculature in the avian chorioallantoic membrane %U %X %0 conference paper %@ 1877-7058 %A Clodt, J.,Rangou, S.,Filiz, V.,Buhr, K.,Jung, A.,Hahn, J.,Abetz, V. %D 2012 %J Procedia Engineering %N %P 1237-1240 %R doi:10.1016/j.proeng.2012.08.739 %T Postfunctionalisation of Self–assembled Block Copolymer Membranes %U https://doi.org/10.1016/j.proeng.2012.08.739 %X No abstract %0 conference poster %@ %A Roch, T.,Krueger, A.,Kratz, K.,Ma, N.,Jung, F.,Lendlein, A. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Immuno-compatibility of polystyrene and poly(ether imide) with different roughness %U %X %0 conference poster %@ %A Schulz, C.,Lange, M.,Lendlein, A.,Jung, F. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Viability and function of primary human endothelial cells on smooth poly(ether imide) films %U %X %0 conference poster %@ %A Braune, S.,Seifert, B.,Lendlein, A.,Jung, F. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Automated image-based analysis of adherent thrombocytes on polymer surfaces %U %X %0 conference poster %@ %A Trescher, K.,Jung, F.,Scharnagl, N.,Roch, T.,Lendlein, A. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Adherence and viability of primary human keratinocytes and primary human dermal fibroblasts on acrylonitrile based copolymers with increasing amounts of AEMA %U %X %0 conference poster %@ %A Wang, W.,Kratz, K.,Xu, X.,Li, Z.,Roch, T.,Jung, F.,Ma, N.,Lendlein, A. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T The influence of polymeric materials on cellular behaviors of bone marrow derived human mesenchymal stem cells %U %X %0 journal article %@ 1616-5187 %A Pierce, B.F.,Tronci, G.,Roessle, M.,Neffe, A.T.,Jung, F.,Lendlein, A. %D 2012 %J Macromolecular Bioscience %N 4 %P 484-493 %R doi:10.1002/mabi.201100232 %T Photocrosslinked Co-Networks from Glycidylmethacrylated Gelatin and Poly(ethylene glycol) Methacrylates %U https://doi.org/10.1002/mabi.201100232 4 %X Biopolymer-based systems with adjustable macroscopic properties that can be varied in a wide range using only small changes in chemical composition are promising candidates for biomaterial-induced autoregeneration. Glycidylmethacrylated gelatin is photopolymerized with the addition of PEG mono- or dimethacrylate to form co-networks in pH = 7.4 PBS. The degree of swelling (Q) and water uptake (H) in PBS at 37 °C are tailorable for PEGDMA co-networks (Q ≈ 250–650 vol%), while the storage modulus of swollen networks at 37 °C can be adjusted by the PEG(D)MA content (G′ = 0.7–145 kPa). Indirect cytotoxicity tests on ethylene oxide sterilized films show non-toxic responses for the homonetwork and all but one PEGDMA-containing co-networks materials. %0 journal article %@ 1616-5187 %A Pierce, B.F.,Pittermann, E.,Ma, N.,Gebauer, T.,Neffe, A.T.,Hoelscher, M.,Jung, F.,Lendlein, A. %D 2012 %J Macromolecular Bioscience %N 3 %P 312-321 %R doi:10.1002/mabi.201100237 %T Viability of Human Mesenchymal Stem Cells Seeded on Crosslinked Entropy-Elastic Gelatin-Based Hydrogels %U https://doi.org/10.1002/mabi.201100237 3 %X Biomimetic polymer network systems with tailorable properties based on biopolymers represent a class of degradable hydrogels that provides sequences for protein adsorption and cell adhesion. Such materials show potential for in vitro MSC proliferation as well as in vivo applications and were obtained by crosslinking different concentrations of gelatin using varying amounts of ethyl lysine diisocyanate in the presence of a surfactant in pH 7.4 PBS solution. Material extracts, which were tested for cytotoxic effects using L929 mouse fibroblasts, were non-toxic. The hydrogels were seeded with human bone marrow-derived MSCs and supported viable MSCs for the incubation time of 9 d. Preadsorption of fibronectin on materials improved this biofunctionality. %0 conference poster %@ %A Trescher, K.,Kratz, K.,Roch, T.,Juenger, M.,Jung, F.,Lendlein, A. %D 2012 %J 39. Annual Meeting of the Arbeitsgemeinschaft Dermatologische Forschung %N %P %T Behaviour of primary human keratinocytes and fibroblasts on soft poly(n-butyl acrylate) networks with tailored mechanical properties %U %X %0 conference lecture %@ %A Jung, A.,Fierro, D.,Gallei, M.,Rangou, S.,Abetz, C.,Boschetti de Fierro, A.,Filiz, V.,Abetz, V. %D 2012 %J 11th World Filtration Congress, SELFMEM-Symposium %N %P %T Structure Formation of Block Copolymer Membranes %U %X %0 conference poster %@ %A Jung, A.,Buhr, K.,Rangou, S.,Filiz, V.,Abetz, C.,Abetz, V. %D 2012 %J World Filtration Congress %N %P %T Stimuli Responsiveness of Block Copolymer Membranes %U %X %0 journal article %@ 0160-564X %A Mayer, A.,Kratz, K.,Hiebl, B.,Lendlein, A.,Jung, F. %D 2012 %J Artificial Organs %N 3 %P E28-E38 %R doi:10.1111/j.1525-1594.2011.01410.x %T Interaction of angiogenically stimulated intermediate CD163+ monocytes/macrophages with soft hydrophobic poly(n-butyl acrylate) networks with elastic moduli matched to that of human arteries %U https://doi.org/10.1111/j.1525-1594.2011.01410.x 3 %X The cell population of peripheral blood monocytes/macrophages (MO) is heterogeneous: The majority of the MO are CD14++ CD16- and named “classical” (= MO1). Furthermore two other subpopulations were described: CD14++ CD16+ (“intermediate” = MO2) and CD14+ CD16++ (“non-classical” = MO3). It is reported that MO2 posses anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic neutrally charged acrylamide-based hydrogel human intermediate (CD14++ CD16+) CD163++ monocytes/macrophages (aMO2) angiogenically stimulated maintained a pro-angiogenic and non-inflammatory status for at least 14 days. Here we explored whether this aMO2 subset adhered to hydrophobic poly(n-butyl acrylate) networks (cPnBA) and also remained in its pro-angiogenic and non-inflammatory status. Because substrate elasticity can impact adherence, morphology and function of cells, cPnBAs with different Young’s modulus (250 and 1100 kPa) were investigated, whereby their elasticity was tailored by variation of the crosslinker content and matched to the elasticity of human arteries.,The cPnBAs exhibited similar surface properties (e.g. surface roughness), which were maintained after ethylene oxide sterilization and exposure in serum-free cell culture medium for 18 h at 37 °C.,aMO2 were seeded on cPnBA samples (1.7 × 105 cells / 1.33 cm2) in a cell culture medium (DMEM) supplemented with VEGF-A165 (10 ng/ml) and fetal calf serum (10 vol%) for 3 and 72 hrs. On both polymeric samples (n=3 each) the numbers of adherent cells per unit area were significantly higher (p<0.01; cPnBA0250: 3 hrs 13±5 cells/mm2, 72 hrs 234±106 cells/mm2; cPnBA1100: 3 hrs 14±3 cells/mm2, 72 hrs 198±113 cells/mm2) compared to control cultures (glass, 3 hrs: 6±3 cells/mm2, 72 hrs: 130±83 cells/mm2) and showed a typically spread morphology.,The mRNA expression profile of the aMO2 was not influenced by the substrate elasticity. In the supernatant of aMO2 on cPnBA0250 significantly less VEGF-A165 product was found than expected based on the mRNA level measured (p<0.01). Tests with recombinant VEGF-A165 then demonstrated that significantly more VEGF-A165 was adhered on cPnBA0250 than on cPnBA1100 (p<0.01).,Seeded on cPnBA, aMO2 – unaffected by the elastic moduli of both substrates – seemed to remain in their subset status and secreted VEGF-A165 without release of pro-inflammatory cytokines. These in vitro results might indicate that this MO subset can be used as cellular delivery system for pro-angiogenic and non-inflammatory mediators to support the endothelialization of cPnBA. %0 journal article %@ 1386-0291 %A Roch, T.,Cui, J.,Kratz, K.,Lendlein, A.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 131-142 %R doi:10.3233/CH-2010-1449 %T Immuno-compatibility of soft hydrophobic poly (n-butyl acrylate) networks with elastic moduli for regeneration of functional tissues %U https://doi.org/10.3233/CH-2010-1449 1-2 %X The need for engineered devices to treat cardiovascular diseases is increasing due to an aging population and a changing lifestyle. Soft poly(n-butyl acrylate) (cPnBA) networks were recently described as polymer networks with adjustable mechanical properties and suggested as soft substrates for cells, which could potentially be used for cardiovascular implants. Vascular prostheses designed to be implanted in arteries should have an elasticity similar to blood vessels (elastic modulus at body temperature between 100 and 1200 kPa). Therefore, cPnBA networks with E-moduli of 250 kPa (cPnBA0250) and 1100 kPa (cPnBA1100) were developed. Recently, it was shown that both materials were non-cytotoxic for murin fibroblasts, human primary endothelial cells and human monocytes. However, before such newly developed polymers can be used in vivo, it has to be assured that the sterilized materials have a very low endotoxin load to avoid an unspecific activation of the immune system, which otherwise might cause local or systemic inflammatory responses and could lead to severe pathologies. In this study we investigated the immuno-compatibility of sterilized cPnBA0250 and cPnBA1100 with the help of an immuno-competent macrophage cell line as well as with whole human blood. %0 conference lecture %@ %A Clodt, J.,Buhr, K.,Hahn, J.,Jung, A.,Rangou, S.,Filiz, V.,Abetz, V. %D 2012 %J Euromembrane 2012 %N %P %T Postfunctionalisation of Self-Assembled Block Copolymer Membranes %U %X %0 conference poster %@ %A Hahn, J.,Filiz, V.,Rangou, S.,Clodt, J.,Jung, A.,Buhr, K.,Abetz, C.,Abetz, V. %D 2012 %J Euromembrane 2012 %N %P %T Structure formation of integral-asymmetric membranes of Polystyrene-block-Poly(ethylene oxide) %U %X %0 journal article %@ 1386-0291 %A Rueder, C.,Sauter, T.,Becker, T.,Kratz, K.,Hiebl, B.,Jung, F.,Lendlein, A.,Zohlnhoefer, D. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 101-112 %R doi:10.3233/CH-2011-1447 %T Viability, proliferation and adhesion of smooth muscle cells and human umbilical vein endothelial cells on electrospun polymer scaffolds %U https://doi.org/10.3233/CH-2011-1447 1-2 %X A major clinical problem of high relevance in the cardiovascular field is late stent thrombosis after implantation of drug eluting stents (DES). Clinical widely used DES currently utilize durable polymer coatings, which can induce persistent arterial wall inflammation and delayed vascular healing resulting in an impaired endothelialization. In this study we explored the interaction of smooth muscle cells (SMC) and human umbilical vein endothelial cells (HUVEC) with electrospun scaffolds prepared from resorbable polyetheresterurethane (PDC) and poly(p-dioxanone) (PPDO), as well as polyetherimide (PEI), which can be surface modified, in comparison to poly(vinylidene fluoride-co-hexafluoropropene) (PVDF) as reference material, which is established as coating material of DES in clinical applications. Our results show that adhesion could be improved for HUVEC on PDC, PPDO and PEI compared to PVDF, whereas almost no SMC attached to the scaffolds indicating a cell-specific response of HUVEC towards the different fibrous structures. Proliferation and apoptosis results revealed that PPDO and PEI have no significant negative influence on vitality and cell cycle behaviour compared to PVDF. Hence, they represent promising candidates for temporary blood vessel support that induce HUVEC attachment and prevent SMC proliferation. %0 conference paper %@ 1877-7058 %A Hahn, J.,Filiz, V.,Rangou, S.,Clodt, J.,Jung, A.,Buhr, K.,Abetz, C.,Abetz, V. %D 2012 %J Procedia Engineering %N %P 1844-1847 %R doi:10.1016/j.proeng.2012.08.972 %T Structure Formation of Integral-Asymmetric Membranes of Polystyrene-block-poly(ethylene oxide) %U https://doi.org/10.1016/j.proeng.2012.08.972 %X No abstract %0 journal article %@ 1438-7492 %A Jung, A.,Rangou, S.,Abetz, C.,Filiz, V.,Abetz, V. %D 2012 %J Macromolecular Materials and Engineering %N 8 %P 790-798 %R doi:10.1002/mame.201100359 %T Structure Formation of Integral Asymmetric Composite Membranes of Polystyrene-block-Poly(2-vinylpyridine) on a Nonwoven %U https://doi.org/10.1002/mame.201100359 8 %X The formation of an integral asymmetric membrane composed of a cylinder-forming polystyrene-block-poly(2-vinylpyridine) on a nonwoven by using solvent casting followed by solvent/nonsolvent exchange (phase inversion) is reported for the first time. The influence of parameters such as solvent composition, evaporation time of the solution-cast block copolymer film before phase inversion, and immersion bath temperature is demonstrated. The optimized membranes are characterized in terms of stimuli-responsive water flux properties. The morphologies of the membranes as well as of the bulk of the block copolymer are imaged by scanning force microscopy, scanning electron microscopy, and transmission electron microscopy. %0 conference lecture (invited) %@ %A Neffe, A.T.,Pierce, B.F.,Jung, F.,Ma, N.,Lendlein, A. %D 2012 %J Chemistry Seminar Flinders University %N %P %T Biomimetic Polymers for Biomedical Applications %U %X %0 journal article %@ 0268-3555 %A Hiebl, B.,Mueller, C.,Goers, J.,Jung, F.,Lendlein, A.,Juenger, M.,Hamm, B.,Niehues, S.M. %D 2012 %J Phlebology %N 7 %P 337-346 %R doi:10.1258/phleb.2011.011035 %T A NiTi alloy-based cuff for external banding valvuloplasty: a six-week follow-up study in pigs %U https://doi.org/10.1258/phleb.2011.011035 7 %X Objective The study aimed to test a Nitinol®-based vein cuff model for external banding valvuloplasty.,Method In 12 adult minipigs, the vena jugularis externa was covered for 42 days by a cuff with an inner diameter adapted to the outer vein diameter in supine position. By changing from supine into prone position hypostatically vein dilation was induced to simulate varicose vein dilation. Cuff position and the inner diameter of the vein lumen under the cuff were examined by computer tomography scanning. Also, histological analysis of the vein wall within the cuff was performed.,Results The preset tubular shape of the cuff and the cuff position did not change in both prone and supine position, but due to fibrosis the luminal vein diameter within the cuff was decreased (P < 0.01) already after 21 days.,Conclusion A foreign body response resulted in a fibrous capsule covering the cuff which might limit cuff functionality. %0 journal article %@ 1386-0291 %A Leithaeuser, B.,Mrowietz, C.,Park, J.-W.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 25-34 %R doi:10.3233/CH-2011-1440 %T Influence of acetylsalicylic acid (Aspirin) on cutaneous microcirculation %U https://doi.org/10.3233/CH-2011-1440 1-2 %X Background: The protective effect of acetylsalicylic acid (aspirin) in primary and secondary prophylaxis of cardiovascular events is attributed to the inhibition of platelet cyclooxygenase (COX). However, a recent animal study found a vasodilating and blood pressure lowering effect of aspirin independent of COX, but mediated by inhibition of the RhoA/Rho kinase signaling pathway. Method: Prospective, randomized, double-blind, placebo-controlled cross-over study. In each instance 5 healthy volunteers received either aspirin 500 mg/d or placebo for 7 days. Capillary red blood cell velocity (vRBC) at rest and after postischemic hyperemia was determined on day 1 and 7 by means of nailfold capillary microscopy. Results: In the aspirin group after 7 days a significant increase of vRBC was found at rest and during hyperemia. In the placebo group vRBC did not change. The finding was confirmed by the cross-over design of the study. Conclusion: Aspirin at a dosage of 500 mg/d has an impact on vasoregulation in the microcirculation. At present, the underlying mode of action in humans is unknown. %0 journal article %@ 1386-0291 %A Rueder, C.,Sauter, T.,Kratz, K.,Peter, J.,Jung, F.,Lendlein, A.,Zohlnhoefer, D. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 313-323 %R doi:10.3233/CH-2012-1607 %T Smooth muscle and endothelial cell behaviour on degradable copolyetheresterurethane films %U https://doi.org/10.3233/CH-2012-1607 2-4 %X Stent thrombosis and restenosis after drug-eluting stent (DES) implantation remains a relevant problem in the cardiovascular field. The polymer-based biomaterial (e.g. stent coating) requirements are comprehensive, since the polymeric material ideally should ensure an effective re-endothelialization by recruiting endothelial cells (EC) and endothelial progenitor cells (EPC). Simultaneously, the polymer should effectively prevent adherence of smooth muscle cells (SMC) and thereby inhibiting restenosis. The aim of this study was to gain a basic understanding on the interaction of SMC and human umbilical vein endothelial cells (HUVEC) with nonporous polymer films. A multifunctional copolyetheresterurethane (PDC) was chosen as candidate material: PDC consists of poly(p-dioxanone) (PPDO) and poly(ε-caprolactone)-segments (PCL). In our study it was compared to the degradable PPDO homopolymer and poly(vinylidene fluoride-co-hexafluoropropene) (PVDF), an established coating material of DES in clinical applications intended for longterm applications. The films were analyzed according to their thermomechanical and surface properties before being examined in contact with HUVEC and SMC concerning cell viability, proliferation and adhesion. Experimental results showed that adhesion could be improved for HUVEC on PDC compared to PPDO and PVDF. In contrast, SMC attachment is largely suppressed on PDC polymeric films indicating a cell-specific response of HUVEC towards PDC. In conclusion, PDC represents a promising candidate material for future cardiovascular applications like e.g. biodegradable (PDC) stent coatings. %0 conference lecture %@ %A Jung, F. %D 2012 %J VDI Workshop 2012 %N %P %T Vom bare-metal Stent zum Polymerstent: Status und Ausblick Entwicklung %U %X %0 conference lecture %@ %A Xu, X.,Wang, W.,Kratz, K.,Li, Z.,Roch, T.,Jung, F.,Ma, N.,Lendlein, A. %D 2012 %J 14th International Congress of Biorheology, 7th International Conference on Clinical Hemorheology %N %P %T Different polymer surfaces influence in vitro cultivation of rat mesenchymal stem cells %U %X %0 conference poster %@ %A Matschke, K.,Knaut, M.,Kanig, R.,Mrowietz, C.,Hiebl, B.,Jung, F. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Influence of systemic hypothermia on the myocardial oxygen tension during extracorporeal circulation: Comparative study in German Landrace pigs %U %X %0 conference poster %@ %A Gori, T.,Damaske, A.,Muxel, S.,Radmacher, M.-C.,Fasola, F.,Schaefer, S.,Fineschi, M.,Forconi, S.,Jung, F.,Muenzel, T.,Parker, J.D. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Endothelial function and hemorheological parameters modulate coronary blood flow in patients without significant coronary artery disease %U %X %0 conference poster %@ %A Neffe, A.T.,Zaupa, A.,Pierce, B.F.,Roch, T.,Jung, F.,Lendlein, A. %D 2012 %J COST Namabio 2nd Joint Meeting %N %P %T Functionalization of Gelatin with Tyrosine Moieties: A Supramolecular Approach to Biomaterials %U %X %0 conference poster %@ %A Scharnagl, N.,Hiebl, B.,Trescher, K.,Zierke, M.,Behl, M.,Kratz, K.,Jung, F.,Lendlein, A. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Behaviour of fibroblasts on water born acrylonitrile based copolymers with different densities of positive and negative surface charges %U %X %0 journal article %@ 1386-0291 %A Braune, S.,Alagoez, G.,Seifert, B.,Lendlein, A.