Over 60,000 prosthetic grafts, which are comprised of either polyethylene terephthalate (polyester) or expanded polytetrafluoroethylene (ePTFE), are implanted in the United States each year. Medium (6-8mm) internal diameter (I.D.) prosthetic arterial grafts continue to have unacceptably high failure rates when used in the clinical setting. Currently, there is no small- diameter prosthetic arterial graft clinically accepted for use in the peripheral circulation (below knee popliteal) and coronary vessels, which affects over 500,000 patients each year. The two major complications associated with these grafts are acute thromboses and incomplete, unregulated cellular healing. This failure is attributed to the lack of endothelial cells at the biomaterial/blood interface, a lining that normal blood vessels possess. The goal of this two-year Phase I project is to synthesize and characterize in vitro a novel nanofibrous vascular graft material using our electrospinning and immobilization technology that would direct rapid adhesion and subsequent growth of circulating progenitor and more mature endothelial cells upon contact with the material. Our hypothesis is that immobilization of the endothelial-cell specific lectin Ulex europaeus-I (UEL-I) into the nanofibrous graft matrix will provide anchor sites in order to enhance cell-specific attachment and stabilize these cells the nanofibrous surface that will be under shear forces, thereby promoting cellular growth across the material surface. The specific objectives of this proposal are to: 1) synthesize a nanofibrous polyester material containing immobilized UEL-I (nEDA-UEL-I material), 2) evaluate physical properties of nEDA-UEL-I, 3) confirm binding site accessibility on nEDA-UEL-I, 4) assess UEL-I stability under simulated arterial flow conditions, 5) determine inherent UEL-I binding affinity for various cell types and 6) examine cell binding, retention and growth by nEDA-UEL-I. Development of a nanofibrous bioactive vascular graft would have a significant impact on small vessel repair and replacement. These grafts could be utilized in peripheral bypass (specifically below-knee) as well as for coronary artery bypass. Thus, the potential annual market value for an off-the-shelf synthetic small-diameter arterial bypass graft could exceed $1.5 billion. In Phase II, nEDA-UEL-I grafts will undergo acute and chronic implantation in an arterial grafting model in order to assess long-term patency and overall healing characteristics. Over 60,000 prosthetic grafts, which are comprised of either polyethylene terephthalate (polyester) or expanded polytetrafluoroethylene (ePTFE), are implanted in the United States each year. The two major complications associated with these grafts are acute thromboses and incomplete, unregulated cellular healing. This failure is attributed to the lack of endothelial cells at the biomaterial/blood interface, a lining that normal blood vessels possess. Development of a nanofibrous bioactive vascular graft that would direct appropriate cell adhesion and growth would have a significant impact on small vessel repair and replacement. Thus, the potential annual market value for an off-the-shelf synthetic small-diameter arterial bypass graft could exceed $1.5 billion. ? ? ?
