Endothelialization of ePTFE Small Diameter Vascular Grafts

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DESCRIPTION (provided by applicant): Endothelialization of ePTFE Small Diameter Vascular Grafts Abstract In addressing the urgent clinical need for an viable small diameter vascular graft (i.d.<5mm), we propose to develop a novel fluorocarbon surfactant polymer coating to achieve rapid in vivo endothelialization on expanded polytetrafluoroethylene (ePTFE) small diameter vascular grafts without the need for EC pre-seeding. The fluorocarbon surfactant polymer consists of endothelial cell (EC)-specific peptides, oligosaccharides and fluorocarbon branches along the poly (vinyl amine) backbone. EC-specific, but not platelet-specific, peptides in the polymer are designed to facilitate control of EC attachment, proliferation, shear stability, and functions; dextran oligosaccharides are designed to suppress platelet adhesion and thrombus formation; and the fluorocarbon branches are designed to undergo surface-induced assembly on the ePTFE surface. Specifically, we propose to: 1) prepare EC-specific surfactant polymers that assemble on ePTFE surface; 2) Determine the in vitro EC behavior and EC/platelet competition on surfactant polymer modified ePTFE; and 3) Evaluate the in vitro EC attachment, proliferation, and long-term adhesion on ePTFE graft. EC-specific CRRETAWAC and dextran oligosaccharides will be incorporated into surfactant polymers and surface modifications will be characterized by sensitive spectroscopic and physical methods. EC attachment, proliferation and migration over time will be evaluated. Shear stability of ECs will be investigated with rotating disk experiment. EC hemostatic functions (production of prostacyclin and tPA) will be measured. Competitive EC/platelet adhesion will be studied to optimize the surfactant structure. An in vitro perfusion system will be used to study EC attachment, proliferation and adhesion on the coated ePTFE graft over extended period of time (up to 5 days). From these studies, we shall determine the optimum ratio of the peptide to dextran in promoting endothelialization without stimulating thrombosis. We anticipate this project will lead to highly effective in vivo endothelialization of ePTFE small diameter vascular grafts. PUBLIC HEALTH RELEVANCE: There is an urgent clinical need for a functional small diameter vascular prosthesis to treat atherosclerotic vascular disease due to the widespread of cardiovascular disorders. The main goal of this research is to develop a ready-to-implant small diameter expanded polytetrafluoroethylene (ePTFE) vascular graft that facilitates in vivo endothelial cell (EC) attachment and growth without the need for EC pre-seeding.