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 349-355 %R doi:10.3233/CH-2012-1610 %T Automated image-based analysis of adherent thrombocytes on polymer surfaces %U https://doi.org/10.3233/CH-2012-1610 2-4 %X A dataset of 439 confocal laser scanning microscopic images was analyzed to investigate the potential of an image-based automated analysis for identifying and assessing adherent thrombocytes on polymer surfaces. Parameters for image optimization of glutardialdehyde induced fluorescence images were classified and data mining was performed using the Java image processing software ImageJ. Previously reported analysis required that each thrombocyte had to be identified interactively and outlined manually. Now, we were able to determine the number and area of adherent thrombocytes with high accuracy (spearman correlation coefficient r = 0.98 and r = 0.99) using a two-stage filter-set, including a rolling ball background subtraction- and a watershed segmentation-algorithm. Furthermore, we could proof a significant correlation between these parameters (spearman correlation coefficient r = 0.97), determining both as suitable predictors for the evaluation of material induced thrombogenicity. The here reported image-based automated analysis can be successfully applied to identify and measure adherent thrombocytes on polymer surfaces and, thus, might be successfully integrated in a high-throughput screening process to evaluate biomaterial hemocompatibility. %0 journal article %@ %A Wischke, C.,Kratz, K.,Jung, F.,Lendlein, A. %D 2012 %J BioTOPics : Journal of Biotechnology in Berlin-Brandenburg %N %P 5-7 %T Helmholtz Virtual Institute „Multifunctional Materials for Medicine“ %U %X Modern medicine is exploring novel strategies for curative therapies like minimally-invasive treatment procedures, approaches,for inducing endogenous regeneration, and targeted drug delivery, which are based on innovative multifunctional,polymeric biomaterials. Since protein-biomaterial surface interactions can critically affect the performance of such,materials in a biological environment, the strategic goal of the new Helmholtz Virtual Institute „Multifunctional Materials,for Medicine“ is to gain a comprehensive understanding of these complex processes in order to control the applicationrelevant,protein adsorption behaviour in the future. The activities of this Helmholtz Virtual Institute initiative are integrated,into the regional cluster “Healthcare Industry Berlin-Brandenburg – Health Capital”. %0 conference lecture %@ %A Ma, N.,Xu, X.,Kratz, K.,Li, Z.,Roch, T.,Jung, F.,Lendlein, A. %D 2012 %J 14th International Congress of Biorheology, 7th International Conference on Clinical Hemorheology %N %P %T The influence of polymeric materials on mesenchymal stem cells cellular behaviors %U %X %0 conference lecture %@ %A Braune, S.,Krueger, A.,Walter, M.,Schiemann, M.,Kratz, K.,Kuepper, J.-H.,Jung, F.,Lendlein, A. %D 2012 %J 39th Congress of the European Society for Artificial Organs, ESAO 2012 %N %P %T Influence of different surface treatment of poly(n-butyl acrylate) networks on L929 mouse fibroblasts adhesion and viability %U %X %0 conference lecture (invited) %@ %A Rueder, C.,Sauter, T.,Kratz, K.,Peter, J.,Jung, F.,Lendlein, A.,Zohlnhoefer, D. %D 2012 %J 31. Jahrestagung der Deutschen Gesellschaft fuer klinische Mikrozirkulation und Haemorheologie %N %P %T Smooth muscle and endothelial cell behaviour on polymeric films with different chemical compositions %U %X %0 conference lecture (invited) %@ %A Lendlein, A.,Jung, F. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %N %P %T Biomaterials for Cardiovascular Applications - Challenges and Concepts %U %X %0 conference poster %@ %A Braune, S.,Krueger, A.,Kratz, K.,Lendlein, A.,Jung, F. %D 2012 %J 14th International Congress of Biorheology, 7th International Conference on Clinical Hemorheology %N %P %T Influence of randomized biomaterial micropatterning on platelet adhesion and activation %U %X %0 conference lecture %@ %A Jung, F.,Lendlein, A. %D 2012 %J Biologisierung der Medizintechnik - Evolution oder Revolution? Strategieworkshop %N %P %T Biofunktionale Materialsysteme fuer die Medizintechnik %U %X %0 journal article %@ 1386-0291 %A Franke, R.P.,Fuhrmann, R.,Mrowietz, C.,Hiebl, B.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 49-54 %R doi:10.3233/CH-2010-1442 %T Do radiographic contrast media (Iodixanol or Iomeprol) induce a perturbation of human arterial and/or venous endothial cells in vitro on extracellular matrix? %U https://doi.org/10.3233/CH-2010-1442 1-2 %X After intra-arterial administration of several radiographic contrast media (RCM) a disorder of the downstream microcirculation with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure in the myocardium of the pig heart was described. Iodixanol did not induce such a microcirculatory disorder in the myocardium of the beating heart of pigs. Whether the morphological changes reported in venous endothelial cells after incubation in culture media supplemented with RCM in vitro coincide with a serious endothelial cell dysfunction is not known. In this study we wanted to get information on possible states of dysfunction or perturbation of venous and arterial ECs through the release of prostacyclin, which was shown to follow the perturbation of ECs. Functionally confluent venous endothelial cells on extracellular matrix secreted great amounts of prostacyclin in reaction to the RCMs indicating a clear perturbation of the ECs. This was not the case in arterial EC cultures. The prostacyclin release from arterial ECs exposed to Iodixanol was more than 10-fold higher than that from arterial ECs exposed to Iomeprol. This could be one of the important factors contributing to the undisturbed myocardial microcirculation after injection of Iodixanol despite a slight echinocyte formation. %0 journal article %@ 1022-1336 %A Lange, M.,Braune, S.,Luetzow, K.,Richau, K.,Scharnagl, N.,Weinhart, M.,Neffe, A.T.,Jung, F.,Haag, R.,Lendlein, A. %D 2012 %J Macromolecular Rapid Communications %N 17 %P 1487-1492 %R doi:10.1002/marc.201200426 %T Surface Functionalization of Poly(ether imide) Membranes with Linear, Methylated Oligoglycerols for Reducing Thrombogenicity %U https://doi.org/10.1002/marc.201200426 17 %X Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers. %0 journal article %@ 1386-0291 %A Jung, F.,Schulz, C.,Blaschke, F.,Muller, D.N.,Mrowietz, C.,Franke, R.P.,Lendlein, A.,Schunck, W.-H. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 403-416 %R doi:10.3233/CH-2012-1614 %T Effect of cytochrome P450-dependent epoxyeicosanoids on Ristocetin-induced thrombocyte aggregation %U https://doi.org/10.3233/CH-2012-1614 2-4 %X Epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 (CYP)-dependent epoxidation of arachidonic acid (AA) inhibit thrombocyte adhesion to the vascular wall. Upon dietary omega-3 fatty acid supplementation, EETs are partially replaced by eicosapentaenoic acid (EPA)-derived epoxyeicosatetraenoic acids (EEQs) and docosahexaenoic acid (DHA)-derived epoxydocosapentaenoic acids (EDPs). We hypothesized that the omega-3 epoxy-metabolites may exhibit superior anti-thrombogenic properties compared to their AA-derived counterparts. To test this hypothesis, we analyzed the effects of 11,12-EET, 17,18-EEQ and 19,20-EDP on Ristocetin-induced thrombocyte aggregation (RITA), a process that mimics thrombocyte adhesion to the vascular wall. The eicosanoids were added for 5, 30, or 60 minutes to thrombocyte-rich plasma freshly prepared immediately after blood collection from stringently selected apparently healthy subjects. Thrombocyte aggregation was then induced by Ristocetin (0.75 mg/mL) and assessed by turbidimetric measurements. After 60 minutes of preincubation, all three epoxy-metabolites significantly decreased the rate of RITA. 17,18-EEQ and 19,20-EDP were effective already at 1 μM, whereas 5-fold higher concentrations were required with 11,12-EET. Addition of AUDA, an inhibitor of the soluble epoxide hydrolase, potentiated the effect of 17,18-EEQ resulting in a significant further decrease of the velocity as well as amplitude of the aggregation process. In contrast to their profound effects on RITA, none of the epoxy-metabolites was effective in reducing collagen- or ADP-induced thrombocyte aggregation. These results indicate a highly specific role of CYP-eicosanoids in preventing thromboembolic events and suggest that the formation of 17,18-EEQ and 19,20-EDP may contribute to the anti-thrombotic effects of omega-3 fatty acids. %0 journal article %@ 1386-0291 %A Krueger, A.,Braune, S.,Kratz, K.,Lendlein, A.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 283-294 %R doi:10.3233/CH-2012-1605 %T The influence of poly(n-butyl acrylate) networks on viability and function of smooth muscle cells and vascular fibroblasts %U https://doi.org/10.3233/CH-2012-1605 2-4 %X Background: The patency of small-diameter vascular prostheses is limited by several factors such as thrombogenicity, which is strongly influenced by surface roughness and chemical composition, or a mechanical mismatch between the elastic modulus of an artery and of the vascular prosthesis. A confluent layer of endothelial cells onto the inner surface of vascular prostheses could improve the hemocompatibility of the device. Biomaterials with adjustable elastic properties could be tailored to the values of human arteries so that a prothesis mismatch could be avoided. It was recently demonstrated that a co-culture of endothelial cells with angiogenically stimulated monocytes (aMO2) shows an accelerated formation of a functional confluent endothelial cell monolayer on soft hydrophobic poly(n-butyl acrylate) (cPnBA) networks. In addition, the cell compatibility with vascular smooth muscle cells and aortic fibroblasts, which are other important cell types of the vessel wall, is essential for a vascular prosthesis material and must therefore be explored. Purpose: Here we investigated the interaction of human vascular smooth muscle cells and aortic fibroblasts with cPnBA04 and cPnBA73. Material and methods: Human primary vascular smooth muscle cells and aortic fibroblasts were seeded on the two cPnBAs with different elastic moduli (cPnBA04 - 250 kPa and cPnBA73 - 1100 kPa) over 72 h. A live-dead staining (fluorescein diacetate/propium iodide) was performed to determine the morphology and viability of adherent cells. Furthermore, the extracellular matrix components, the actin cytoskeleton, the cell-material-contacts and the cytokine profiles were analysed. Results: Both cell types adhered and were viable on cPnBA04 and cPnBA73. The level of pro-inflammatory cytokine secretion (IFN-γ and TNF-α) by smooth muscle cells and vascular fibroblasts was comparable to that of cells cultivated on a control material. The release of these cytokines by human fibroblasts was higher on cPnBA73 compared to cPnBA04. Both cell types secreted an extracellular matrix comparable to cells seeded on a control material. Conclusion: The study revealed, that cPnBA with varying elastic moduli are not only suitable for the cultivation of endothelial cells, but also for human vascular smooth muscle cells and aortic fibroblasts. Therefore, cPnBA could be a potential candidate material for the development of cardiovascular prostheses. %0 conference lecture (invited) %@ %A Neffe, A.T.,Behl, M.,Jung, F.,Pierce, B.F.,Lendlein, A. %D 2012 %J Smart Collaborations Seminar %N %P %T Biopolymer-Based Materials for Medical Applications %U %X %0 conference poster %@ %A Neffe, A.T.,Lange, M.,Braune, S.,Luetzow, K.,Jung, F.,Scharnagl, N.,Richau, K.,Weinhart, M.,Haag, R.,Lendlein, A. %D 2012 %J Advanced Functional Polymers for Medicine, AFPM 2012 %N %P %T Surface Functionalization of Poly(ether imide) with Linear, Methylated Oligoglycerols to Increase the Hemocompatibility %U %X %0 journal article %@ 1386-0291 %A Wang, W.,Ma, N.,Kratz, K.,Xu, X.,Li, Z.,Roch, T.,Bieback, K.,Jung, F.,Lendlein, A. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 357-373 %R doi:10.3233/CH-2012-1611 %T The influence of polymer scaffolds on cellular behaviour of bone marrow derived human mesenchymal stem cells %U https://doi.org/10.3233/CH-2012-1611 2-4 %X Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into a variety of cell types. Therefore, they are widely explored in regenerative medicine. The interaction of MSCs with biomaterials is of great importance for cell proliferation, differentiation and function, and can be strongly influenced by numerous factors, such as the chemical nature and the mechanical properties of the material surface. In this study, we investigated the interaction of bone marrow derived human MSCs with different amorphous and transparent polymers namely polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI), polyetherurethane (PEU) and poly(styrene-co-acrylonitrile) (PSAN). To ensure that the MSCs were solely in contact to the testing material we applied polymeric inserts, which were prepared from the aforementioned polymers via injection molding. The explored inserts exhibited a similar wettability with advancing contact angles ranging from 84 ± 7° (PEU) to 99 ± 5° (PS) and a surface roughness of Rq ≤ 0.86 μm. The micromechanical properties determined by AFM indentation varied from 6 ± 1 GPa (PEU) to 24 ± 5 GPa (PSAN). Cells presented different adhesion rates on the polymer surfaces 24 hours after seeding (45 ± 7% (PS), 63 ± 1% (PC), 75 ± 4% (PEI), 69 ± 2% (PEU) and 61 ± 5% (PSAN)). The cells could proliferate on the polymer surfaces, and the fold change of cell number after 16 days of culture reached to 1.93 ± 0.07 (PS), 3.38 ± 0.11 (PC), 3.65 ± 0.04 (PEI), 2.24 ± 0.15 (PEU) and 3.36 ± 0.09 (PSAN). Differences in cell apoptosis could be observed during the culture. After 7 days, the apoptosis of cells on PC, PEI and PSAN decreased to a level comparable to that on standard tissue culture plate (TCP). All of the tested polymers exhibited low cytotoxicity and allowed high cell viability. Compared to cells on TCP, cells on PC and PEI showed similar morphology, distribution as well as F-actin cytoskeleton organization, whereas cells on PSAN were distributed less evenly and cells on PEU were less oriented. Cells were more likely to form clusters on PS. Conclusively, we demonstrated the influence of polymer substrates on the cellular behaviour of MSCs, which could be included in the development of novel design concepts based on polymeric biomaterials. %0 journal article %@ 1386-0291 %A Roch, T.,Krueger, A.,Kratz, K.,Ma, N.,Jung, F.,Lendlein, A. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 375-389 %R doi:10.3233/CH-2012-1612 %T Immunological evaluation of polystyrene and poly(ether imide) cell culture inserts with different roughness %U https://doi.org/10.3233/CH-2012-1612 2-4 %X For the successful clinical and biological application of polymers, their interaction with cells, tissues, and body fluids has to be well characterized. In order to investigate how the physical, chemical, and mechanical properties of candidate biomaterials influence cell behaviours, the testing sample is usually placed in commercially available cell culture plates. Thus, not only the testing sample itself but also the culture dish material might influence the cell behaviour. Therefore, an insert system was created to exclude this influence and allow investigations of the testing material solely. In this study micropatterned inserts prepared from polystyrene (PS) as well as from poly(ether imide) (PEI) with three different roughness levels of i) Rq = 0.12 μm (PS) and 0.23 μm (PEI); ii) Rq = 3.52 μm (PS) and 3.92 μm (PEI); and iii) Rq = 16.04 μm (PS) and 22.65 μm (PEI) were explored with regard of their immuno-compatibility including the determination of potential contaminations with endotoxins or other microbial products. The endotoxin levels of the inserts were determined to be less than 0.07 EU/mL, which is well below the U.S. Food and Drug Administration limit of 0.5 EU/mL and the survival of murine macrophages cultured in the inserts was not impaired. Activation of early immune mechanisms such as complement activation and the generation of reactive oxygen species could not be observed. All tested materials had no influence on the cytokine secretion from cells of whole human blood. The investigated inserts were immuno-compatible and apparently free of contaminations with microbial products. The roughness of the inserts had no stimulatory or inhibitory effect on early immune mechanisms. Conclusively, the 24-well plate insert systems introduced in this study allow investigating the interactions of tailored surface properties such as roughness with many other cell types, without the disadvantage of the standard commercially available culture vessels influencing the biomaterial testing. %0 journal article %@ 1386-0291 %A Jung, F.,Goers, J.,Roch, T.,Zaupa, A.,Pierce, B.,Neffe, A.T.,Lendlein, A. %D 2012 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 55-63 %R doi:10.3233/CH-2011-1443 %T Physically crosslinked gelatins functionalized with tyrosine moieties do not induce angiogenesis or thrombus formation in the developing vasculature in the avian chorioallantoic membrane %U https://doi.org/10.3233/CH-2011-1443 1-2 %X Gelatins functionalized with desaminotyrosine or desaminotyrosyl tyrosine form physically crosslinked polymer networks due to the interactions between the introduced aromatic moeties. In the swollen state, their mechanical properties can be tailored in a range similar to the elasticity of soft tissues. The aim of this study was to evaluate their potential as biomaterials by determining whether these materials – in comparison to plain gelatin – induce bleedings, thrombotic processes, or angiogenesis. These investigations were performed using the hen's egg chorioallantoic membrane (HETCAM) assay. These results indicate that the gelatin-based hydrogels did not possess angiogenic effects and also did not induce bleedings, thrombotic processes or vessel destruction (avascular zones). The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (1 hour up to several days). %0 journal article %@ 1386-0291 %A Scharnagl, N.,Hiebl, B.,Trescher, K.,Zierke, M.,Behl, M.,Kratz, K.,Jung, F.,Lendlein, A. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 295-311 %R doi:10.3233/CH-2012-1606 %T Behaviour of fibroblasts on water born acrylonitrile-based copolymers containing different cationic and anionic moieties %U https://doi.org/10.3233/CH-2012-1606 2-4 %X The chemical composition of a substrate can influence the adhesion, viability and proliferation of cells seeded on the substrate. The aim of this work was to investigate the influence of different cationic or anionic moieties in acrylonitrile-based copolymers on the interaction with fibroblasts. A series of ten different types of acrylonitrile-based copolymers with a random sequence structure was prepared using a water born synthesis process to exclude potential residues of organic solvents. As charged comonomers cationic methacrylic acid-2-aminoethylester hydrochloride (AEMA), N-3-amino-propyl-methacrylamide hydrochloride (APMA) and anionic 2-methyl-2-propene-1-sulfonic acid sodium salt (NaMAS) were utilized. By application of a specific sintering procedure the copolymer materials were processed into transparent disks for conducting cell tests in direct contact. The copolymers were analyzed with respect to their composition and surface properties. Cytotoxicity tests of the polymer extracts, as well as of the disks were performed with L929 mouse fibroblasts. All copolymers showed no cytotoxic effects. Furthermore, for higher molar ratios of AEMA an increase in cell growth could be observed, which might be a hint that higher charge densities are favorable for the proliferation of L929 cells. %0 conference lecture (invited) %@ %A Neffe, A.T.,Pierce, B.F.,Jung, F.,Ma, N.,Lendlein, A. %D 2012 %J Chemistry Seminar University of Adelaide %N %P %T Biomimetic Polymers for Biomedical Applications %U %X %0 journal article %@ 1386-0291 %A Schulz, C.,Ruesten-Lange, M.v.,Krueger, A.,Lendlein, A.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 267-282 %R doi:10.3233/CH-2012-1604 %T Viability and function of primary human endothelial cells on smooth poly(ether imide) films %U https://doi.org/10.3233/CH-2012-1604 2-4 %X Poly(ether imide) (PEI) is being explored as potential biomaterial for cardiovascular applications. Different studies showed that human umbilical venous endothelial cells (HUVEC) are able to adhere and proliferate on PEI membranes (Rq = 13.20 ± 1.58 nm). A recently published study revealed evidence for much lower platelet adhesion on very smooth PEI-films (Rq = 2.37 ± 1.40 nm). Therefore, we explored whether primary human venous endothelial cells (HUVEC) are able to adhere and proliferate on such very smooth PEI-films compared to tissue-cultured polystyrene (TCP) as reference material. Cytotoxicity testing revealed that PEI had a slight cytotoxic effect on HUVEC accompanied by a marginal reduced integrity of the plasma membrane and a significant lower mitochondrial activity. However long-term seeding experiments up to eleven days exhibited that HUVEC were able to proliferate on the PEI-films till confluence (TCP 96,190 ± 18,289 cells/cm2; PEI 91,590 ± 19,583 cells/cm2). Further studies are planned to monitor the influence of shear force on the endothelial cell monolayer in a dynamic test system to determine its stability in view of shear resistant endothelialization of PEI for cardiovascular devices. %0 journal article %@ 1386-0291 %A Matschke, K.,Knaut, M.,Kanig, R.,Mrowietz, C.,Hiebl, B.