Multidimensional Polymer Characterization
Small and large degradation products of an AB copolymer network in a fibrous capsule five weeks after implantation (Hematoxylin and eosin stain). Photo: Hereon
Bio-Engineering represents the application of principles of engineering and natural sciences to tissues, cells, bioactive molecules, and biomaterials. Current research of the department aims at the development of cardiovascular devices, which gain rising importance in regenerative medicine. Small diameter vascular prosthesis, vascular patches, systems to occlude the left atrial appendage and polymer-based degradable drug-eluting stents are projects of primary interest.
Different strategies are applied in order to engineer hemocompatible implant surfaces and the research is focused on functionally-confluent and shear-resistant endothelialization of polymer-based surfaces. Moreover, functionalization of appropriate bulk materials with passivating substances e.g. poly (ethylene glycol) is performed to reduce protein adsorption and adhesion of blood cells.
Regeneration of the vessel wall is aimed to be supported by the developed devices, e.g. through drug eluting bioactive substances. According to their polarized profile blood vessels require prostheses which inhibit protein and cell contacts on the luminal surface (blood) but allow binding of cells on the abluminal surface so that the polymer prosthesis can integrate in the adjacent tissues.
Confocal laser scanning microscopic (CLSM) image of an endothelial cell culture after incubation with nanoparticles. Rhodamine B labelled nanoparticles (red), nuclei (blue), extracellular matrix protein fibronectin (green)/ scale bar represents 20 µm Photo: Hereon
The focus of the department BIE is with the biological evaluation of sterilized polymer-based biomaterials. Biocompatibility tests are based on the ISO 10993/5 with cell lines (L929), as well as with regio-specific primary cells (platelets, erythrocytes, monocytes, endothelial cells, smooth muscle cells and vascular fibroblasts) using static and dynamic 2D and 3D test systems. Acute or long-term studies with promising candidate materials are performed in small (histo- and hemocompatibility) and large animal models (functionality).
Phase contrast microscopic images of L929 mouse fibroblast cells after incubation with a cytocompatible (left) and cytotoxic (right) material/ scale bar represents 50 µm Photo: Hereon
Evaluation of the haemo- and histocompatibility of polymer systems – short or long-term absorbable implant materials or materials for extracorporeal applications – is an important field of work of the department. These materials have high potential for applications as scaffold and carrier materials for tissue engineering (TE) or as components of organ support systems and for the cultivation of specific cells and they are therefore important components of systems used in regenerative medicine.
In addition to cytological and molecular biological issues concerning toxicity/compatibility of the materials, concerning endothelialization of implants and concerning vessel formation (angiogenesis/vasculogenesis), the research is focusing on the development of cardiovascular implants e.g. such as small-diameter synthetic blood vessels, degradable stents, vessel or organ patches and on the development of innovative surgical devices such as suture materials.
Rasterelektronenmikroskopische Aufnahme von Fibrinpolymerisation auf einer thrombogenen Materialoberfläche/ Maßstabsbalken entspricht 5 µm. Photo: Hereon
The BIE department is conducting haemocompatibility studies to develop polymer materials for implants that are in contact with the bloodstream. To this end, the interaction of the materials specifically with thrombocytes, erythrocytes and leucocytes is being analysed, as are the complement activation, fibrin formation, fibrinolysis and contact activation.
The causes and effects in biological systems remain incompletely understood. Models of the interaction of biomaterials with the organism are therefore frequently introduced into the analysis. These models must be examined critically in the study of materials in the light of the respective investigation results. As such, e.g. the concepts concerning interactions of blood and its components with body-foreign surfaces are very strongly led by model concepts that are able to describe only inadequately the complex interactions between the reactive blood components, the buffer and electrolyte systems of the blood, and the exogenous materials. In the examination of new materials it is therefore fundamentally crucial to verify whether the existing model concepts are valid.
CLSM image of a primary cell coculture/ scale bar represents 200 µm Photo: Hereon
Specific statements in cell cultures can be made with primary cells that are obtained and established from the tissues into which the new materials are subsequently introduced. The establishment of such cultures is both difficult and relatively expensive but it is unavoidable due to the greater specificity and significance and for the planning and application of animal tests. Long-term studies in vitro, particularly on primary cultures, are necessary in order to be able to identify degradative effects on the newly investigated materials and on the interacting cells.
Brightfield image of a nitinol-based exostent (black) in the vein wall of a pig/ scale bar represents 500 µm Photo: Hereon
One major impediment to the development of histocompatible polymer-based biomaterials is inadequate understanding and lack of predictability of their degradation behaviour in the in vivo application. Today, however, it is clear that implants interact with the surrounding tissue and can therefore trigger a series of different reactions in their microenvironment. In order for implants to guarantee support or maintenance of impaired organ functions even in the long term, undesired reactions must be prevented as far as possible.