Small-diameter vascular prostheses which release bioactive agents

The need for small-diameter vascular prostheses has been well documented by clinical experience which has shown poor graft patency rate; with prostheses-less than 6 mm internal diameter. Recently, substances which show considerable ability to stimulate endothelial cell proliferation in both capillaries and large vessels have been isolated and purified from a variety of tissues. It may be hypothesized that incorporating these substances into biocompatible materials could enhance endothelial cell development when these materials are used for fabrication of vascular prostheses. We have developed a spraying-phase inversion process which allows solutions of synthetic polymers or suspensions of synthetic and natural polymers to be blended and deposited over a rotating mandrel. With this method we have fabricated 1.5 mm ID, porous, compliant polyurethane-tubes which incorporate and release basic fibroblast growth factor (bFGF). In vitro releasing studies were performed using 10% albumin by weight as carrier and which demonstrated l-2 ng/cm/graft/day rate of release of bFGF. The mitogenic effect of released bFGF was tested by incubating 1 cm long pieces of tubing with human endothelial cells seeded at low density (40 cells/mm2) in vitro and using a culture medium without any growth factors added. The [3H] thymidine uptake by the cells was measured. After 3 days, the cells incubated with tubing that did not contain bFGF did not proliferate to any extent. Cells incubated with tubing that did contain bFGF continued to proliferate actively. The results of these experiments have shown that a bioactive bFGF can be released from vascular prostheses. Release of factors such as bFGF may enhance the early development of confluent endothelial surfaces in vivo that may increase thromboresistance of vascular prostheses.