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 115-122 %R doi:10.3233/CH-2012-1589 %T Influence of systemic hypothermia on the myocardial oxygen tension during extracorporeal circulation: Comparative study in German Landrace pigs %U https://doi.org/10.3233/CH-2012-1589 2-4 %X During extracorporeal circulation (ECC) controlled hypothermia is a common method of myocardial protection due to a reduction of the myocardial oxygen consumption. Although the beneficial aspects of hypothermia on the myocardial metabolism have been widely demonstrated the effect of hypothermia on the myocardial oxygen tension (PmyO2) is unclear. For this reason the PmyO2 of German Landrace pigs (male, three months of age) during ECC was analysed under mild hypothermia (32°C, n = 6 pigs) and under normothermia (n = 10 pigs, control group) within a time period of 23 min (1400 sec). Flexible invasive Clark type microcatheters were used to measure the PmyO2 in the beating heart. During normothermal ECC a continuous PmyO2 increase from 36.5 ± 15.8 mmHg to 52.6 ± 27.2 mmHg (+44.1%) after 1400 sec was measured (p = 0.02). In contrast, mild hypothermia caused a continuous PmyO2 decrease from initially 46.9 ± 17.5 mmHg to 36.7 ± 20.8 mmHg (−21.8%, p < 0.013) in the test period. Electrocardiography revealed no signs of ischemia or arrhythmia during normo- and hypothermic ECC. It seems obvious that mild hypothermia results in a reduction of the oxygen transfer to the myocardial cells and that this effect outweighs the beneficial effects of hypothermia in the myocardium which are related to reduced oxygen consumption. However, in mild hypothermia oxygen supply to the myocardium remained sufficient for normal myocardial function. %0 journal article %@ 1386-0291 %A Gori, T.,Damaske, A.,Muxel, S.,Radmacher, M.-C.,Fasola, F.,Schaefer, S.,Fineschi, M.,Forconi, S.,Jung, F.,Muenzel, T.,Parker, J.D. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 255-266 %R doi:10.3233/CH-2012-1603 %T Endothelial function and hemorheological parameters modulate coronary blood flow in patients without significant coronary artery disease %U https://doi.org/10.3233/CH-2012-1603 2-4 %X Background: Coronary (micro)vascular resistance is regulated by the complex interplay of several factors. Two potentially important determinants include endothelial function and the rheological properties of blood. However, their impact on the control of the coronary resistance vasculature is poorly understood. Methods: The corrected Thrombolysis In Myocardial Infarction frame count (TIMIfc, an index of coronary flow velocity), conduit artery endothelial function, intima-media thickness of the common carotid artery and complete blood counts were measured in 145 patients undergoing elective coronary angiography. Patients with obstructive coronary artery disease or systemic conditions thought to be associated with microvascular disease were excluded from the analysis. Results: There was a strong correlation between the TIMIfc measured in the three main coronary artery distributions (R values between 0.71 and 0.85, P < 0.00001). The TIMIfc was higher in males (P < 0.05), but there was no association with traditional risk factors for coronary artery disease (all P > 0.1). There was a correlation between TIMIfc and L-FMC, a parameter of resting endothelial function (R = 0.33, P < 0.0005). TIMIfc also correlated with mean platelet volume (a marker of platelet activation, R = 0.33, P < 0.001), and hematocrit (R = 0.33, P = 0.0002). There was no correlation between TIMIfc and carotid intima-media thickness and the degree of coronary atherosclerosis. Logistic regression analysis showed that L-FMC and hemorheological variables may explain as much as 19% of the variability in TIMIfc. Conclusions: Resting peripheral endothelial function, as well as parameters of platelet function, correlate with coronary TIMIfc. These data emphasize the existence of an association between endothelial function, hemorheological variables and coronary blood flow velocity. %0 journal article %@ 1386-0291 %A Trescher, K.,Scharnagl, N.,Kratz, K.,Roch, T.,Lendlein, A.,Jung, F. %D 2012 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 391-401 %R doi:10.3233/CH-2012-1613 %T Adherence and viability of primary human keratinocytes and primary human dermal fibroblasts on acrylonitrile-based copolymers with different concentrations of positively charged functional groups %U https://doi.org/10.3233/CH-2012-1613 2-4 %X As shown in several studies, various properties of biomaterials such as stiffness, surface roughness, chemical composition or the amount of functional groups at the surface can influence adhesion, viability, proliferation and functionalities of cells. The aim of this work was to explore whether a cell-selective effect could be achieved for acrylonitrile-based copolymers containing different contents of positively charged functional groups, which were introduced by incorporation of methacrylic acid-2-aminoethylester hydrochloride (AEMA) units. The p(AN-co-AEMA) copolymers were synthesized by suspension polymerization in water and processed into disk shaped test specimen via a sintering process to ensure the absence of organic solvents in the copolymers. Copolymers with an AEMA content of 1.4, 1.6, and 4.4 mol-% were investigated according to their cell-selective capacity, which should support the adhesion, viability and proliferation of keratinocytes, while the adherence of fibroblasts should rather be disabled. The test samples were seeded with primary human keratinocytes and primary human dermal fibroblasts in mono- as well as in co-cultures. Tissue culture plate polystyrene (TCP) was used to control the physiologic growth of the cells. Density and viability of attached and non-adherent cells were analyzed by live/dead staining, lactate dehydrogenase (LDH) assay and flow cytometry with DAPI staining. For the assured discrimination of adherent cell types in coculture a keratin/vimentin-staining was performed. On copolymers with 4.4 mol-% AEMA adherent keratinocytes in monoculture and cocultured keratinocytes and fibroblasts showed a higher viability, a lower impairment of cell membranes and higher densities of viable cells compared to both other copolymers. For adherent fibroblasts these parameters did not differ between the copolymers and an increasing ratio of keratinocytes to fibroblasts in cocultures were found with increasing AEMA content. The results showed that keratinocytes and fibroblasts can be influenced by copolymers with different contents of positively charged functional groups. Since the tendency of a better adherence and viability of keratinocytes with increasing amounts of positively charged functional groups was shown, the potential enhancement by further increase of the amount of positively charged functional groups shall be tested in a future study. %0 conference lecture %@ %A Mrowietz, C.,Franke, R.-P.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Influence of different radiographic contrast media on the echinocyte formation of human erythrocytes %U %X %0 conference poster %@ %A Roch, T.,Pierce, B.F.,Zaupa, A.,Goers, J.,Jung, F.,Neffe, A.T.,Lendlein, A. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Analysis of Endotoxin Content and Evaluation of Angiogenic Effects of Desaminotyrosine- and Desaminotyrosyl Tyrosine-Functionalized Gelatin %U %X %0 journal article %@ 1386-0291 %A Jung, F.,Mrowietz, C.,Hiebl, B.,Franke, R.P.,Pindur, G.,Sternitzky, R. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-3 %P 129-139 %R doi:10.3233/CH-2011-1392 %T Influence of rheological parameters on the velocity of erythrocytes passing nailfold capillaries in humans %U https://doi.org/10.3233/CH-2011-1392 1-3 %X One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role. %0 journal article %@ 1386-0291 %A Gori, T.,Jung, F. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-3 %P 1-3 %R doi:10.3233/CH-2011-1432 %T Perspectives in Clinical Hemorheology and Microcirculation: Review of the Conference of the German Society for Clinical Microcirculation and Hemorheology 2010 %U https://doi.org/10.3233/CH-2011-1432 1-3 %X No abstract %0 conference lecture %@ %A Mayer, A.,Kratz, K.,Hiebl, B.,Lendlein, A.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Interaction of primary CD14+ CD163+ VEGF-A165+ monocytes/macrophages with soft hydrophobic poly(n-butyl acrylate) networks with elastic moduli matched to human arteries %U %X %0 conference poster %@ %A Rueder, C.,Sauter, T.,Becker, T.,Kratz, K.,Hiebl, B.,Jung, F.,Lendlein, A.,Zohlnhoefer, D. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Viability, proliferation, apoptosis and adhesion of smooth muscle cells (SMCs) and endothelial cells (HUVECs) on degradable electro-spun structures %U %X %0 conference lecture %@ %A Mayer, A.,Kratz, K.,Hiebl, B.,Lendlein, A.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Support of HUVEC proliferation by pro-angiogenic intermediate CD163+ monocytes/macrophages: A co-culture experiment %U %X %0 conference poster %@ %A Roch, T.,Mayer, A.,Kratz, K.,Cui, J.,Lendlein, A.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Immuno-compatibility of soft hydrophobic poly(n-butyl acrylate) networks with elastic moduli for regeneration of functional tissues %U %X %0 journal article %@ 1386-0291 %A Franke, R.-P.,Fuhrmann, R.,Hiebl, B.,Jung, F. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-3 %P 41-56 %R doi:10.3233/CH-2011-1404 %T Influence of radiographic contrast media (Iodixanol und Iomeprol) on the morphology of human arterial and venous endothelial cells on extracellular matrix in vitro %U https://doi.org/10.3233/CH-2011-1404 1-3 %X After intra-arterial administration of radiographic contrast media (RCM), a disorder of the downstream microcirculation both with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure was described. Possible factors contributing to this microcirculatory disorder are increase in plasma viscosity, a formation of echinocytes, a buckling and denudation of endothelial cells, and a disturbation of endothelial prostacyclin release. It is not known so far whether the reactions observed in the context of RCM applications are reactions of venous endothelial cells alone or also of arterial endothelial cells. Therefore, arterial ECs on ECM were exposed to the same RCMs under identical conditions. The decrease of cell-cell contacts with an increase of denuded subendothelial matrix areas in the functionally confluent endothelial cell layer on ECM were more pronounced after a five minute exposure of endothelial cells to Iomeprol compared to Iodixanol. Changes in arterial ECs after the incubation in culture media supplemented with RCM were very subtle in comparison to changes in venous ECs. %0 conference poster %@ %A Schneider, T.,Kohl, B.,Sauter, T.,Becker, T.,Kratz, K.,Schossig, M.,Hiebl, B.,Jung, F.,Lendlein, A.,Ertel, W.,Schulze-Tanzil, G. %D 2011 %J Advanced Functional Polymers for Medicine, AFPM 2011 %N %P %T Viability, adhesion and differentiated phenotype of articular chondrocytes on degradable polymers and electro-spun structures thereof %U %X %0 conference poster %@ %A Braune, S.,Hoenow, A.,Mrowietz, C.,Lendlein, A.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Thrombogenicity of Poly(n-butylacrylat) networks %U %X %0 journal article %@ 1386-0291 %A Endres, S.,Hiebl, B.,Haegele, J.,Beltzer, C.,Fuhrmann, R.,Jaeger, V.,Almeida, M.,Costa, E.,Santos, C.,Traupe, H.,Jung, E.M.,Prantl, L.,Jung, F.,Wilke, A.,Franke, R.-P. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-3 %P 29-40 %R doi:10.3233/CH-2011-1406 %T Angiogenesis and healing with non-shrinking, fast degradeable PLGA/CaP scaffolds in critical-sized defects in the rabbit femur with or without osteogenically induced mesenchymal stem cells %U https://doi.org/10.3233/CH-2011-1406 1-3 %X Cost effective and safely to apply tissue engineered constructs of big volume bone transplants for the reconstruction of critical sized defects (CSD) are still not available. Key problems with synthetic scaffold materials are shrinkage and fast degradation of the scaffolds, a lack of blood supply and nutrition in the central scaffold volume and the absent or the scarce development of bone tissue along the scaffold to bridge the bone defect. The use of composite scaffolds made of biopolymers like polylactidglycolid acid (PLGA) coated and loaded with calcium phosphates (CaP) revealed promising therapeutical options for the regeneration of critical sized bone defects. In this study interconnectively macroporous PLGA scaffolds loaded with microporous and coated with nanoporous calcium phosphates were either seeded in fixed bed bioreactors with allogenic osteogenically induced mesenchymal stem cells and implanted or implanted unseeded into critical sized femoral bone defects. As CSD a 12 mm long segment of the chinchilla femur was excised where the proximal and distal parts of the femur were fixed and stabilized by the use of an eight-hole linear reconstruction plate and secured with three bicortical screws (2.7 mm diameter) on every side of the osteotomy. Aim of the study was if we could find a way to load and coat PLGA scaffolds with CaP so that shrinkage of scaffolds could be avoided, which would favour angiogenesis, blood supply and nutrition in the construct and thus avoid central necroses regularly observed so far in transplants not vascularized and which would be inhabited by cells of he bone lineage forming new bone and healing the defect. Four weeks, at least, a notable shrinkage of the scaffolds was avoided and scaffolds were practically not degraded. Both scaffolds, loaded and loaded and coated, revealed blood vessels in all parts of the implants after 4 weeks. Only in scaffolds seeded with allogenic mesenchymal stem cells the development of bridging bone constructs between proximal and distal edges of the femur was observed after four weeks without further supplementation of growth factors. In case of the implantation of non-seeded scaffolds no obvious scaffold bound bone development could be shown. %0 conference lecture %@ %A Mrowietz, C.,Hiebl, B.,Schunk, W.-H.,Mueller, D.,Blaschke, F.,Franke, R.-P.,Lendlein, A.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Effects of Tacrolimus or Sirolimus on the adhesion of vascular wall cells: controlled in-vitro comparison study %U %X %0 report part %@ %A Jung, F.,Lendlein, A. %D 2011 %J Technologiereport - Regenerative Medizin in Berlin-Brandenburg %N %P 78-80 %T Biofunktionale Implantate %U %X %0 conference lecture %@ %A Mrowietz, C.,Peuker, A.,Schunk, W.-H.,Blaschke, F.,Mueller, D.,Lendlein, A.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Influence of different Cytochrom-P450 Eicosanoids on the Ristocetin-induced platelet aggregation %U %X %0 book part %@ %A Rickert, D.,Hiebl, B.,Fuhrmann, R.,Jung, F.,Lendlein, A.,Franke, R.-P. %D 2011 %J Handbook of Biodegradable Polymers: Synthesis, Characterization and Applications %N %P 309-340 %T Regenerative Medicine: Reconstruction of Tracheal and Pharyngeal Mucosal Defects in Head and Neck Surgery %U %X %0 journal article %@ 1386-0291 %A Mayer, A.,Lee, S.,Lendlein, A.,Jung, F.,Hiebl, B. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-3 %P 57-63 %R doi:10.3233/CH-2011-1395 %T Efficacy of CD14+ blood monocytes/macrophages isolation: Positive versus negative MACS™ protocol %U https://doi.org/10.3233/CH-2011-1395 1-3 %X Cardiovascular implants such as stents or artificial vascular grafts established in clinical application to date are generally designed as long-term implants. An important requirement for the successful application of these devices is the haemocompatibility of their interface to the blood stream, which often is approached by polymeric coatings. Modern therapies are aiming at curative treatments (Regenerative Medicine) by inducing the in vivo formation of a new endothelial layer on the implant surface ensuring an optimal haemocompatibility based on the generated glycocalyx. A promising approach for providing the required biological stimulus is the secretion of pro-angiogenic factors (such as VEGF-A) by autologous CD14+ monocytes/macrophages (mo/mΦ), which can be induced by previous angiogenic stimulation. While protocols for negative and positive immune-isolation are already established, this study was aimed to evaluate the efficacy of a positive and a negative MACS™ based immune-isolation protocol by analysing the yield, the purity and the activation status of the isolated CD14+ mo/mΦ. Both protocols enabled the isolation of more than 80% (positive isolation) and 86% (negative isolation) CD14+ mo/mΦ representing approximately 1.3 × 107 CD14+ mo/mΦ from 1 ml buffy coat. Less than 10% of these cells were also positive for CD69. Latter is an important selection criterion as CD69 is a marker characteristic for classically activated and catabolic active mo/mΦ which can negatively affect the endothelialisation process. As the negative immune-isolation protocol resulted in a cell fraction meeting the requirements on a pure cell fraction (percentage of contaminating cells < 15%) this isolation method is advantageous although it was more time consuming than the positive isolation protocol. %0 conference lecture %@ %A Jung, F.,Leithaeuser, B.,Franke, R.-P.,Mrowietz, C.,Pindur, G. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Correlation between postischemic vasodilation of the arteria brachialis and of the postischemic hyperemia in the adjacent microvascular bed %U %X %0 journal article %@ 1386-0291 %A Mayer, A.,Kratz, K.,Hiebl, B.,Lendlein, A.,Jung, F. %D 2011 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 423-430 %R doi:10.3233/CH-2011-1492 %T Support of HUVEC proliferation by pro-angiogenic intermediate CD163+ monocytes/macrophages: A co-culture experiment %U https://doi.org/10.3233/CH-2011-1492 1-4 %X So called intermediate (MO2) monocytes/macrophages possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic, acrylamide-based hydrogel human intermediate (CD14++ CD16+) CD163++ monocytes/macrophages (aMO2) which were angiogenically stimulated, maintained a pro-angiogenic and non-inflammatory status for at least 14 days. Here we explored, whether this aMO2 subset can positively influence the proliferation of human umbilical venous endothelial cells (HUVECs) without switching back into a pro-inflammatory (MO1) phenotype. aMO2 or HUVEC were seeded alone on glass cover slips (0.5 × 105 cells / 1.33 cm2) in a HUVEC specific cell culture medium (EGM-2) for 3 hrs, 24 hrs and 72 hrs or under co-culture conditions (0.5 × 105 HUVEC + 0.25 × 105 aMO2 / 1.33 cm2) in EGM-2 for the same time window as well (n = 6 each). Under co-culture conditions the numbers of adherent HUVEC per unit area were significantly higher (p < 0.01; 525 ± 52 HUVEC/mm2) compared to control mono-cultures (473 ± 76 HUVEC/mm2) after 72 hrs of cultivation and showed their typically spread morphology. The aMO2 remained in their subset status and secreted VEGF-A165 without release of pro-inflammatory cytokines until the end of the 72 hrs cultivation time period, thereby supporting the HUVEC proliferation. These in vitro results might indicate that this MO subset can be used as cellular delivery system for pro-angiogenic and non-inflammatory mediators to support the endothelialisation of biomaterials like e.g. cPnBA. %0 conference lecture %@ %A Franke, R.P.,Fuhrmann, R.,Mrowietz, C.,Hiebl, B.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Do radiographic contrast media (Iodixanol or Iomeprol) induce a perturbation of human arterial and/or venous endothial cells in vitro on extracellular matrix? %U %X %0 conference lecture %@ %A Leithaeuser, B.,Mrowietz, C.,Park, J.