Clinical experience with vascular grafts has demonstrated poor patency rates when currently available synthetic materials are used in prosthese less than 6 mm in diameter. Autologous saphenous veins and internal mammary arteries are now considered the small diameter grafts of choice for peripheral and cardiovascular applications, however, in many cases these vessels have been used previously or are of unsuitable quality, forcing surgeons to use prostheses and materials associated with a high probability of graft thrombosis. In an effort to address this problem, other investigators have demonstrated that prostheses fabricated from suitable porous or microporous materials are penetrated by host cells which appear to be associated with the formation of a cellular lining or """"""""neointima"""""""" on the luminal surface of the graft. Recent experience in experimental animals has indicated that long term graft patency (one month to several years) is enhanced by the establishment of a stable and mature neointima which ideally consists of well differentiated endothelial and smooth muscle cells with a minimum of fibroblasts, collagen production, and inflammatory reaction. Many factors related to the prosthesis including specific chemical properties, compliance, bioresorbability, and weak fixed electric charge have been investigated for their possible roles in promoting appropriate neointima formation and in discouraging early erythrocyte adhesion and graft thrombosis. However, no investigation to date has evaluated the effect of transient electric charge, such as that obtained with piezoelectric materials, on these parameters of vascular grafts performance. Pulsed electromagnetic fields generated by piezoelectric prostheses or from external devices have been shown to enhance osteogenic bone repair, nerve regeneration, and wound healing. Further, previous investigators have demonstrated that manipulation of the electric charge on the luminal surface of vascular prostheses may be valuable for inhibiting blood component adhesion to the material and the initiation of the clotting cascade. Pulsed electric charges developed by piezoelectric grafts may then have the double advantage of discouraging early platelet adhesion and thrombosis and at the same time enhancing the development of a stable, mature, nonthrombogenic neointima in a porous or microporous graft. Our laboratory has recently developed a technique for fabricating flexible, biocompatible, microporous tubes suitable for use as microvascular prostheses (1-4 mm ID) from a 7:3 copolymer of trifluoroethylene-polyvinylidine fluoride (P(VDF-TrFE)). These prostheses can be electrically poled in our laboratory yielding prostheses with pure dipole related piezoelectric activity which show measured transmural charges in the range of 80-180 picoCoulombs (pC) per millimeter deflection. The tubes can also be left unpoled and used as control grafts with identical chemical composition and mechanical properties but without piezoelectric activity. The research proposed in this application will entail 3 tasks: (1) fabrication and (2) piezoelectric characterization of 1.5 mm ID microvascular prostheses in both the poled and unpoled control form, and (3) evaluation of platelet adhesion, mural thrombus formation, patency, and neointima development using the prostheses in the rat abdominal aorta model.
