VascuTrap

The aim of this project is to develop a biofunctionalized vascular implant with reduced thrombogenicity. A bioactivity of this implant should be achieved by two surface modifications. 1) An innovative cross-linked biomaterial coating is to be applied to the implant. 2) A recombinant capture protein is to be introduced into this coating, which specifically binds endothelial progenitor cells from the bloodstream and thus induces increased endothelialization of the implant.

Bioactive vascular implants are to be developed as part of the VascuTrap project. The luminal surface of synthetic vessels is to be coated with a highly specific capture protein that binds stem cells circulating from the bloodstream, more precisely vascular progenitor cells (EPC), so that very rapid natural and thus antithrombogenic cell colonization is achieved for better tolerability of the synthetic vessel. The capture protein is attached to a specially reactive, biomaterial-based thin layer on the vessel material. The scavenger protein is directed against an EPC-specific protein, so that only endothelial progenitor cells are selectively recruited from the large number of blood cells.

In order to achieve this goal, three components (synthetic vessels, a reactive thin layer and a highly specific capture protein) are to be combined into a new type of implant in an interdisciplinary approach.

Approved standard implants of different diameters made of non-resorbable polymers/block copolymers are used as synthetic blood vessels. The polymers are biocompatible and are made from either unitary membranes or interwoven polymer threads. Subsequent process steps are used to test surface modifications that enable the capture protein to be attached.

The highly specific capture protein is an antibody against cell surface protein. This protein is only expressed on blood endothelial progenitor cells (EPC), but not on other blood cells. Accordingly, EPCs can be enriched very selectively and efficiently from the large number of blood cells using a high-affinity monoclonal antibody, whereupon the progenitor cells differentiate into endothelial cells. The antibody is generated using a patented process in which vectors containing the gene for the target protein are administered intracutaneously to rats.

The individual components and, above all, their combination into a bioactive implant are examined on two levels for their biological effectiveness, both cell-biologically in vitro (NMI) and preclinically in animal experiments (University Hospital Tübingen).

The cell biological in vitro profiling of the modified vessels and their individual components is tested quantitatively and qualitatively using a variety of cell culture methods. Measurement parameters are biocompatibility, specific versus non-specific cell adherence, proliferation, migration and differentiation.