No adequate small diameter vascular prostheses are now commerically available, with the major reasons for loss of patency being thrombus formation and neointimal fibrous hyperplasia. Also, grafts are often the site of chronic infections. This proposed feasibility study expects to improve the biocompatibility of commerically available vascular implant polymers by selectively immobilizing extracellular matrix proteins and growth factors to promote endothelial cell overgrowth of the graft luminal surface (to produce superior blood compatibility) and smooth muscle growth in the graft matrix and on the outer surface (to produce added strength and resiliency). Antibiotics and antithrombic agents will also be immobilized to prevent thrombus formation and bacterial growth during the period of cell overgrowth. Appropriate in vitro assays will be conducted to determine optimum concentrations that selectively promote endothelial or smooth muscle overgrowth, inhibit thrombus formation, and inhibit bacterial growth. A consortium arrangement has been made to conduct preliminary in vivo implant studies in Phase I and extensive implant studies in Phase II. Proof-of-concept of this technology should allow the development of vascular implants with improved blood compatibility and reduced problems with infections.
