EnCoMed- Enzymatic Functionalization of Collagens for Medical Applications

Project: Research project

Description

Collagen is a very popular biomaterial for biomedical applications where it is widely used to
produce drug delivery systems or scaffolds for cellular growth and tissue engineering. However,
the application of collagen-based materials is limited by their lack of mechanical and thermal
stability. To overcome these problems collagen-based materials are functionalized or crosslinked
by using chemical agents. Although these treatments are quite effective, the chemical
reagents comprise residue problems with potential or well known toxicity. That is why in the
medical field there is a high need for novel functionalizing and cross-linking mechanisms.
Functionalization of collagen using enzymatic procedures offers a promising alternative. It has
been shown that treatment with enzymes such as transglutaminase, laccase or tyrosinase leads
to cross-linking preferably of unfolded collagen helical structures. Such materials provide
adequate support and sustainability for porous collagen systems to be used in cell cultivation or
wound healing. Furthermore, they offer great potential for sustained release of incorporated
molecules. To provide an adequate drug liberation profile from collagen materials for several
weeks upon parenteral application, dense matrices are necessary. These can be obtained, e. g.
by extrusion or electrospinning. In this study, the electrospinning process will be used to make
collagen-based non-woven nanostructures which mimic the extracellular matrix and enhance cell
growth only by their architecture. To reinforce these structures for final applications and to
provide a 3 D architecture, knitted bioresorbable scaffolds will be used to host the electrospun
materials.
Another major benefit of enzymatic cross-linking is its enormous potential to introduce not only
cross-links but at the same time add specific features by co-immobilizing compounds, particularly
cytokines. This innovative design of collagen materials will be evaluated during the project by
applying two different setups. The first one is collagen equipped with covalently attached
endothelial growth factor (VEGF) which is of interest, e. g. for coating of vascular grafts. The
effect of this material on endothelial cells as well as smooth muscle cells will be evaluated. The
second realization is collagen enriched with bone morphogenetic protein (BMP). This material
and its manufacturing process will be based on the experience gained with the VEGFinvestigations.
After transferring it into porous systems for bone regeneration, the BMP-collagen
composite material will be tested for differentiation of fibroblasts.
In summary, the aim of this precompetitive project is to develop new methods for the enzymatic
functionalization of native collagen structures and to use these structures as drug delivery
systems.
StatusFinished
Effective start/end date1/10/1130/09/13