Endothelialization of ePTFE Small Diameter Vascular Grafts

描述（由申请人提供）： ePTFE小直径血管移植物的内皮化摘要在解决对可行的小直径血管移植物（i.d. <5 mm），我们建议开发一种新型氟碳表面活性剂聚合物涂层，以实现在膨胀型聚四氟乙烯（ePTFE）小直径血管移植物上的快速体内内皮化，而无需EC预接种。碳氟表面活性剂聚合物由内皮细胞（EC）特异性肽，寡糖和碳氟化合物分支沿着聚（乙烯胺）骨架。EC特异性，但不是血小板特异性，在聚合物中的肽被设计为促进控制EC附着，增殖，剪切稳定性和功能;葡聚糖寡糖被设计为抑制血小板粘附和血栓形成;和氟碳分支被设计为在ePTFE表面上进行表面诱导组装。具体而言，我们建议：1）制备组装在ePTFE表面上的EC特异性表面活性剂聚合物; 2）测定表面活性剂聚合物改性的ePTFE上的体外EC行为和EC/血小板竞争;和3）评价ePTFE移植物上的体外EC附着、增殖和长期粘附。EC特异性CRRETAWAC和葡聚糖寡糖将被纳入表面活性剂聚合物和表面修饰将通过灵敏的光谱和物理方法进行表征。将评价EC随时间的附着、增殖和迁移。通过旋转圆盘实验研究了内皮细胞的剪切稳定性。将测量EC止血功能（前列环素和tPA的产生）。竞争EC/血小板粘附将进行研究，以优化表面活性剂的结构。将使用体外灌注系统研究EC在涂层ePTFE移植物上的附着、增殖和粘附，持续时间较长（最长5天）。从这些研究中，我们将确定肽与葡聚糖在促进内皮化而不刺激血栓形成方面的最佳比例。我们预计该项目将导致ePTFE小直径血管移植物的高效体内内皮化。 公共卫生相关性： 由于心血管疾病的广泛存在，临床上迫切需要一种功能性小直径人造血管来治疗动脉粥样硬化性血管疾病。本研究的主要目标是开发一种即植入型小直径膨胀型聚四氟乙烯（ePTFE）血管移植物，该血管移植物可促进体内内皮细胞（EC）附着和生长，而无需EC预接种。

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.