-W.,Jung, F. %D 2011 %J 16th International Conference of the European Society for Clinical Hemorheology and Microcirculation (ESCHM) and the 30th Annual Conference of the German Society for Clinical Microcirculation and Hemorheology (DGKMH) %N %P %T Influence of acetylsalicylic acid (Aspirin) on cutaneous microcirculation %U %X %0 journal article %@ 1042-7147 %A Cui, J.,Kratz, K.,Hiebl, B.,Jung, F.,Lendlein, A. %D 2011 %J Polymers for Advanced Technologies %N 1 %P 126-132 %R doi:10.1002/pat.1816 %T Soft poly(Eta-butyl acrylate) networks with tailored mechanical properties designed as substrates for in vitro models %U https://doi.org/10.1002/pat.1816 1 %X Mechanical conditioning can serve as a potent tool to influence mechano-responsive cells, which plays a prominent role during formation and regeneration of functional tissue. Recently, the differentiation of mesenchymal stem cells could be influenced by the local stiffness of hydrogels used as 2D substrates. However, the mechanical properties and the swellability of hydrogels in physiological liquids are difficult to control precisely as their properties strongly depend on physical parameters like ionic strength or pH value. Here, we explored amorphous, hydrophobic poly(n-butyl acrylate) networks (cPnBA) as soft substrates for cell culture system with adjustable mechanical properties. cPnBAs were synthesized via bulk radical polymerization from n-butyl acrylate (nBA) and poly(propylene glycol) dimethacrylate (PPGDMA) as crosslinker. The Young's modulus for cPnBAs determined by tensile tests could be systematically adjusted from 100 kPa to 10 MPa by increasing the PPGDMA-content at ambient temperature, while the glass transition temperature (Tg) was found to increase from −46 to −22°C. All cPnBAs exhibited similar surface properties with a surface roughness (Rq) in the range from 1.4 to 0.4 µm and advancing contact angles from 115° to 100°, which remained constant after ethylene oxide sterilization. The extracts of sterilized materials were tested for cytotoxic effects with L929 cells. All tested samples were non-cytotoxic. The functional integrity of cell membranes and mitochondrial activity stayed unaffected. The investigated polymer networks are promising candidates as soft substrates for passive mechanical stimulation of cells in vitro in cell culture devices or in vivo as implant coatings. %0 journal article %@ 1022-1360 %A Schneider, T.,Kohl, B.,Sauter, T.,Becker, T.,Kratz, K.,Schossig, M.,Hiebl, B.,Jung, F.,Lendlein, A.,Ertel, W.,Schulze-Tanzil, G. %D 2011 %J Macromolecular Symposia %N 1 %P 28-39 %R doi:10.1002/masy.201100057 %T Viability, adhesion and differentiated phenotype of articular chondrocytes on degradable polymers and electro-spun structures thereof %U https://doi.org/10.1002/masy.201100057 1 %X Degradable polymers are essential to enable biomaterial-based regenerative therapies, particularly, in articular cartilage defect healing, which remains a major clinical challenge. The aim of this study was to investigate the effect of two degradable polymers (as a film or scaffold) on primary articular chondrocytes vitality, adherence, differentiated phenotype and morphology. Films and electro-spun scaffolds were prepared from degradable poly(ether)ester urethane (PDC), which was synthesized via co-condensation of poly(p-dioxanone)diol and poly(ε-caprolactone)diol with an aliphatic diisocyanate and poly(p-dioxanone) (PPDO). The thermal and mechanical properties and the surface roughness of the films and scaffolds were examined by differential scanning calorimetry, dynamic mechanical thermal analysis, tensile tests and optical profilometry. Primary porcine articular chondrocytes were seeded on the polymers and analysed for viability, ultrastructure (scanning electron microscopy) and immunolabelled for type II collagen. All films and scaffolds exhibited a low endotoxin load < 0.06 EU/ml and only moderate cytotoxic effects when tested with L929 cells. The results of the seeding experiments revealed that survival and adhesion of chondrocytes depended strongly on seeding density. Vital chondrocytes could be detected on both PPDO and PDC films and scaffolds. They produced the cartilage-specific protein type II collagen indicating differentiated functions. However, they exhibited a mixed morphology on the films and a more flattened cell shape on the scaffolds. The cell/biomaterial interaction in the PPDO scaffolds or films was more intense compared to that in PDC topologies. %0 journal article %@ 0391-3988 %A Schneider, T.,Kohl, B.,Sauter, T.,Becker, T.,Kratz, K.,Schossig, M.,Jung, F.,Lendlein, A.,Ertel, W.,Schulze-Tanzil, G. %D 2011 %J The International Journal of Artificial Organs %N 8 %P 688 %R doi:10.5301/IJAO.2011.8702 %T Interaction of chondrocytes with electrospun polymer scaffolds depending on the fibre orientation %U https://doi.org/10.5301/IJAO.2011.8702 8 %X No abstract %0 journal article %@ 1022-1360 %A Roch, T.,Pierce, B.F.,Zaupa, A.,Jung, F.,Neffe, A.T.Lendlein, A. %D 2011 %J Macromolecular Symposia %N 1 %P 182-189 %R doi:10.1002/masy.201100048 %T Reducing the Endotoxin Burden of Desaminotyrosine- and Desaminotyrosyl tyrosine-Functionalized Gelatin %U https://doi.org/10.1002/masy.201100048 1 %X Biomaterial-induced autoregeneration requires materials with distinct tailored mechanical and thermal properties, water uptake and swelling properties as well as degradation behavior. Furthermore, before any biomaterial can be applied in vivo, in vitro studies should be performed that confirm the suitability for such applications. One facet in this process is the evaluation of endotoxin loads and immunogenic response to the material to avoid an unspecific activation of the immune system, which otherwise might cause fever and could lead to life–threatening pathologies. In this study, gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) were investigated in terms of their endotoxin content and their potential to induce an inflammatory cytokine response in macrophages. Using the Limulus amebocyte lysate (LAL) test it could be shown that the endotoxin content was substantially reduced by using certified low endotoxin containing gelatin and performing the gelatin functionalization under cleanroom conditions. Furthermore, production of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor–alpha (TNFα) of an immune relevant macrophage cell line was significantly reduced for these materials. The survival of the macrophage cell line in the presence of DAT(T)-functionalized gelatins was not influenced by both materials. Therefore, DAT- and DATT-functionalized gelatins were shown to have passed the tests concerning immunological responses important for their applicability in vivo. %0 conference lecture (invited) %@ %A Jung, F.,Lendlein, A. %D 2011 %J 25. Sitzung des Ausschusses fuer Wissenschaft, Forschung und Kultur %N %P %T Ausseruniversitaere Forschungseinrichtungen in Brandenburg – Zusammenarbeit mit Wirtschaft und Hochschulen %U %X %0 conference lecture %@ %A Jung, F.,Neffe, A.T.,Lendlein, A. %D 2011 %J 38th Congress of the European Society for Artificial Organs, ESAO 2011 %N %P %T Hemocompatibility Testing of Polymers and Hemo-/Histocompatible Polymers %U %X %0 journal article %@ 1076-3279 %A Cui, J.,Kratz, K.,Hiebl, B.,Jung, F.,Lendlein, A. %D 2011 %J Tissue Engineering A %N 3-4 %P 531-584 %R doi:10.1089/ten.tea.2010.1502 %T Poly(n-butyl acrylate) networks with tailored mechanical properties designed as model substrates for mechano-responsive cells %U https://doi.org/10.1089/ten.tea.2010.1502 3-4 %X No abstract %0 journal article %@ 0026-2862 %A Hiebl, B.,Mrowietz, C.,Lee, S.,Braune, S.,Knaut, M.,Lendlein, A.,Franke, R.P.,Jung, F. %D 2011 %J Microvascular Research %N 1 %P 52-57 %R doi:10.1016/j.mvr.2011.04.001 %T Influence of polymeric microspheres on the myocardial oxygen partial pressure in the beating heart of pigs %U https://doi.org/10.1016/j.mvr.2011.04.001 1 %X Injection of labeled microspheres is an established method in animal models to analyze the capillary organ blood flow at different time points. However, the microspheres can lead to stenoses of the capillary lumen, which might affect tissue oxygen supply.,Our study aimed to investigate the influence of repeated injections of microspheres into the left coronary artery on the tissue oxygen partial pressure (pO2) in the downstream supplied myocardium of Göttingen minipigs. Tests (n = 6 pigs each) were performed with two differently sized microspheres (ø = 10 ± 0.1 μm (M10) or ø = 15 ± 0.15 μm (M15)) from polystyrene. The pO2 was measured in the midmyocardium of the left and right ventricle for 6 min continuously after each of five injections (1 × 106 microspheres each). There was a time laps of 12 min between each injection. In addition, the influence of the carrier solution was analyzed solely in the identical time frame.,pO2 decreased significantly in the myocardial area supplied by the ramus interventricularis paraconalis after injection of M15 microspheres. In contrast, the application of the M10 microspheres did not change the myocardial pO2. This finding suggests to use microspheres with diameters not exceeding 10 μm for the coronary blood flow assessment. %0 conference poster %@ %A Schneider, T.,Kohl, B.,Sauter, T.,Becker, T.,Kratz, K.,Schossig, M.,Jung, F.,Lendlein, A.,Ertel, W.,Schulze-Tanzil, G. %D 2011 %J 38th Congress of the European Society for Artificial Organs, ESAO 2011 %N %P %T Interaction of chondrocytes with electrospun polymer scaffolds depending on the fibre orientation %U %X %0 journal article %@ 1386-0291 %A Hiebl, B.,Mrowietz, C.,Goers, J.,Bahramsoltani, M.,Plendl, J.,Kratz, K.,Lendlein, A.,Jung, F. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-3 %P 233-238 %R doi:10.3233/CH-2010-1350 %T In vivo evaluation of the angiogenic effects of the multiblock copolymer PDC using the hen's egg chorioallantoic membrane test %U https://doi.org/10.3233/CH-2010-1350 2-3 %X Multiblock copolymers with shape-memory capability attracted tremendous interest as promising candidate materials for smart, degradable implants. In the present study the hen's egg-chorioallantoic membrane test (HET-CAM test) was used to investigate the angiogenic properties of a thermoplastic, biodegradable multiblock copolymer PDC composed of poly(p-dioxanone) hard segments (PPDO) and crystallizable poly(ε-caprolactone) switching segments (PCL), whereby PPDO and PCL homopolymers were investigated as controls. According to our HET-CAM test data, only PDC induced significant microvessel attraction and formation in the contact area of the test specimen after 48hours of incubation showing newly formed blood vessels along the outer edge of the material. In contrast, no newly formed blood vessels were observed around the PPDO or PCL specimen after the same incubation period. These in vivo results indicate that the multiblock copolymer PDC possibly possesses an angiogenic effect and it can induce blood vessel formation in its direct vicinity when it is implanted in vivo. %0 journal article %@ 1386-0291 %A Hiebl, B.,Fuhrmann, R.,Jung, F.,Kratz, K.,Lendlein, A.,Franke, R.-P. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 117-122 %R doi:10.3233/CH-2010-1289 %T Degradation of and angiogenesis around multiblock copolymers containing poly(Rho-dioxanone)- and poly(Epsilon-caprolactone)-segments subcutaneously implanted in the rat neck %U https://doi.org/10.3233/CH-2010-1289 2-4 %X The degradation behavior and the effect on angiogenesis of multiblock copolymers based on poly(p-dioxanone)- and poly(ε-caprolactone)-segments (PDC) were studied in vivo. PDC is a multifunctional biomaterial combining degradability and shape-memory capabilities. The “in vivo” degradation of PDC is characterized by a fragmentation occurring at the material tissue interface. This observation is consistent with the enzyme supported degradation behaviour, which was determined “in vitro”. PDC revealed to induce the formation of blood micro-vessels nearby in the periimplantary tissues. Both might explain the good PDC integration into tissues in terms of a strong connection between the implant and the periimplantary tissue. Micro blood-vessels might be involved in the clearance of the small particles, which appear in the periimplantary tissue when PDC degrades. %0 journal article %@ 1386-0291 %A Franke, R.P.,Minkow, A.,Hiebl, B.,Fuhrmann, R.,Mrowietz, C.,Jung, F. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-3 %P 225-232 %R doi:10.3233/CH-2010-1349 %T Embedding of radiographic media molecules in the membrane of erythrocytes %U https://doi.org/10.3233/CH-2010-1349 2-3 %X The incubation of erythrocytes (RBC) or endothelial cells (HUVEC) in radiographic contrast media (RCM) could induce morphological alterations of or at the cell membranes, e.g. the generation of echinocytes or the formation of stress fibres coinciding with a massive buckling of HUVEC into the vascular lumen, as was demonstrated in several examinations in the recent years. The apposition or embedding of RCM at or in the cell membranes was discussed as possible causative mechanisms because the embedding of molecules into the internal leaflet of the cell membrane bilayer is expected to bulge the cell membrane to the outside, thus inducing e.g. the generation of echinocytes. The examination presented here is based therefore on high resolution scanning electron microscopy (SEM) analyses if iodine as marker element of RCM molecules can be found near the inside of or in RBC membranes (co-localisation study). Morphological analyses exploited secondary electron images (SE) while the analysis of elements exploited either back scattered electrons (BSE) or energy dispersive X-ray analysis (EDX) or the areal display of elements in high lateral resolution in the Bit-map modus. Even at the highest convenient magnification (1:40,000) it was impossible to detect RBC membrane associated iodine (I) after RBC incubation in RCM (Iodixanol, Iopromide) in vitro. Neither in the birds view on the samples nor looking from the side on the freeze fractured samples carrying the RBC was it possible to detect either the signal cohorts typical of I in the sum spectra or the main Lα1-peak in trace analysis. %0 journal article %@ 0168-1656 %A Hiebl, B.,Luetzow, K.,Lange, M.,Jung, F.,Seifert, B.,Klein, f.,Weigel, T.,Kratz, K.,Lendlein, A. %D 2010 %J Journal of Biotechnology %N 1 %P 76-82 %R doi:10.1016/j.jbiotec.2010.01.006 %T Cytocompatibility testings using cell culture modules fabricated from specific candidate biomaterials using injection molding %U https://doi.org/10.1016/j.jbiotec.2010.01.006 1 %X Most polymers used in clinical applications today are materials that have been developed originally for application areas other than biomedicine. Testing the cell- and tissue-compatibility of novel materials in vitro and in vivo is of key importance for the approval of medical devices and is regulated according to the Council Directive 93/42 of the European communities concerning medical devices. In the standardized testing methods the testing sample is placed in commercially available cell culture plates, which are often made from polystyrene. Thus not only the testing sample itself influences cell behavior but also the culture vessel material. In order to exclude this influence, a new system for cell testing will be presented allowing a more precise and systematic investigation by preparing tailored inserts which are made of the testing material. Inserts prepared from polystyrene, polycarbonate and poly(ether imide) were tested for their cytotoxity and cell adherence. Furthermore a proof of principle concerning the preparation of inserts with a membrane-like surface structure and its surface modification was established. Physicochemical investigations revealed a similar morphology and showed to be very similar to the findings to analogous preparations and modifications of flat-sheet membranes. %0 journal article %@ 0026-2862 %A Hiebl, B.,Mrowietz, C.,Ploetze, K.,Matschke, K.,Jung, F. %D 2010 %J Microvascular Research %N 3 %P 389-393 %R doi:10.1016/j.mvr.2010.06.002 %T Critical hematocrit and oxygen partial pressure in the beating heart of pigs %U https://doi.org/10.1016/j.mvr.2010.06.002 3 %X In cardiac surgery the substitution of lost blood volume by plasma substitutes is a common therapeutical approach. None of the currently available blood substitutes has a sufficient oxygen transport capacity. This can limit the functional integrity of the myocardium known as highly oxygen consumptive. The study was aimed to get information about the minimal hematocrit, also known as critical hematocrit (cHct), which guarantees a stable and adequate oxygen partial pressure in the myocardium (pO2). In adult female pigs (n = 7) the hematocrit was reduced by isovolemic blood dilution with an intravenous infusion of isotonic 4% gelatine polysuccinate solution, The substituted blood volume ranged between 3000 ml and 7780 ml (mean: 5254 ± 1672 ml). In all animals the pO2 of the myocardium of the beating heart and of the resting skeletal muscle increased until blood dilution resulted in a Hct decrease down to 15%. Further blood dilution resulted in a decrease of the pO2. Only after the Hct was < 10% the pO2 was lower than before blood dilution and accompanied by a lethal ischemia of the myocardium. These data indicate a cHct of about 10% in the pig animal model. %0 journal article %@ 1386-0291 %A Jung, F. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 79-99 %R doi:10.3233/CH-2010-1312 %T From hemorheology to microcirculation and regenerative medicine: Fahraeus Lecture 2009 %U https://doi.org/10.3233/CH-2010-1312 2-4 %X No abstract %0 journal article %@ 0883-7694 %A Jung, F.,Wischke, C.,Lendlein, A. %D 2010 %J MRS Bulletin %N 8 %P 607-613 %T Degradable, Multifunctional Cardiovascular Implants: Challenges and Hurdles %U 8 %X Polymer-coated and polymer-based cardiovascular implants are essential constituents of modern medicine and will proceed to gain importance with the demographic changes toward a society of increasing age-related morbidity. Based on the experiences with implants such as coronary or peripheral stents, which are presently widely used in clinical medicine, several properties of the next generation of cardiovascular implants have been envisioned that could be fulfilled by multifunctional polymers. The challenge is to combine tailored mechanical properties and rapid endothelialization with controlled drug release in order to modulate environmental cells and tissue. Additionally, degradability and sensitivity to external stimuli are useful in several applications. A critical function in terms of clinical complications is the hemocompatibility. The design of devices with improved hemocompatibility requires advanced in vitro test setups as discussed in depth in this article. Finally, degradable, multifunctional shape-memory polymers are introduced as a promising family of functional polymers that fulfill several requirements of modern implants and are of high relevance for cardiovascular application (e.g., stent technology). Such multifunctional polymers are a technology platform for future cardiovascular implants enabling induced autoregeneration in regenerative therapies. %0 journal article %@ 1386-0291 %A Hiebl, B.,Jung, F.,Schossig, M.,Scharnagl, N.,Richau, K.,Niehues, S. