Growth factor release from vascular grafts

Abstract

The impregnation of vascular grafts with therapeutic agents contained with a controlled delivery vehicle and in a biologically active configuration can theoretically be of clinical value for purposes of either intra-arterial or intravenous drug delivery for systems applications or for local drug delivery for modifying the response of blood and/or the surrounding tissue to the implanted graft. Our laboratory has been interested primarily in local drug delivery by impregnating vascular grafts with factors designed to induce a spontaneous endothelialization and/or to inhibit smooth muscle cell proliferation. Fibroblast growth factor type I (FGF-I) and heparin (10 mg:250 U) placed into suspensions of fibrinogen polymerized by addition of thrombin promoted endothelial cell proliferation while suppressing smooth muscle cell proliferation in vitro. The kinetics of 125I-FGF-I release from grafts implanted into rabbit aortas was quantitated and irrespective of heparin concentration, grafts retained approximately 10% of the applied radiolabel at 1 week. Impregnated 60 μm internodal distance ePTFE grafts implanted into two canine models resulted in a transinterstitial ingrowth of capillary-rich mesenchymal tissue from the surrounding bed yielding near complete surface endothelialization by 1 month throughout 30 cm long bypass grafts. For purposes of systemic delivery, modifications of the fibrin glue preparation can significantly impact on the kinetics of growth factor release into circulation. It is likely that other therapeutic agents can be added to fibrin glue suspensions to achieve their systemic intravascular delivery.