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 347-358 %R doi:10.3233/CH-2010-1313 %T In vitro evaluation of a nitinol based vein cuff for external valvuloplasty %U https://doi.org/10.3233/CH-2010-1313 2-4 %X This study shows first in vitro tests of a nitinol based vein cuff developed for external valvuloplasty. In contrary to currently existing vein cuffs the tested model enables minimal invasive implantation and also maintains its round pre-shaped profile at body temperature (37°C). The examination of the cuff surface structure by scanning electron microscopy, profilometry and X-ray photoelectron spectroscopy after sterilization with ethylene oxide and before cyto-compatibility testing revealed a nearly smooth surface (mean square roughness Rq 66 ± 33 nm) which was primarily composed of nickel, oxygen, titanium, carbon and silicon where nickel was the least fraction (Ni: 0.7%, Ti: 1.7%, Si: 15.8%, O: 29.5%, C: 52.3%) of the surface elements. Si and C are supposed to be contaminations caused by a final cuff polishing with silicon carbide at the end of the manufacturing process. To evaluate cyto-compatibility initial cell adherence and cell activity were assessed. The results showed good initial cell adherence of L929 fibroblast-like cells on the cuff surface already after 24 h. The results also revealed no inhibitory effects on the activity of these cells (MTS test) later on. The test setup developed to analyse functionality in a dynamic mode was shown to be suited at blood pressures up to 300 mmHg. The cuff successfully limited dilation of varicose veins (Vena saphena magna) at physiological blood pressures (< 120 mmHg) and also in cases of hypertonia (300 mmHg) to the diameter determined by the cuff (4.0 mm) over thecomplete testing period. This indicates that the clasp based cuff closure mechanism is suited to close the cuff under variable physiological and pathological blood pressure conditions. The cuff structure only allowed minimal adaptation on the inhomogenously dilating vein profile in the both peripheral cuff modules. Both peripheral modules followed the vessel dilation in correlation to the applied pressure. At pressures within the physiological range ≤ 120 mmHg) the variation of the lateral arch module diameter was only marginal, whereas at 300 mmHg pressure the peripheral modules followed vein dilation up to a diameter of 5.0 to 5.5 mm. The cuff also maintained the pre-shaped round profile in the central and peripheral modules during the pressure increase and the consecutive cuff expansion. The study showed that the first nitinol based vein cuff for external valvuloplasty was processed well enough by electropolishing and sterilization to allow culturing of L929 fibroblast-like cells on the cuff surface as a test of general biocompatibility. The cuff also proved to limit dilation of varicose veins at physiological and pathological blood pressures in vitro. Further tests with primary cells from the venous wall will follow to test the specific biocompatibility before tests in vivo can be envisaged. %0 journal article %@ 1313-2458 %A Seifert, B.,Hiebl, B.,Jung, F. %D 2010 %J Series on BIOMECHANICS %N 1-2 %P 140-146 %T Interaction of platelets with body foreign surfaces %U 1-2 %X Medical devices in contact with blood have to be haemocompatible. In vivo haemocompatibility is mediated by the glycocalix ofthe endothelial cells lining the wall ofthe blood vessel. 1fthis lining is injured or a foreign surface is implanted the blood contacts the sub-endotheliallayers ofthe vessel wall/body foreign surface and adhere there. This adhesion leads to the activation ofblood cells, mainly of platelets (thrombocytes), vasoconstriction and the release oftissue fuctor. This release triggers the activation ofplasmatic coagulation. The main role in these processes plays the activation ofplatelets. Methods for evaluation and prevention of activation of platelets on foreign body surfaces are presented. %0 journal article %@ 1386-0291 %A Cui, J.,Trescher, K.,Kratz, K.,Jung, F.,Hiebl, B.,Lendlein, A. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 401-411 %R doi:10.3233/CH-2010-1322 %T Melt-processable hydrophobic acrylonitrile-based copolymer systems with adjustable elastic properties designed for biomedical applications %U https://doi.org/10.3233/CH-2010-1322 2-4 %X Acrylonitrile-based polymer systems (PAN) are comprehensively explored as versatile biomaterials having various potential biomedical applications, such as membranes for extra corporal devices or matrixes for guided skin reconstruction. The surface properties (e.g. hydrophilicity or charges) of such materials can be tailored over a wide range by variation of molecular parameters such as different co-monomers or their sequence structure. Some of these materials show interesting biofunctionalities such as capability for selective cell cultivation. So far, the majority of AN-based copolymers, which were investigated in physiological environments, were processed from the solution (e.g. membranes), as these materials are thermo-sensitive and might degrade when heated. In this work we aimed at the synthesis of hydrophobic, melt-processable AN-based copolymers with adjustable elastic properties for preparation of model scaffolds with controlled pore geometry and size. For this purpose a series of copolymers from acrylonitrile and n-butyl acrylate (nBA) was synthesized via free radical copolymerisation technique. The content of nBA in the copolymer varied from 45 wt% to 70 wt%, which was confirmed by 1H-NMR spectroscopy. The glass transition temperatures (Tg) of the P(AN-co-nBA) copolymers determined by differential scanning calorimetry (DSC) decreased from 58°C to 20°C with increasing nBA-content, which was in excellent agreement with the prediction of the Gordon-Taylor equation based on the Tgs of the homopolymers. The Young’s modulus obtained in tensile tests was found to decrease significantly with rising nBA-content from 1062 MPa to 1.2 MPa. All copolymers could be successfully processed from the melt with processing temperatures ranging from 50°C to 170°C, whereby thermally induced decomposition was only observed at temperatures higher than 320°C in thermal gravimetric analysis (TGA). Finally, the melt processed P(AN-co-nBA) biomaterials were sterilized with ethylene oxide and tested for cytotoxicity in direct contact tests with L929 cells according to the EN DIN ISO standard 10993-5. All tested samples exhibited non-toxic effects on the functional integrity of the cell membrane and the mitochondrial activity. However, the morphology of the cells on the samples was different from that observed on polystyrene as control, indicating slightly cytotoxic effects according to the evaluation guide of the US Pharmacopeial Convention. Thus, the melt-processable, hydrophobic P(AN-co-nBA) copolymers with adjustable mechanical properties are promising candidates for in vitro investigations of tissue growth kinetics. %0 journal article %@ 1386-0291 %A Franke, R.-P.,Fuhrmann, R.,Mrowietz, C.,Rickert, D.,Hiebl, B.,Jung, F. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 123-130 %R doi:http://dx.doi.org10.3233/CH-2010-1290 %T Reduced diagnostic value of lactate dehydrogenase (LDH) in the presence of radiographic contrast media %U https://doi.org/http://dx.doi.org10.3233/CH-2010-1290 2-4 %X Isoforms of the enzyme lactate dehydrogenase (LDH) were found in almost all cells of the organism and an elevated activity of LDH in the circulation is thought to be a clear indicator of elevated cell destruction coinciding with an increased release of components from the cellular cytoplasm, e.g. LDH. Here, we report on an in-vitro examination to test whether radiographic contrast media (RCM) could induce cell destruction followed by an increase in LDH release. The RCM were tested in non-flow cultures of human umbilical venous endothelial cells (HUVEC) of the fourth passage seeded on extracellular matrix and the results were compared to those from control cultures not exposed to contrast media. The examination revealed that the addition of contrast media to the cell culture media supplemented with pooled human serum (HSP) as source of exogenous LDH was followed by a strong decrease in LDH activity both in the absence and presence of HUVEC. Within 1.5 min after the addition of contrast media to the culture medium supplemented with HSP (30% vol of the culture medium were replaced by either of two contrast media, Iodixanol or Iopromide) the LDH activity decreased about 80% compared to the initial values. In contrast, the LDH activity did not change in cell culture media not supplemented with RCM. The partial replacement of HSP supplemented cell culture medium by RCM will cause a dilution of cell culture medium constituents. The decrease of LDH activity, however, was much stronger than the decrease thought to be attributable to the effects of dilution of cell culture medium, so that the role of dilution seems to be a minor one in this case. It has to be assumed that the RCM could interact with the LDH available in the culture medium as well as with the substrates delivered with the measurement system for the assessment of LDH activity, so that both, the amount of LDH and the activities of enzymes involved might be influenced. In the presence of HUVEC a similar effect was observed. Here, a little less strong decrease of LDH activity occurred compared to the decrease in cell culture medium without HUVEC. This was unexpected because a considerable amount of HUVEC were detached after the addition of contrast media and many of these cells were damaged seriously so that a significant amount of endogenous LDH should have been released. These unexpected results make it necessary to re-evaluate those past time examinations focussed on cell damage/destruction in the presence of contrast media, where the measurement of LDH activity was used as indicator or cell vitality and where cell decease rates were correlated to questionable toxic influences. According to the results of the examination reported here it is difficult to uphold the interpretation of recently published findings that contrast media almost exclusively induce cellular apoptosis and not necrosis. %0 journal article %@ 1386-0291 %A Mayer, A.,Lee, S.,Jung, F.,Gruetz, G.,Lendlein, A.,Hiebl, B. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-3 %P 217-223 %R doi:10.3233/CH-2010-1348 %T CD14+ CD163+ IL-10+ monocytes/macrophages: Pro-angiogenic and non pro-inflammatory isolation, enrichment and long-term secretion profile %U https://doi.org/10.3233/CH-2010-1348 2-3 %X The establishment of a stable endothelial layer on a biomaterial suture is a well known strategy to achieve hemocompatibility. The endothelialisation is supported by factors as e.g. vascular endothelial growth factor (VEGF), which can be secreted by monocytes/macrophages (mo/mΦ) in an angiogenic milieu. In order to avoid detrimental inflammation triggered by these mo/mΦ, we established a protocol for the generation of alternatively activated macrophages and studied their response towards VEGF-A165. We could generate sufficient amounts of these CD14+ CD163+ IL-10+ mo/mΦ from buffy coats(8.6 ± 4.7 × 105 cells/mlbuffy coat). Furthermore, we achieved a VEGF-A165 secretion in the nanogram range. The VEGF-A165 secretion increased 2.1-fold within 14 days from 7.6 ± 2.2 to 16.1 ± 2.5ng/ml when the cells were grown with a VEGF-A165 supplemented (10ng/ml) cell culture medium. Within this time period the secretion levels of other pro-angiogenic growth factors (bFGF, PDGF-BB) and immunomodulatory cytokines (IL-10, IL-12, IL-1ra, TNFα, IFNγ) reached only the picogram range. These results suggest that angiogenically stimulated CD14+ CD163+ IL-10+ mo/mΦ might be useful as a cellular cytokine delivery system supporting endothelialisation of biomaterials without inducing pro-inflammatory effects. %0 journal article %@ 1386-0291 %A Leithaeuser, B.,Jung, F.,Park, J.-W. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-4 %P 311-323 %R doi:10.3233/CH-2010-1314 %T Rheological and hemostasiological aspects of thrombus formation in the left atrial appendage in atrial fibrillation? A new strategy for prevention of cardioembolic stroke %U https://doi.org/10.3233/CH-2010-1314 2-4 %X Atrial fibrillation (AF), as the most common cardiac rhythm disturbance, gains in importance not only for the persons affected, but also for health care and social economy due to thromboembolic events, of which stroke is the most serious, disabling, and life threatening one. Cardiac embolism is due to thrombus formation mainly in the left atrial appendage (LAA). The pathophysiology leading to increased thrombogenicity is complex and requires a remodelling of the LAA structure, decreased LAA blood flow, activation of inflammatory processes, deviations of the hemostatic/fibrinolytic system, and activation/dysfunction of endothelial/endocardial cells. Altogether, a prothrombotic state proposed by Virchow more than 150 years ago. The presence of a LAA thrombus, therefore, is a result of a dynamic process of clot formation and lysis. A comprehensive understanding of this pathophysiology is helpful to optimize the management of patients at high risk of cardioembolic stroke. Especially those with contraindications for oral anticoagulation are in a need of an alternative approach that is not associated with a long-term risk of hemorrhage and other attendant circumstances. The reasonable alternative may be the exclusion of the LAA cavity from circulation by either surgical or percutaneous catheter-based procedures. %0 journal article %@ 1386-0291 %A Hiebl, B.,Bog, S.,Mrowietz, C.,Juenger, M.,Jung, F.,Lendlein, A.,Franke, R.P. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-3 %P 211-216 %R doi:10.3233/CH-2010-1347 %T Influence of VEGF stimulated human macrophages on the proliferation of dermal microvascular endothelial cells: Coculture experiments %U https://doi.org/10.3233/CH-2010-1347 2-3 %X Monocytes/macrophages are known to exhibit pro-angiogenic activities after VEGF stimulation. Recently, it was shown that VEGF stimulated macrophages can support growth of microvascular endothelial cells from the lung when both cell types were cocultured using a cell ratio of 1:1. However, endothelial cells can have different phenotypic characteristics and metabolism depending on the originating vascular bed and tissues, and only few data have been published regarding the regiospecific sensitivity of microvascular endothelial cells for angiogenic stimuli. Reports about differences in the microvascular bed of the lung and the skin motivated to investigate angiogenic effects of VEGF stimulated macrophages (mΦa) on the doubling time and the cell growth behaviour of skin derived microvascular endothelial cells (HMVEC/S). During the study period of 60 days, mΦa supported growth and proliferation of the HMVEC/S, when mΦa and HMVEC/S were cocultured at a ratio of 0.5:1. However, these effects were not seen in a 1:1 coculture. This result indicates that there is a positive correlation between the pro-angiogenic effects of mΦa and the number of endothelial cells in the direct neighbourhood of the mΦa and also suggests a different sensitivity of microvascular endothelial cells to angiogenic stimuli depending on the tissue from which they were isolated. %0 journal article %@ 1386-0291 %A Braune, S.,Lange, M.,Richau, K.,Luetzow, K.,Weigel, T.,Jung, F.,Lendlein, A. %D 2010 %J Clinical Hemorheology and Microcirculation %N 2-3 %P 239-250 %R doi:10.3233/CH-2010-1351 %T Interaction of thrombocytes with poly(ether imide): The influence of processing %U https://doi.org/10.3233/CH-2010-1351 2-3 %X The processing of polymers for blood contacting devices can have a major influence on surface properties. In this study, we fabricated poly(ether imide) (PEI) membranes and films to investigate the effects of the processing on physicochemical surface properties by atomic force microscopy (AFM), scanning electron microscopy, contact angle as well as zeta potential measurements. A static platelet adhesion test was performed to analyze the thrombogenicity of both devices. While contact angle measurements showed similar levels of hydrophobicity and zeta potential values were equivalent, mean surface roughness as well as surface energies in the dispersive part were found to be increased for the PEI membrane. The static platelet adhesion test showed a significantly decreased number of adherent platelets per surface area on the PEI film (178.98 ± 102.70/45000 μm2) compared to the PEI membrane (504 ± 314.27/45000μm2) and, consequently, revealed evidence for higher thrombogenicity of the PEI membrane. This study shows that processing can have a significant effect on platelet adhesion to biomaterials, even though, molar weight was identical. Thrombogenicity of polymer-based cardiovascular devices, therefore, have to be evaluated at the final product level, following the entire processing procedure. %0 journal article %@ 1313-2458 %A Hiebl, B.,Kratz, K.,Fuhrmann, R.,Jung, F.,Lendlein, A.,Franke, R.-P. %D 2010 %J Series on BIOMECHANICS %N 3-4 %P 61-65 %T Changes in the subcutaneous tissue and the chorioallantois membrane of eggs caused by poly(p-dioxanone)- and poly(ε- caprolactone) multiblock copolymers %U 3-4 %X %0 conference lecture %@ %A Wischke, C.,Krueger, A.,Roch, T.,Pierce, B.F.,Li, W.,Jung, F.,Lendlein, A. %D 2010 %J 8th International Conference and Workshop on Biological Barriers - In vitro Tools in Nanotoxicology and Nanomedicine %N %P %T Endothelial cell response to (co)polymer nanoparticles depending on the inflammatory environment and comonomer ratio %U %X %0 conference poster %@ %A Cui, J.,Kratz, K.,Hiebl, B.,Jung, F.,Lendlein, A. %D 2010 %J 4th Congress on Regenerative Biology and Medicine, BioStar 2010 %N %P %T Poly(n-butyl acrylate) networks with tailored mechanical properties designed as model substrates for mechano-responsive cells %U %X %0 conference lecture %@ %A Franke, R.-P.,Fuhrmann, R.,Mrowietz, C.,Rickert, D.,Hiebl, B.,Jung, F. %D 2009 %J 28. Jahrestagung der Deustchen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Einfluss von Roentgenkontrastmittel auf die Ischaemiedetektion mittels Lactatdehydrogenase %U %X %0 conference lecture %@ %A Lee, S.,Ganesan, R.,Braune, S.,Kratz, K.,Lendlein, A.,Jung, F. %D 2009 %J 28. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Big ET-1 derived peptides enhances endothelial cell shear resistancy %U %X %0 conference poster %@ %A Mrowietz, C.,Hiebl, B.,Goers, J.,Bahramsoltani, M.,Plendl, J.,Kratz, K.,Lendlein, A.,Jung, F. %D 2009 %J 28. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T In vitro testing of angiogenic effects derived from polymer based biomaterials using the Hen’s egg test-chorioallantoic membrane method %U %X %0 conference lecture %@ %A Hiebl, B.,Mueller, C.,Bahramsoltani, M.,Plendl, J.,Jung, F.,Niehues, S. %D 2009 %J 28. Jahrestagung der Deustchen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Macro- and micromorphological studies of the vascular structures from the Goettingen® minipig %U %X %0 conference lecture %@ %A Hiebl, B.,Mrowietz, C.,Mayer, A.,Braune, S.,Franke, R.-P.,Jung, F. %D 2009 %J 28. Jahrestagung der Deustchen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Influence of microspheres on the myocardial partial oxygen pressure in the beating heart of pigs %U %X %0 conference lecture %@ %A Hiebl, B.,Fuhrmann, R.,Jung, F.,Kelch, S.,Lendlein, A.,Franke, R.-P. %D 2009 %J 28. Jahrestagung der Deustchen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Degradation of and angiogenesis around multiblock copolymers based on poly(Rho-dioxanone)/poly(Epsilon-caprolactone) subcutaneously implanted in the rat neck %U %X %0 conference poster %@ %A Braune, S.,Lange, M.,Luetzow, K.,Jung, F.,Haag, R.,Lendlein, A. %D 2009 %J 28. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Interaction of thrombocytes with poly(ether imide): the influence of processing %U %X %0 conference lecture %@ %A Hiebl, B.,Hamm, B.,Mueller, C.,Plendl, J.,Huenigen, H.,Jung, F.,Niehues, S. %D 2009 %J 28. Jahrestagung der Deustchen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T CT based studies of a nitinol vein cuff in minipigs: patency and stability %U %X %0 conference lecture %@ %A Leithaeuser, B.,Mrowietz, C.,Pindur, G.,Stermitzky, R.,Jung, F. %D 2009 %J 53. Jahrestagung der Gesellschaft fuer Thrombose und Haemostase %N %P %T Capillary bleeding under oral anticoagulation %U %X %0 conference paper %@ %A Hiebl, B.,Rickert, D.,Fuhrmann, R.,Jung, F.,Lendlein, A.,Franke, R.-P. %D 2009 %J Advances in Material Design for Regenerative Medicine, Drug Delivery, and Targeting/Imaging, MRS Symposium Proceedings, MRS Fall Meeting 2008 %N %P HH10-04 %R doi:10.1557/PROC-1140-HH10-04 %T Tissue Integration of Two Different Shape-Memory Polymers with Poly(e-Caprolactone) Switching Segment in Rats %U https://doi.org/10.1557/PROC-1140-HH10-04 %X %0 conference lecture %@ %A Wickersheim, A.,Franke, R.-P.,Jung, F.,Lee, S.,Hiebl, B. %D 2009 %J 15th Conference of the European Society of Clinical Hemorheology and Microcirculation %N %P %T Mid-term secretion profile of angiogenically stimulated CD14+ type II monocytes/macrophages %U %X %0 journal article %@ 0026-2862 %A Jung, F.,Franke, R.-P. %D 2009 %J Microvascular Research %N 2 %P 241-245 %R doi:10.1016/j.mvr.2009.02.010 %T Extreme reduction of the capillary lumen in segments of the venular legs of human cutaneous capillaries %U https://doi.org/10.1016/j.mvr.2009.02.010 2 %X While structure and function of precapillary sphincter cells were assured in skin capillaries it is unclear whether segmental reduction of capillary lumina can occur in human capillaries. It has been shown that endothelial cells are able to exert dynamical reactions. Since the first description of the vascular endothelium a great variety of findings were described concerning the active role of capillary endothelial cells in regulation of the capillary lumen applying intravital microscopy.,The intravital microscopy was performed in the framework of an observational study to document the long-term stability of capillaries in healthy subjects over many years. In the second year one of the participants showed remarkable changes in capillaries compared to recent recordings. Control recordings were performed 1, 3, 4, 5 and 20 h after the initial examination — until a complete normalization of the capillaries occurred.,This case report is documenting for the first time clearly that extreme luminal narrowing of long segments of cutaneous capillaries can also appear in humans, in this case restricted exclusively to the venular leg of the capillaries. Different from the reductions of the capillary lumen induced by electrical irritation in frogs which lasted only for seconds, the capillary lumen narrowing in this case lasted considerably longer, almost over a whole day.,It is important to note that the demonstrated findings did not occur in all capillaries and it remains unclear whether such findings are restricted to skin capillaries or might occur also in other regions of the body or even systemically. It could be demonstrated clearly, however, that segmental narrowing of capillary lumina can occur in humans possibly leading to a temporary stillstand of perfusion. %0 journal article %@ 1386-0291 %A Hoepken, S.,Fuhrmann, R.,Jung, F.,Franke, R.P. %D 2009 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 157-166 %R doi:10.3233/CH-2009-1230 %T Shear resistance of human umbilical endothelial cells on different materials covered with or without extracellular matrix: Controlled in-vitro study %U https://doi.org/10.3233/CH-2009-1230 1-2 %X A variety of medical grade polymeric materials are used in tissue engineering and biomedical technology. Dense non-porous polymeric foils were used as substrates for endothelial cell layers. Half a the test samples (polymers and control materials) were seeded with bovine corneal endothelial cells (BCEC) which more or less covered the substrates with an extracellular matrix (ECM) in the consecutive culturing period. Afterwards the ECM covered as well as the uncovered materials were seeded with human umbilical venous endothelial cells (HUVEC). HUVEC seeded samples were cultured either under static or under dynamical conditions in a cone/plate rheometer with a mean low arterial shear stress of 8.2 dyn/cm2 to simulate the flow conditions in a coronary vein graft.,With the exemption of polyvinyl chloride all other materials could be coated with ECM at least partially. Under static conditions the best results with respect to complete coverage with ECM and HUVEC were seen on polyester and polyurethane. Under shear load, however, the complete HUVEC layer together with the ECM detached from the polymer surface within a short time. ECM and HUVEC remained no longer than 43 minutes on anyone of the materials tested. The materials as supplied and tested were clearly not appropriate as implants in contact to the flowing blood. %0 journal article %@ 0008-6312 %A Park, J.-W.,Gerk, U.,Franke, R.-P.,Jung, F. %D 2009 %J Cardiology %N 3 %P 205-208 %R doi:10.1159/000149574 %T Post-Mortem Analysis of a Left Atrial Appendage Occlusion Device (PLAATO TM) in a Patient with Permanent Atrial Fibrillation %U https://doi.org/10.1159/000149574 3 %X No abstract %0 journal article %@ 0887-624X %A Choi, J.-H.,Ganesan, R.,Kim, D.-K.,Jung, C.-H.,Hwang, I.-T.,Nho, Y.-C.,Yun, J.-M.,Kim, J.-B. %D 2009 %J Journal of Polymer Science A %N 22 %P 6124-6134 %R doi:10.1002/pola.23655 %T Patterned immobilization of biomolecules by using ion irradiation-induced graft polymerization %U https://doi.org/10.1002/pola.23655 22 %X An efficient method for biomolecular patterning based on ion irradiation-induced graft polymerization has been demonstrated. Ion irradiation resulted in the formation of active species on the polymer surface, which in turn was utilized for graft polymerization of acrylic acid. Polymerization conditions were optimized to yield maximum grafting degree of poly(acrylic acid) onto the PTFE. The application of this platform for biomolecular patterning has been successfully demonstrated by patterning DNA and streptavidin on the poly(acrylic acid)-grafted PTFE substrates. This method is capable of grafting various functional groups such as amide and alcohol onto a variety of polymer substrates. %0 journal article %@ 0969-806X %A Choi, J.-H.,Jung, C.-H.,Kim, D.-K.,Suh, D.-H.,Nho, Y.-C.,Kang, P.-H.,Ganesan, R. %D 2009 %J Radiation Physics and Chemistry %N 7-8 %P 517-520 %R doi:10.1016/j.radphyschem.2009.03.037 %T Preparation of polymer/POSS nanocomposites by radiation processing %U https://doi.org/10.1016/j.radphyschem.2009.03.037 7-8 %X Multifunctional polyhedral oligomeric silsesquioxane (POSS)-reinforced polypropylene (PP) nanocomposites were prepared by a simple and economical radiation processing, which has a great potential for the preparation of high-performance materials. The tensile strength of PP/POSS nanocomposites increased with an increasing POSS content up to 5 wt% and with an increasing absorption dose up to 50 kGy. The tensile strength of irradiated PP/POSS nanocomposites decreased at high absorption dose due to the main chain scission of PP by radiation. The PP/POSS nanocomposites showed improved thermal stability due to the formation of crosslinked network between PP and POSS by radiation. %0 journal article %@ 1386-0291 %A Hiebl, B.,Mrowietz, C.,Braune, S.,Franke, R.-P.,Plendl, J.,Jung, F. %D 2009 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 173-179 %R doi:10.3233/CH-2009-1232 %T Intravital microscopy of the capillary perfusion in the corium limbi of the third toe of the minipig %U https://doi.org/10.3233/CH-2009-1232 1-2 %X Several methods are available today for the investigation of microcirculation in animal models, but they can be invasive and time-consuming depending on the area investigated. In particular, non-invasive methods that can be conducted rapidly and without dye or tracer injections are in demand.,The cutaneous microcirculation can be easily studied in the dorsal corium limbi of the third toe of the porcine forelimb using intravital microscopy – analogous to nail fold capillary microscopy in humans. The capillary microscopy system consists of a reflected-light microscope with a cold light source, green and infrared filters and a video camera. The video sequences were recorded using the image capture system Framegrabber (Imagenation PXC-200) and a PC (with an Intel Core 2 Duo processor, 1024 MB RAM, 160 GB hard disk, Windows XP Pro), and stored via a DVD recorder (Panasonic LQ-MD800).,Quantification of capillary erythrocyte flow velocities was performed using the computer-assisted image analysis system Cap Image Version 8.5 which includes a movie tool as a video sequence storage medium. The method allows estimation of capillary density and tortuosity as well as capillary circulation in the anesthetized pig within a few minutes. First measurements were made after anesthesia induction followed by further measurements during anesthesia maintenance (3 minutes each). No differences in capillary circulation were found.,The present method is thus very well suited for long-term microcirculation measurements in pigs, e.g., to evaluate therapeutic interventions in the ischemic limb model. %0 conference lecture %@ %A Mrowietz, C.,Hiebl, B.,Schunk, W.-H.,Blaschke, F.,Jung, F. %D 2009 %J Jahrestagung der DGKMH %N %P %T Einfluss von Eikosanoiden auf die spontane und die Kollagen-, Ristocetin- und ADP-induzierte Thrombozytenaggregation %U %X %0 journal article %@ 1386-0291 %A Franke, R.P.,Fuhrmann, R.,Hiebl, B.,Mrowietz, C.,Jung, F. %D 2009 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 149-155 %R doi:10.3233/CH-2009-1229 %T Permeability of technical and biological tissues %U https://doi.org/10.3233/CH-2009-1229 1-2 %X The permeability of a material is described by the amount of substances (gases, liquids, particles) passing through pores and/or interstices of the material in a certain time. In medicine and biotechnology the permeability is given usually as the amount of water (ml × cm−2 × min−1) permeating per area and time unit through the material. Vascular prostheses are described e.g. as high porous prostheses (e.g. Dacron™: 1500–4000 (ml × cm−2 × min−1)) or as low porous prostheses (e.g. ePTFE: 200–1000 (ml × cm−2 × min−1)).,The permeability of blood capillaries is characterized by the exchange of nutrients, metabolites and breathing gases. Capillary permeability and the transport of the permeates through tissues are the key processes for the supply of organs and tissues where especially the protein transport through tissues is described by diffusive and/or convective terms.,The vascular permeability is governed by the permeability of the intimal endothelial cells. The major influence is exerted by the interendothelial binding which can change drastically in a very short time. This is demonstrated by the fast development of interstitial lung oedema in case of septical shock. The permeability is an integral indicator of tissue and organ function.,It is possible to assess the permeability of native and engineered tissues precisely with a recently developed system. First results will be shown. %0 journal article %@ 1042-3931 %A Park, J.-W.,Leithaeuser, B.,Gerk, U.,Vrsansky, M.,Jung, F. %D 2009 %J The Journal of Invasive Cardiology %N 9 %P 446-450 %T Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO) for Stroke Prevention in Atrial Fibrillation: 2-Year Outcome %U 9 %X Purpose. In more than 90% of patients with atrial fibrillation (AF), stroke is due to thrombotic embolization from the left atrial appendage (LAA). Transcatheter occlusion with percutaneous left atrial appendage transcatheter occlusion (PLAATO), a self-expanding, membrane-covered spherical nitinol cage, is feasible and an alternative to anticoagulation therapy. Methods. This was a single-center prospective registry study for verification of stroke risk reduction in patients with AF 2 years after PLAATO. Results. Seventy-three patients with AF (permanent 65, paroxysmal 8) in whom anticoagulation therapy was contraindicated or rejected underwent transcatheter LAA occlusion with PLAATO. One patient died periprocedurally due to implant embolization, and 1 patient underwent open-heart surgery because of implant instability. The remaining 71 patients were followed for 24 months. In 52 patients a stable anchoring of the PLAATO device without migration or dislocation was documented by transesophageal echocardiography (TEE). No thrombotic deposition was found on the LA luminal surface of the device. Statistically, in our patient cohort, 7 strokes would have been expected without any treatment within 24 months. In fact, no strokes were reported. Ten out of 71 patients died during follow up: 6 in our hospital and 4 at home. None of them died from a stroke. Conclusions. Ninety-seven percent of AF patients were successfully treated with PLAATO. After mechanical LAA occlusion, the 2-year risk of stroke in AF patients is markedly reduced. Therefore, this therapeutic concept is a clear alternative for patients with AF and contraindications for oral anticoagulation. %0 journal article %@ 1386-0291 %A Baskurt, O.K.,Boynard, M.,Cokelet, G.C.,Connes, P.,Cooke, B.M.,Forconi, S.,Liao, F.,Hardeman, M.R.,Jung, F.,Meiselman, H.J.,Nash, G.,Nemeth, N.,Neu, B.,Sandhagen, B.,Shin, S.,Thurston, G.,Wautier, J.L. %D 2009 %J Clinical Hemorheology and Microcirculation %N 2 %P 75-97 %R doi:10.3233/CH-2009-1202 %T New guidelines for hemorheological laboratory techniques %U https://doi.org/10.3233/CH-2009-1202 2 %X No abstract %0 conference lecture %@ %A Franke, R.-P.,Fuhrmann, R.,Mrowietz, C.,Rickert, D.,Hiebl, B.,Jung, F. %D 2009 %J 15th Conference of the European Society of Clinical Hemorheology and Microcirculation %N %P %T Reduced diagnostic value of lactate dehydrogenase (LDH) in the presence of radiographic contrast media %U %X %0 journal article %@ 1386-0291 %A Leithaeuser, B.,Mrowietz, C.,Hiebl, B.,Pindur, G.,Jung, F. %D 2009 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 167-171 %R doi:10.3233/CH-2009-1231 %T Capillary bleeding under oral anticoagulation %U https://doi.org/10.3233/CH-2009-1231 1-2 %X Background: Oral anticoagulants are routinely used for prevention of thromboembolism in cardiac, arterial or venous diseases. Hemorrhages are serious treatment complications, frequently occurring under long-term and/or high-dose regiments. From animal experiments it is known that coumarin-type anticoagulants may cause capillary dilatation and increased permeability, red blood cell extravasation and punctate bleeding. Controlled human trials are lacking.,Methods: 31 patients under oral anticoagulation were examined by video capillary microscopy. 52 patients with comparable diseases and treatment but without oral anticoagulation served as controls. Nailfold capillaries of four fingers of each hand were examined and analyzed off-line according to the following criteria: (1) numbers of capillaries investigated, (2) numbers of capillary bleedings, and (3) bleeding incidence (bleedings per 100 capillaries).,Results: In 23 out of 31 patients (74.2%) capillary bleedings were observed. The bleeding incidence ranged from 0.33 to 4.29 per 100 capillaries. In contrast, only 4 out of 52 controls were detected with capillary bleedings (2.1%, p<0.001). The bleeding incidence was 0.34–2.41. In patients on anticoagulation there was no correlation between the number of capillary bleedings and the INR or Quick values. During a two year follow-up of patients on oral anticoagulation no significant difference was found in terms of clinically obvious bleedings in patients with or without capillary bleedings.,Conclusion: This study shows that capillary bleedings can be demonstrated in patients on oral anticoagulation. Bleedings occur independent of the INR-value. Thus, other factors than the vitamin-k-dependent coagulation effect seem to be causal for the damage of microvessels. Further, the evidence of capillary bleedings is not a prognostic indicator for future hemorrhage. %0 journal article %@ 0044-2771 %A Clevert, D.-A.,Jung, E.-M.,Stock, K.F.,Weckbach, S.,Feuerbach, S.,Reiser, M.,Jung, F. %D 2009 %J Zeitschrift fuer Gastroenterologie %N 12 %P 1195-1202 %R doi:10.1055/s-0028-1109396 %T Evaluation of Malignant Liver Tumors: Biphasic MS-CT versus Quantitative Contrast Harmonic Imaging Ultrasound - Biphasisches Multislice-CT im Vergleich zum quantitativen Contrast-Harmonic-Imaging bei der Beurteilung von malignen Lebertumoren %U https://doi.org/10.1055/s-0028-1109396 12 %X Purpose: It was the aim of our study to establish the extent to which contrast enhancement with SonoVue® in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of malignant hepatic tumors. Materials and Methods: One hundred patients with histologically confirmed malignant or benign hepatic tumors (maximum size 5 cm) were analyzed. We used a high-end ultrasound machine (Logic 9, GE Healthcare, Milwaukee, WI, USA), with a multifrequency curved array transducer (2.5 - 4 MHz), Contrast-enhanced ultrasound (bolus injection 2.4 mL SonoVue®) was carried out with the intermittent breath-holding technique. Native vascularization was analyzed with power Doppler sonography. The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in the true detection mode during the arterial, portal venous and late phases. The mechanical index was set at 0.15. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). Biphasic 16- or 64-slice multislice computed tomography served as reference method in nearly all cases. Results: One hundred patients with 59 malignant (43 colon, 5 breast, 2 endocrine metastases, 7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (12 circumscribed fatty changes, 2 abscesses, 7 focal nodular hyperplasias, 5 complicated cysts and 15 hemangiomas) tumors were included. The CT classification was true positive in 71 of 92 patients, false negative in 8 cases, and in 13 cases no final diagnosis was possible; sensitivity was 96.7 % and specificity was 71.4 % for CT. The quantitative contrast harmonic imaging ultrasound classification was true positive in 98 of 100 patients and false negative in 2 cases; the sensitivity was 98.6 % and the specificity was 96.6 %. The Fisher test showed a significant difference at p < 0.05. No investigator-dependency was noted. Conclusion: In our study contrast-enhanced ultrasound was more accurate than multislice computed tomography in the prediction of malignancy and benignity of liver tumors. -,Ziel: Wir untersuchten die klinische Bedeutung der kontrastverstärkten Sonografie mit SonoVue® in Kombination mit der Quantifizierung der Kontrastmitteldynamik zur Detektion maligner Lebertumoren. Material und Methoden: In die Studie wurden 100 Patienten mit histologisch gesicherten, malignen oder benignen Lebertumoren (maximale Größe bis 5 cm) eingeschlossen. Wir verwendeten hierfür ein High-End-Ultraschallgerät (Logic 9, GE Healthcare, Milwaukee, WI, USA) mit einem Multihertz-Konvexschallkopf (2,5 - 4 MHz). Die kontrastverstärkte Sonografie (Bolusinjektion von 2,4 mL SonoVue®) wurde in der Technik des intermittierenden Atemanhaltens durchgeführt. Die Vaskularisation der Tumoren wurde zunächst mittels Power-Doppler beurteilt. Im Anschluss daran erfolgte dann die Kontrastmitteluntersuchung im „True Detection Mode”, dem integrierten Kontrastmittelprogramm des High-End-Ultraschallgeräts. Die dynamische Kontrastmitteluntersuchung des Patienten wurde dabei in der arteriellen Phase, der portalen Phase und der Spätphase durchgeführt. Der mechanische Index lag dabei bei 0,15. Die Analyse der Lebertumorperfusion erfolgte durch Nachverarbeitung der Rohdaten (time intensity curve [TIC] analysis). Als Referenzmethode diente eine biphasische 16- oder 64-Zeilen-CT-Untersuchung. Ergebnisse: 100 Patienten mit 59 malignen (43 Kolonkarzinom-Metastasen, 5 Mammakarzinom-Metastasen, 2 Metastasen von endokrinen Tumoren, 7 hepatozelluläre Karzinome und 2 Metastasen von Nierentumoren) und 41 benignen Lebertumoren (12 umschriebene Fettververteilungsstörungen, 2 Abszesse, 7 fokal noduläre Hyperplasien, 5 „komplizierte Zysten” und 15 Hämangiome) wurden in die Studie eingeschlossen. Die CT-Artdiagnose „benigne - maligne” war richtig positiv bei 71 von 92 Patienten, falsch negativ bei 8 Patienten und in 13 Fällen war es nicht möglich, eine endgültige Diagnose zu stellen. Die Sensitivität der Computertomografie lag bei 96,7 %, die Spezifität betrug 71,4 %. Quantitativer, kontrastverstärkter Ultraschall lag mit seiner Klassifikation der Leberherde in benigne und maligne Läsionen bei 98 von 100 Patienten richtig, 2 Patienten wurden falsch negativ klassifiziert. Die Sensitivität der Methode lag damit bei 98,6 % die Spezifizität bei 96,6 %. Im Fischer-Test ergaben sich signifikante Unterschiede zwischen den beiden diagnostischen Modalitäten bei p < 0,05. Es wurde keine Untersucherabhängigkeit festgestellt. Schlussfolgerung: In unserer Studie war der kontrastverstärkte Ultraschall zur Vorhersage von Benignität oder Malignität bei Leberherden genauer als die Multislice-Computertomografie. %0 conference lecture %@ %A Hiebl, B.,Jung, F.,Schossig, M.,Scharnagl, N.,Richau, K.,Niehues, S. %D 2009 %J 15th Conference of the European Society of Clinical Hemorheology and Microcirculation %N %P %T In vitro evaluation of a nitinol based vein cuff for external valvuloplasty %U %X %0 journal article %@ 1386-0291 %A Franke, R.P.,Fuhrmann, R.,Hiebl, B.,Jung, F. %D 2009 %J Clinical Hemorheology and Microcirculation %N 1-2 %P 181-187 %R doi:10.3233/CH-2009-1233 %T Influence of radiographic contrast media on the secretion of vasoactive substances by primary human umbilical venous endothelial cells (HUVEC): Prospective, controlled, in vitro comparative study %U https://doi.org/10.3233/CH-2009-1233 1-2 %X Besides the desirable effect of roentgen ray absorption radiographic contrast media (RCM) can also have varying adverse effects. Under discussion, as a possible cause, are microcirculatory disorders resulting from morphological alterations in erythrocytes and endothelial cells.,Therefore, the contrast media-induced release of vasoactive substances (prostacyclin, endothelin-1, and nitric oxide (NO)) from human endothelial cells (HUVEC) induced by two commercially available RCMs (Iodixanol 320, Iomeprol 350) was tested in a controlled in-vitro study.,The results show that RCMs lead to endothelial cell trauma in vitro, which is apparent in the release of prostacyclin and endothelin-1, while NO release was not affected. The endothelin-1 release after incubation with Iodixanol was similar to the release in the control cultures. In comparison, lower endothelin-1 levels were measured in the cultures incubated with Iomeprol at all 3 time points indicating a more significant cell trauma. Prostacyclin release – also an indicator of traumatization of endothelial cells – increased after addition of both contrast agents. The highest release was found after incubation with Iomeprol 350. %0 conference poster %@ %A Hiebl, B.,Kratz, K.,Fuhrmann, R.,Jung, F.,Lendlein, A.,Franke, R.-P. %D 2009 %J MRS Spring Meeting 2009 %N %P %T In vivo degradation behavior of PDC multiblock copolymers containing poly(para-dioxanone) hard segments and crystallizable poly(epsilon-caprolactone) switching segments %U %X %0 conference paper %@ %A Hiebl, B.,Kratz, K.,Fuhrmann, R.,Jung, F.,Lendlein, A.,Franke, R.-P. %D 2009 %J Active Polymers - MRS Symposium Proceedings, MRS Spring Meeting 2009 %N %P NN06-05 %R doi:10.1557/PROC-1190-NN06-05 %T In vivo degradation behavior of PDC multiblock copolymers containing poly(para-dioxanone) hard segments and crystallizable poly(epsilon-caprolactone) switching segments %U https://doi.org/10.1557/PROC-1190-NN06-05 %X %0 conference lecture %@ %A Hiebl, B.,Fuhrmann, R.,Jung, F.,Kratz, K.,Lendlein, A.,Franke, R.-P. %D 2009 %J 15th Conference of the European Society of Clinical Hemorheology and Microcirculation %N %P %T Degradation of and angiogenesis around multiblock copolymers containing poly(Rho-dioxanone)- and poly(Epsilon-caprolactone)-segments subcutaneously implanted in the rat neck %U %X %0 conference lecture %@ %A Jung, F. %D 2009 %J Seminar der Hochschule Senftenberg %N %P %T Interaktion von Thrombozyten mit koerperfremden Oberflaechen - Haemokompatibilitaet %U %X %0 journal article %@ 0920-5268 %A Hiebl, B.,Mueller, C.,Jung, F.,Huenigen, H.,Hamm, B.,Plendl, J.,Niehues, S.M. %D 2009 %J Applied Cardiopulmonary Pathophysiology %N 4 %P 318-321 %T Macro- and micromorphometric studies of the vascular structures from the Göttingen® minipig %U 4 %X Porcine models have become increasingly popular in cardiovascular research, because physiological and anatomical features of the cardiovascular system from pigs including the coronary vascular system and the coronary collateral vessels are comparable to humans. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. In contrast Göttingen® minipigs have a characteristic growth curve that avoids the dramatic increase in weight in adulthood seen in farm pigs. The Göttingen® minipig is especially suitable for long-term studies because of its inherent small size and ease of handling, even at full maturity, which is reached at 2 y of age compared with 3 y for domestic pigs. However, there is still a need on detailed information about the macro- and microvascular characteristics of the vascular system from the Göttingen® minipigs.,The study was aimed to describe the macro- and microvascular characteristics of adult Göttingen® minipigs (n=18) by use of CT-imaging and histology over a time period of 4 months starting from 16 months of age up to 20 months. The animals showed no clinical symptoms of disease and were kept in-house at a light/dark rhythm of 12:12 under defined climatic conditions. The experiments were licensed by the regional authorities for health and social affairs (LaGeSo), Berlin. The study included the measurement of the length and of the luminal diameter of arteries and veins from the neck, thorax, abdomen, and limbs which are frequently used in experiments with pigs. In addition microscopical and histological parameters (luminal vessel diameter, thickness of the tunica externa, tunica media, and tunica interna) were studied on hematoxylin-eosin-stained sections of the blood vessel. %0 journal article %@ 1042-3931 %A Oezbek, C.,Bay, W.,Jochum, L.,Jung, F.,Bach, R. %D 2008 %J The Journal of Invasive Cardiology %N 1 %P 9-13 %T Clinical and angiographic results after implantation of a passive-coated coronary stent in patients with acute myocardial infarction %U 1 %X Background. Key insights into the role of platelets in acute myocardial infarction (AMI) and unstable angina have led to the development of the polymer-coated stent, Camouflage®. Coating of stents is an elegant method to minimize interactions between platelets and the stent surface and the vascular response following stent implantation. Methods. This single-center prospective registry was performed to estimate the in-hospital, 30-day and 180-day event rate (death, revascularization, reinfarction and pathological stress test at 180 days) in an everyday patient population with AMI with immediate percutaneous coronary intervention. There were 44 males (65.7%) and 23 females (34.3%); 53 patients (79.1%) had hypertension, 11 (16.4%) were diabetic, and 32 (47.8%) had elevated LDL cholesterol. The mean age was 60.7 ± 11.6 years. Results. Sixtyseven patients with AMI (STEMI: 56.7%, NSTEMI: 43.3%) were included. Clinical data at the 30-day and 180-day follow up were avai. %0 conference lecture (invited) %@ %A Jung, F. %D 2008 %J Current Perspectives of the Extracorporeal Circulation %N %P %T Interaction of blood with body foreign surfaces - Haemocompatibility %U %X %0 journal article %@ 1386-0291 %A Jung, F.,Mrowietz, C.,Rickert, D.,Hiebl, B.,Park, J.-W.,Franke, R.-P. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1 %P 1-11 %T The effect of radiographic contrast media on the morphology of human erythrocytes %U 1 %X Echinocyte formation is associated with a rigidification of the cells that possibly affects capillary diffusion and, consequently, the tissue's oxygen supply. This study examines how many echinocytes appeared after the addition of various concentrations of radiographic contrast media (RCM) (Iodixanol 320, Iohexol 350, Iopromide 370, Iomeprol 350 and Iomeprol 400 mg Iodine/ml) compared to red blood cells in isotonic saline solution as well as in autologous plasma.,Isotonic saline solution, Iodixanol, Iohexol, Iomeprol 350, Iomeprol 400 and Iopromide in concentrations of 10%, 20% or 40% were added to the plasma of six healthy subjects. Subsequently, the erythrocytes were resuspended in these RCM/plasma mixtures, incubated for 5 minutes at 37°C and then examined under the microscope.,The various mixtures and concentrations of the RCM in the mixture all had a significant effect on the number of discocytes (p<0.0001). The percentage of discocytes for all concentrations significantly depended on the RCM/plasma mixture (p=0.0097).,Of all the RCM/plasma mixtures used as well as of the NaCl/plasma mixtures, the Iodixanol/plasma mixture showed the most similar discocyte fraction compared to red blood cells in the autologous plasma. At the same time, while Iodixanol in this respect differed from all other RCMs, the other RCMs only differed little from one another with respect to the discocyte fraction. %0 journal article %@ 1082-720X %A Park, J.-W.,Leithaeuser, B.,Hill, P.,Jung, F. %D 2008 %J Annals of Noninvasive Electrocardiology %N 2 %P 171-179 %R doi:10.1111/j.1542-474X.2008.00217.x %T Resting Magnetocardiography Predicts 3-Year Mortality in Patients Presenting with Acute Chest Pain without ST Segment Elevation %U https://doi.org/10.1111/j.1542-474X.2008.00217.x 2 %X Magnetocardiography (MCG) as a noninvasive, noncontact and risk-free diagnostic method predicts ischemic coronary artery disease (CAD) in patients with acute chest pain at admission with high accuracy. However, it remains unclear whether MCG findings can add prognostic information.,A cohort of 402 consecutive patients presenting at the intensive care unit (ICU) with acute chest pain without ST segment elevation (NSTEMI) were included in a prospective registry. In order to prove the prognostic value of MCG a head-to-head comparison of the admission MCG, ECG, TnI, and ECHO tests was made. %0 journal article %@ 1386-0291 %A Park, J.-W.,Leithaeuser, B.,Vrsansky, M.,Jung, F. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 21-32 %R doi:10.3233/CH-2008-1064 %T Dobutamine stress magnetocardiography for the detection of significant coronary artery stenoses – A prospective study in comparison with simultaneous 12-lead electrocardiography %U https://doi.org/10.3233/CH-2008-1064 1-4 %X Background: Exercise electrocardiography is an imperfect test for the detection of coronary artery disease (CAD). Magnetocardiography detects cardiac electrical disturbances associated with myocardial ischemia. We prospectively investigated the accuracy of high-dose dobutamine stress magnetocardiography (DS-MCG) and simultaneous electrocardiography (DS-ECG) for the detection of significant CAD.,Methods: 100 patients with an intermediate pre-test probability for CAD underwent DS-MCG using a multichannel magnetometer prior to invasive coronary angiography. Patients were examined at rest and during a standard dobutamine–atropine scheme. Significant reduction of epicardial current strength/density during stress, reconstructed from the magnetic field map and superposed on a virtual heart model indicates myocardial ischemia. A 12-lead DS-ECG was recorded simultaneously. Significant coronary artery stenosis was defined as ≥70% of lumen reduction.,Results: Without β-blocker all 100 patients reached the targeted heart rate. The image quality of DS-MCG and DS-ECG was sufficient for analysis in all patients. In 19 patients CAD was ruled out angiographically. Thirty two or seven patients revealed coronary artery stenoses of 30–49% or of 50–69%, respectively. In 42 patients we found significant stenoses of ≥70%. In 41 of these patients DS-MCG revealed myocardial ischemia. The sensitivity of DS-MCG and DS-ECG for the detection of significant coronary artery stenosis was 97.6% and 26.2%, the specificity of DS-MCG and DS-ECG 82.8% and 82.8%, respectively. %0 journal article %@ 1386-0291 %A Leithaeuser, B.,Zielske, D.,Seyfert, U.T.,Jung, F. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 293-302 %R doi:10.3233/CH-2008-1092 %T Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel %U https://doi.org/10.3233/CH-2008-1092 1-4 %X Purpose: The use of clopidogrel is standard in interventional cardiology. Haemorrhage occurs in some patients, which implies a need for a non-transfusional therapy. Desmopressin showed its efficacy as an antidote of acetylsalicylic acid. In this trial the effects of desmopressin on platelet glycoproteins and the platelet's ability to aggregate under the influence of clopidogrel are studied.,Methods: The trial was conducted as an open, prospective, single-centre, randomised pilot study with n=17 healthy volunteers in a parallel-group design. 1 h after an oral loading dose of 375 mg clopidogrel the effects of a single-dose of 300 μg of Octostim® nasal spray (n=9) on platelet aggregation, activity of platelets on the density of membrane-bound receptors are measured.,Results: Ristocetin cofactor and platelet reactivity rose significantly after the administration of Octostim® nasal spray with 31.9% and 5.3%, respectively (p=0.0329; p=0.0414). The ADP-induced platelet aggregation increased after the administration of Octostim® nasal spray by approximately 20% (p=0.0564). The fraction of CD62- and CD63-positive platelets did not change after clopidogrel nor after desmopressin (p=0.4203; p=0.6774). The density of GPIIb/IIIa receptors per platelet did not change after desmopressin (p=0.9652). The density of GPIb/IX receptors per platelet rose after desmopressin without reaching the level of significance (p=0.0802). In the desmopressin group alone the receptor density rose by 5.5% (p=0.0783).,Conclusion: The administration of desmopressin improved the primary haemostasis when given in addition to a clopidogrel therapy. Patients undergoing a heart catheter procedure with clopidogrel might benefit from the use of desmopressin when having a bleeding episode. %0 journal article %@ 1386-0291 %A Mrowietz, C.,Hiebl, B.,Franke, R.P.,Park, J.-W.,Jung, F. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 281-286 %R doi:10.3233/CH-2008-1097 %T Reversibility of echinocyte formation after contact of erythrocytes with various radiographic contrast media %U https://doi.org/10.3233/CH-2008-1097 1-4 %X Various radiographic contrast media (RCM) significantly influence the morphology of erythrocytes, especially the formation of echinocytes [Scand. J. Clin. Lab. Invest. 35 (1975), 1–43; Microvasc. Res. 60 (2000), 193–200; Herz 23 (2003), 35–41]. Microscopic studies, however, have shown that these changes of erythrocyte morphology are possibly reversible [Acta Radiol. 37 (1996), 214–217].,The aim of this study was to proof if the RCM-induced echinocyte formation can be reversed by a resuspension in autologous plasma. In this study four RCMs were tested (Iodixanol, Iohexol, Iomeprol and Iopromide).,These RCM induced echinocyte formation (after suspension of erythrocytes in plasma/RCM mixtures for 10 min at 37°C), which was reversible after resuspension in autologous RCM-free plasma (resuspension time 5 min at 37°C). Especially for Iomeprol and Iopromide – the RCMs which induced the strongest echinocyte formation – an echinocyte reduction from 94.2% to 44.5% and for Iopromide from 80.6% to 50.4% occurred. The echinocyte formation was influenced by the type of RCM as well as by the RCM concentration. The same was true for the reversibility of echinocyte formation due to resuspension in autologous plasma (type of RCM: p≤0.0001; concentration of RCM: p=0.0847). Iodixanol was associated with the least numbers echinocytes formed (after suspension in the plasma/RCM-mixture as well as after the resuspension in autologous plasma). A 100% reversibility back to discocytes was observed in none of the RCMs after resuspension in autologous RCM-free plasma. %0 journal article %@ 1386-0291 %A Park, J.-W.,Leithaeuser, B.,Sommer, F.,Jung, F. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 323-328 %R doi:10.3233/CH-2008-1096 %T Sublingual application of liquid nitrendipine does not result in critical hypotension in healthy volunteers under phosphodiesterase-5 inhibition %U https://doi.org/10.3233/CH-2008-1096 1-4 %X Introduction: The introduction of phosphodiesterase-5 inhibitors as sildenafil, tadalafil, or vardenafil, has tremendously improved the treatment of erectile dysfunction. Patients with the common comorbidity of cardiovascular disease and erectile dysfunction, however, are at risk for critical hypotension in case of self-treatment of cardiac angina with nitrates after the intake of a phosphodiesterase-5 inhibitor.,Methods: We evaluated the safety of 5 mg sublingual nitrendipine after pre-treatment of 8 healthy male volunteers (42.1±9.6 yrs) with 20 mg tadalafil. Randomly four different protocols were compared using six hours blood pressure recordings: (1) baseline, (2) 20 mg tadalafil, (3) 5 mg nitrendipine, and (4) 20 mg tadalafil+5 mg nitrendipine.,Results: The blood pressure was not significantly affected by tadalafil. Nitrendipine lowered the systolic blood pressure significantly by −1.91 mmHg (p=0.0079). The co-medication of 20 mg tadalafil+5 mg nitrendipine lowered the blood pressure significantly by −2.86 mmHg (p<0.0001). There was no statistically significant difference between tadalafil and nitrendipine (p=0.598). Relevant hypotension (systolic blood pressure of <85 mmHg) was observed in none of the study individuals during the four protocols.,Conclusions: Sublingual nitrendipine seems to be safe for self-treatment of an anginal attack in patients with stable coronary artery disease, who have taken a phosphodiesterase-5 inhibitor. However, our findings on hemodynamic changes in apparently healthy volunteers have to be confirmed in patients with coronary artery disease. %0 journal article %@ 1386-0291 %A Matschke, K.,Jung, F. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 265-279 %R doi:10.3233/CH-2008-1093 %T Regulation of the myocardial microcirculation %U https://doi.org/10.3233/CH-2008-1093 1-4 %X No abstract %0 journal article %@ 1726-4170 %A Vetter, M.,Churkina, G.,Jung, M.,Reichstein, M.,Zaehle, S.,Bondeau, A.,Chen, Y.,Ciais, P.,Feser, F.,Freibauer, A.,Geyer, R.,Jones, C.,Papale, D.,Tenhunen, J.,Tomelleri, E.,Trusilova, K.,Viovy, N.,Heimann, M. %D 2008 %J Biogeosciences %N 2 %P 561-583 %R doi:10.5194/bg-5-561-2008 %T Analyzing the causes and spatial pattern of the European 2003 carbon flux anomaly using seven models %U https://doi.org/10.5194/bg-5-561-2008 2 %X Globally, the year 2003 is associated with one of the largest atmospheric CO2 rises on record. In the same year, Europe experienced an anomalously strong flux of CO2 from the land to the atmosphere associated with an exceptionally dry and hot summer in Western and Central Europe. In this study we analyze the magnitude of this carbon flux anomaly and key driving ecosystem processes using simulations of seven terrestrial ecosystem models of different complexity and types (process-oriented and diagnostic). We address the following questions: (1) how large were deviations in the net European carbon flux in 2003 relative to a short-term baseline (1998–2002) and to longer-term variations in annual fluxes (1980 to 2005), (2) which European regions exhibited the largest changes in carbon fluxes during the growing season 2003, and (3) which ecosystem processes controlled the carbon balance anomaly .,In most models the prominence of 2003 anomaly in carbon fluxes declined with lengthening of the reference period from one year to 16 years. The 2003 anomaly for annual net carbon fluxes ranged between 0.35 and –0.63 Pg C for a reference period of one year and between 0.17 and –0.37 Pg C for a reference period of 16 years for the whole Europe.,In Western and Central Europe, the anomaly in simulated net ecosystem productivity (NEP) over the growing season in 2003 was outside the 1σ variance bound of the carbon flux anomalies for 1980–2005 in all models. The estimated anomaly in net carbon flux ranged between –42 and –158 Tg C for Western Europe and between 24 and –129 Tg C for Central Europe depending on the model used. All models responded to a dipole pattern of the climate anomaly in 2003. In Western and Central Europe NEP was reduced due to heat and drought. In contrast, lower than normal temperatures and higher air humidity decreased NEP over Northeastern Europe. While models agree on the sign of changes in simulated NEP and gross primary productivity in 2003 over Western and Central Europe, models diverge in the estimates of anomalies in ecosystem respiration. Except for two process models which simulate respiration increase, most models simulated a decrease in ecosystem respiration in 2003. The diagnostic models showed a weaker decrease in ecosystem respiration than the process-oriented models. Based on the multi-model simulations we estimated the total carbon flux anomaly over the 2003 growing season in Europe to range between –0.02 and –0.27 Pg C relative to the net carbon flux in 1998–2002. %0 journal article %@ 1386-0291 %A Leithaeuser, B.,Gerk, U.,Mrowietz, C.,Jung, F.,Park, J.-W. %D 2008 %J Clinical Hemorheology and Microcirculation %N 1-4 %P 287-292 %R doi:10.3233/CH-2008-1091 %T Influence of xantinole nicotinic acid on cutaneous microcirculation in patients with coronary artery disease and hyperlipoproteinemia %U https://doi.org/10.3233/CH-2008-1091 1-4 %X Xantinole nicotinic acid (NA) dose dependently lowers plasma levels of atherogenic lipoproteins and increases blood flow through vasodilation. The aim of this study was to evaluate the effect of NA on cutaneous microcirculation in patients with coronary artery disease and hyperlipidemia. In this open pilot study, five men and three women (74.2±9.1 yrs; 81.4±7.9 kg; 171.6±7.0 cm) with angiographically proven coronary artery disease and hyperlipidemia were included. Nailfold capillary microscopy was used for measurements of erythrocyte velocities at rest and after three minutes of ischemia, before and one hour after intake of 1000 mg of NA.,The blood pressure (120±12/73±8 mmHg vs. 113±10/72±5 mmHg; p=0.19/0.83) and the heart rate (72±8/min vs. 70±7/min; p=0.38) remained unchanged. The mean capillary red blood cell velocity at rest (vRBC; 0.27±0.23 mm/s vs. 0.32±0.18 mm/s; p=0.089) and the time to maximal post ischemia erythrocyte velocity (tpeak; 21.0±7.9 s vs. 24.3±15.5 s; p=0.49) did not change. The maximal post ischemic erythrocyte velocity (vmaxRBC; 0.93±0.33 mm/s vs. 1.19±0.19 mm/s; p=0.0096) raised slightly but significantly, the duration of post-ischemia hyperemia (DpH; 101±16 s vs. 127±15 s; p=0.0005) increased markedly. One patient reported about flush in the whole body.,The administration of 1000 mg of NA resulted in a significant improvement of the cutaneous microcirculation in patients with coronary artery disease and hyperlipidemia.,Keywords %0 conference lecture %@ %A Franke, R.-P.,Fuhrmann, R.,Hiebl, B.,Jung, F. %D 2008 %J Clinical Hemorheology and Microcirculation, 13th International Congress of Biorheology and 6th International Conference on Clinical Hemorheology %N %P %T Influence of various radiographic contrast media on the buckling of endothelial cells %U %X %0 conference lecture %@ %A Jung, F.,Hiebl, B.,Mrowietz, C.,Ploetze, K.,Matschke, K. %D 2008 %J 27. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Critical hematocrit and oxygen partial pressure in the beating heart of pigs %U %X %0 book part %@ %A Leithaeuser, B.,Gerk, U.,Mrowietz, C.,Jung, F.,Park, J.W. %D 2008 %J Aktuelles aus der Klinischen Haemorheologie und Mikrozirkulation %N %P 101-108 %T Einfluss von Xantinolnikotinat auf die kutane Mikrozirkulation bei Patienten mit koronarer Herzerkrankung und Hyperlipoproteinaemie %U %X %0 conference lecture %@ %A Jung, F.,Mrowietz, C.,Franke, R.-P. %D 2008 %J 27. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Extreme segmentale Einengungen kutaner Kapillaren beim Menschen %U %X %0 conference lecture %@ %A Hiebl, B.,Rickert, D.,Fuhrmann, R.,Jung, F.,Lendlein, A.,Franke, R.-P. %D 2008 %J MRS Fall Meeting 2008, Symposium HH, Advances in Material Design for Regenerative Medicine, Drug Delivery, and Targeting/Imaging %N %P %T Tissue Integration of Two Different Shape-Memory Polymers with Poly(e-Caprolactone) Switching Segment in Rats %U %X %0 conference lecture (invited) %@ %A Lendlein, A.,Franke, R.-P.,Jung, F.,Behl, M. %D 2008 %J Lenkungsausschusssitzung HGF %N %P %T Program Regenerative Medicine %U %X %0 conference lecture %@ %A Choi, J.-H.,Jung, C.-H.,Kim, D.-K.,Suh, D.-H.,Nho, Y.-C.,Kang, P.-H.,Ganesan, R. %D 2008 %J 15th International Meeting on Radiation Processing %N %P %T Preparation of polymer/POSS nanocomposites by radiation processing %U %X %0 book part %@ %A Jung, F.,Matschke, K. %D 2008 %J Aktuelles aus der Klinischen Haemorheologie und Mikrozirkulation %N %P 78-87 %T Regulation der myokardialen Mikrozirkulation %U %X %0 book part %@ %A Franke, R.-P.,Fuhrmann, R.,Mrowietz, C.,Jung, F. %D 2008 %J Aktuelles aus der Klinischen Haemorheologie und Mikrozirkulation %N %P 28-41 %T Einfluss von Roentgenkontrastmitteln auf die Morphologie humaner venoeser Endothelzellen %U %X %0 conference poster %@ %A Wickersheim, A.,Franke, R.-P.,Jung, F.,Lee, S.,Hiebl, B. %D 2008 %J 27. Jahrestagung der Deutschen Gesellschaft fuer Klinische Mikrozirkulation und Haemorheologie %N %P %T Enrichment of angiogenic stimulated CD14+ monocytes/macrophages (type II) to promote endothelialization on different extracellular matrices %U %X %0 conference lecture %@ %A Jung, F.,Hiebl, B.,Mrowietz, C.,Ploetze, K.,Matschke, K. %D 2008 %J 13. Congress of Biorheology, 6. International Conference on Clinical Hemorheology %N %P %T Critical hematocrit and oxygen partial pressure in the beating heart of pigs %U %X %0 journal article %@ 0920-5268 %A Jung, F.,Park, J.-W.,Franke, R.-P. %D 2007 %J Applied Cardiopulmonary Pathophysiology %N 1 %P 21-23 %T The inflated balloon – A possible cause of microvascular obstructions %U 1 %X A serious complication of coronary interventions is thromboembolism which might be caused by the detachment of platelet aggregates. One possible cause are small thrombogenic particles from the inflated balloon surface. The gliding layer of a balloon catheter was analyzed by means of a back scatter electron detector in a scanning electron microscope. The average element composition of the gliding layer was assessed of a non-inflated and a inflated balloon.,It could be shown that there was a continuous layer of silicon at the surface of the non-inflated balloon. After inflation of a new balloon, however, there was only a very thin and discontinuous silicon layer showing big holes. It seems to be possible that parts of the gliding layer flaked off the balloon surface leaving only “plaques of silicon”,on the balloon surface.,Detached silicon plaques surely would be thrombogenic and have therefore the potential to obstruct small myocardial,arterioles and capillaries. %0 journal article %@ 0340-644X %A Oezbek, C.,Ahmadsey, D.,Schilling, U.,Jung, F.,Latza, R.,Bach, R. %D 2007 %J Saarlaendisches Aerzteblatt %N 12 %P 9-12 %T Stoffwechseleinstellung bei Patienten mit koronarer Herzerkrankung und begleitenden Diabetes mellitus im Saarland %U 12 %X Im Jahr 2000 waren 10,9% der saarländischen Bevölkerung, entsprechend 116.489 Einwohnern, an Diabetes mellitus erkrankt. Damit ist die Diabetes-Prävalenz im Saarland im deutschen Vergleich,am höchsten [9]. Wird die von der WHO prognostizierte Zunahme des Diabetes um 44% bis zum Jahre 2030 als richtig unterstellt, wird sich diese Zahl auf 167.744 erhöhen. Die Anzahl könnte jedoch in den kommenden Jahren auch sinken, denn nach den Daten des statistischen Bundesamtes weisen mit 66,3 beziehungsweise 65,9 Gestorbenen je 100 000 Personen Thüringen und das Saarland bundesweit die höchste Sterblichkeit,an Diabetes mellitus auf. Brandenburg,und Bayern verzeichnen mit 18,3 beziehungsweise mit 18,9 Verstorbenen je 100 000 Personen die geringste Sterblichkeitsrate [13].,Führende Todesursache bei Patienten mit Diabetes mellitus sind kardiovaskuläre Erkrankungen [1]. Trotz therapeutischer Fortschritte haben Diabetiker weiterhin deutlich höhere Ereignisraten für kardiovaskuläre Morbidität und Mortalität als Nichtdiabetiker [12]. So haben Typ 2-Diabetiker ein etwa 3-mal so großes Risiko einen Herzinfarkt zu erleiden wie Gesunde,Nicht-Diabitker [7]. Die Prognose kardiovaskulärer Ereignisse wird durch die Qualität der Diabeteseinstellung entscheidend,beeinflußt (DECODE-Studie [15]). Am höchsten gefährdet sind die Patienten, die bereits eine strukturelle Herzerkrankung,(Koronare Herzerkrankung, Myokard- Hypertrophie, Klappenveränderungen) aufweisen. %0 journal article %@ 1007-9327 %A Jung, E.M.,Clevert, D.A.,Schreyer, A.G.,Schmitt, S.,Rennert, J.,Kubale, R.,Feuerbach, S.,Jung, F. %D 2007 %J World Journal of Gastroenterology : WJG %N 47 %P 6356-6364 %R doi:10.3748/wjg.v13.i47.6356 %T Evaluation of quantitative contrast harmonic imaging to assess malignancy of liver tumors: A prospective controlled two-center study %U https://doi.org/10.3748/wjg.v13.i47.6356 47 %X To establish the extent to which contrast enhancement with SonoVue in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of hepatic tumors. %0 journal article %@ 1386-0291 %A Franke, R.P.,Fuhrmann, R.,Park, J.-W.,Rickert, D.,Hiebl, B.,Jung, F. %D 2007 %J Clinical Hemorheology and Microcirculation %N 4 %P 329-338 %T The effect of radiographic contrast media on the morphology of human venous endothelial cells %U 4 %X Radiographic contrast media (RCM) can affect the morphology of red blood cells in very different ways but research on how they affect endothelial cell morphology is rudimentary. The effect of two conventional RCMs on human umbilical venous cells over the short term was studied in vitro under static conditions. Cell circumference length, the number of dissolved cell contacts and the number of denuded subendothelial matrix areas were interactively quantified by a computer imaging system after histochemical processing. 1.5 minutes after RCM exposure a significant effect of both RCMs on cell circumference length (CCL) compared to the control cells was evident (p=0.0001 each). The increase after iodixanol was larger than after iomeprol (p=0.0087). After five minutes of exposure, the CCL of exposed cells were significantly larger than those of control cells (p<0.0001 each). The CCL after exposure hardly differed anymore at that time (iomeprol/iodixanol: p=0.0547), though cells exposed to iomeprol tended to be bigger. After both iomeprol (p<0.0001) and iodixanol (p=0.0018), the number of dissolved cell contacts (DCC) increased compared to the control cells. The increases after either RCM were similar (p=0.9633). After five minutes of RCM exposure, the number of DCC was significantly higher than for the control cells (control/iomeprol: p<0.0001; control/iodixanol: p=0.0012). After exposure to iodixanol, significantly fewer DCC were recorded than after iomeprol (p=0.0018). At 1.5 minutes after RCM exposure, the number of denuded subendothelial matrix areas (DSMA) in the cell layer increased both after iomeprol (p<0.0002) and after iodixanol (p=0.0002) compared to the control cells. The increases with the two RCMs were similar (p=0.8618). After five minutes of exposure, the number of DSMA in the cell layer was significantly higher than for the control cells (control/iomeprol: p<0.0001; control/iodixanol: p=0.0015). However, after iodixanol significantly fewer DSMA were recorded than after iomeprol (iomeprol/iodixanol: p=0.0353). The number of dissolved cell/cell contacts and the number of denuded subendothelial matrix areas in the confluent endothelial layer were significantly greater after exposing the endothelial cells for five minutes to iomeprol than after iodixanol. %0 journal article %@ 0886-6236 %A Jung, M.,Vetter, M.,Herold, M.,Churkina, G.,Reichstein, M.,Zaehle, S.,Ciais, P.,Viovy, N.,Bondeau, A.,Chen, Y.,Trusilova, K.,Feser, F.,Heimann, M. %D 2007 %J Global Biogeochemical Cycles %N %P GB4021 %R doi:10.1029/2006GB002915 %T Uncertainties of modeling gross primary productivity over Europe: A systematic study on the effects of using different drivers and terrestrial biosphere models %U https://doi.org/10.1029/2006GB002915 %X Continental to global-scale modeling of the carbon cycle using process-based models is subject to large uncertainties. These uncertainties originate from the model structure and uncertainty in model forcing fields; however, little is known about their relative importance. A thorough understanding and quantification of uncertainties is necessary to correctly interpret carbon cycle simulations and guide further model developments. This study elucidates the effects of different state-of-the-art land cover and meteorological data set options and biosphere models on simulations of gross primary productivity (GPP) over Europe. The analysis is based on (1) three different process-oriented terrestrial biosphere models (Biome-BGC, LPJ, and Orchidee) driven with the same input data and one model (Biome-BGC) driven with (2) two different meteorological data sets (ECMWF and REMO), (3) three different land cover data sets (GLC2000, MODIS, and SYNMAP), and (4) three different spatial resolutions of the land cover (0.25° fractional, 0.25° dominant, and 0.5° dominant). We systematically investigate effects on the magnitude, spatial pattern, and interannual variation of GPP. While changing the land cover map or the spatial resolution has only little effect on the model outcomes, changing the meteorological drivers and especially the model results in substantial differences. Uncertainties of the meteorological forcings affect particularly strongly interannual variations of simulated GPP. By decomposing modeled GPP into their biophysical and ecophysiological components (absorbed photosynthetic active radiation (APAR) and radiation use efficiency (RUE), respectively) we show that differences of interannual GPP variations among models result primarily from differences of simulating RUE. Major discrepancies appear to be related to the feedback through the carbon-nitrogen interactions in one model (Biome-BGC) and water stress effects, besides the modeling of croplands. We suggest clarifying the role of nitrogen dynamics in future studies and revisiting currently applied concepts of carbon-water cycle interactions regarding the representation of canopy conductance and soil processes. %0 journal article %@ 0028-0836 %A Lendlein, A.,Hongyan, J.,Juenger, O.,Langer, R. %D 2005 %J Nature %N 7035 %P 879-882 %R doi:10.1038/nature03496 %T Light-induced shape-memory polymers %U https://doi.org/10.1038/nature03496 7035 %X Materials are said to show a shape-memory effect if they can be deformed and fixed into a temporary shape, and recover their original, permanent shape only on exposure to an external stimulus1, 2, 3. Shape-memory polymers have received increasing attention because of their scientific and technological significance4, 5. In principle, a thermally induced shape-memory effect can be activated by an increase in temperature (also obtained by heating on exposure to an electrical current6 or light illumination6, 7). Several papers have described light-induced changes in the shape of polymers8, 9, 10, 11, 12 and gels13, 14, 15, such as contraction8, 9, 10, bending11, 12, 13 or volume changes14, 15. Here we report that polymers containing cinnamic groups can be deformed and fixed into pre-determined shapes—such as (but not exclusively) elongated films and tubes, arches or spirals—by ultraviolet light illumination. These new shapes are stable for long time periods, even when heated to 50 °C, and they can recover their original shape at ambient temperatures when exposed to ultraviolet light of a different wavelength. The ability of polymers to form different pre-determined temporary shapes and subsequently recover their original shape at ambient temperatures by remote light activation could lead to a variety of potential medical and other applications. %0 journal article %@ 0232-1300 %A Jung, V.,Brokmeier, H.-G. %D 2000 %J Crystal Research and Technology %N %P 321-328 %T Magnetic Levitation Force of Bulk YBaCuO Pieces as a Function of Texture %U %X %0 journal article %@ 0730-3300 %A Jung, V.,Adam, M.,Bornemann, H.J.,Brokmeier, H.-G.,Kaiser, A.,Schnieber, R.,Thoms, J. %D 1999 %J Textures and Microstructures %N %P 125-138 %T Texture and magnetic levitation force of melt-textured YBaCuO-cylinders %U %X %0 conference lecture (invited) %@ %A Brokmeier, H.-G.,Jung, V. %D 1999 %J 2nd Eropean Conference on Neuton Scattering ECNS 99 %N %P %T Neutron texture analysis of bulk YBaCuO cylinders %U %X %0 conference lecture %@ %A Jung, V.,Brokmeier, H.-G.,Jansen, E.M.,Kaiser, A. %D 1999 %J Jahrestagung der Deutschen Gesellschaft fuer Kristallographie DGK 99 %N %P %T Verkippungen der c-Achsen und Verdrehungen um die c-Achsen in einem schmelztexturierten YBaCuO-Zylinder d Tiefenwirkung eines Saatkristalles %U %X %0 conference paper,conference lecture %@ %A Jung, V.,Brokmeier, H.-G.,Jansen, E.M.,Schnieber, R. %D 1999 %J Proceedings of ICOTOM 12 %N %P 523-528 %T Tilting of c-axes and twists around the c-axes in a melt-textured YBaCuO-cylinder %U %X %0 conference paper,conference lecture %@ %A Jung, V.,Adam, M.,Bornemann, H.J.,Brokmeier, H.-G.,Kaiser, A.,Schnieber, A. %D 1998 %J Jahrestagung der Deutschen Gesellschaft fuer Kristallographie, Zeitschrift fuer Kristallographie 1998, Supplement Issue %N %P 164 %T Die Reichweite einer ordnenden Wirkung eines in eine rekristallisierende YBaCuO-Schmelze implantierten Saatkristalles %U %X %0 journal article %@ 0255-5476 %A Jung, V.,Adam, M.,Bornemann, H.-J.,Brokmeier, H.-G.,Kaiser, A.,Schnieber, R. %D 1998 %J Materials Science Forum %N %P 595-600 %T Local Texture and Magnetic Levitation Force of YBaCuO Cylinders %U %X %0 report %@ %A Jung, V.,Adam, M.,Bornemann, H.-J.,Brokmeier, H.-G.,Kaiser, A.,Schnieber, R. %D 1998 %J %N %P %T The Influence of a Seed Crystal on the Texture of a Bulk YbaCuO Specimen %U %X %0 report %@ %A Jung, V.,Adam, M.,Bornemann, H. J.,Brokmeier, H.-G.,Kaiser, A.,Schnieber, R.,Thoms, J. %D 1997 %J %N %P %T Texture of Superconducting YBaCuO-Cylinders and their Levitation Force Repulsing an Inducting Permanent Magnet %U %X %0 conference paper,conference lecture %@ %A Jung, G.,Schossig-Tiedemann, M.,Kneifel, K. %D 1997 %J Book of Abstracts: Euromembrane '97 - Progress in Membrane Science and Technology; Third International Symposium %N %P 47-49 %T Is a Pressure Increase Method for Binary Gas Mixtures the Tool of Choise to Investigate Membranes for Air Dehydration %U %X %0 conference paper,conference lecture,GKSS report %@ %A Hornet, P.,Eripret, C.,Kocak, M.,Junghans, E. %D 1997 %J Second International Symposium on Mis-Matching of Interfaces and Welds: Performance of Strength Mis-Matched Welded or Bonded Joints %N %P 771-780 %T Performance of strength mis-match welded joints: comparison of experimental and numerical results %U %X %0 conference lecture %@ %A Junghans, E.,Schwalbe, K.-H. %D 1997 %J 29. Tagung DVM-Arbeitskreis Bruchvorgaenge; Bruchmechanische Bauteilbewertung: Verfahren, Regelwerke, Anwendungen %N %P %T Bewertung von reperaturgeschweissten Grosszugplatten mit dem ETM-MM %U %X %0 conference lecture %@ %A Kneifel, K.,Peinemann, K.-V.,Jung, G.,Schossig-Tiedemann, M. %D 1996 %J NAMS '96; 8th Annual Meeting of the North American Membrane Society %N %P %T Preparation of high-flux hollow fibre membranes for gas drying %U %X %0 conference paper,conference lecture,GKSS report %@ %A Junghans, E.,Kocak, M.,Schwalbe, K.-H. %D 1996 %J Proceedings of the 15th International Conference on Offshore Mechanics and Arctic Engineering (OMAE 1996) %N %P 383-392 %T Fracture behaviour of surface cracked wide plates of high strength steel containing overmatched repair welds %U %X %0 conference paper,conference lecture,GKSS report %@ %A Junghans, E.,Kocak, M.,Schwalbe, K.-H. %D 1996 %J ECF 11: Mechanisms and Mechanics of Damage and Failure; Proceedings of the 11th Biennial European Conference on Fracture %N 1 %P 2047-2054 %T Analysis of the fracture behaviour of surface cracked wide plates containing overmatching weld metal %U 1 %X %0 conference paper,conference lecture %@ %A Bornemann, H. J.,Brokmeier, H.-G.,Burghardt, T.,Hennig, W.,Jung, V.,Zink, U. %D 1996 %J Proceedings of ICOTOM 11 %N %P 951-956 %T Neutron texture measurement on solid YBaCuO specimen with a view to manufactoring a superconducting magnetic bearing %U %X %0 conference lecture %@ %A Kamusewitz, H.,Jung, G.,Paul, D. %D 1995 %J Potsdamer Workshop: Funktionalisierte Duenne Organische Schichten und Grenzflaechen; Abstracts %N %P %T Funktionalisierte Membrangrenzflaechen: Herstellung und Charakterisierung %U %X %0 conference paper,conference lecture,GKSS report %@ %A Kocak, M.,Junghans, E. %D 1994 %J Second European Conference on Joining Technology: EUROJOIN 2; Proceedings %N %P 259-270 %T Fracture toughness properties of similar and dissimilar electron beam welds %U %X %0 conference lecture %@ %A Thal, U.,Jung, G.,Kamusewitz, H. %D 1994 %J 5. Berliner Polymertage %N %P %T Charakterisierung von Membranoberflaechen %U %X %0 conference paper,conference lecture %@ %A Breuer, K.,Jung, T.,Friedrich, H.,Boin, M. %D 1991 %J MessComp '91: 5. Kongressmesse fuer industrielle Messtechnik; Conference Proceedings %N %P 244 %T A new method to test the adhesion in fibre reinforced materials and for coastings by sharing action %U %X