Endothelialization of ePTFE Small Diameter Vascular Grafts

ePTFE 小直径血管移植物的内皮化

• 批准号: 7805303
• 负责人: SHUWU WANG
• 金额: $ 10.58万
• 依托单位: NANOMIMETICS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7805303
• 关键词: Address; Adhesions; Affinity; Amines; Atherosclerosis; Binding; Blood Platelets; Blood Vessel Prosthesis; Caliber; Cardiovascular Diseases; Cell physiology; Cell-Matrix Junction; Cells; Clinical; Development; Dextrans; Endothelial Cells; Engineering; Exhibits; Expanded PTFE; Fluorocarbons; Goals; Growth; Hemostatic function; Hyperplasia; Implant; In Vitro; Lead; Measures; Methods; Modification; Oligosaccharides; Oxygen; Peptides; Perfusion; Physiological; Polymers; Polytetrafluoroethylene; Production; Proliferating; Prostaglandins I; Research; Specificity; Structure; Surface; System; Thrombosis; Thrombus; Time; Vascular Graft; Vertebral column; Water; abstracting; base; cell behavior; design; dextran; in vitro testing; in vivo; migration; novel; public health relevance; research study; surfactant

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.

描述（由申请人提供）： ePTFE 小直径血管移植物的内皮化 摘要 为了满足临床对可行的小直径血管移植物（内径<5mm）的迫切需求，我们建议开发一种新型氟碳表面活性剂聚合物涂层，以在膨胀聚四氟乙烯（ePTFE）小血管上实现体内快速内皮化。直径血管移植物，无需 EC 预播种。氟碳表面活性剂聚合物由内皮细胞 (EC) 特异性肽、寡糖和沿着聚（乙烯胺）主链的氟碳分支组成。聚合物中的 EC 特异性肽（而非血小板特异性肽）旨在促进控制 EC 附着、增殖、剪切稳定性和功能；葡聚糖寡糖旨在抑制血小板粘附和血栓形成；碳氟化合物分支被设计为在 ePTFE 表面上进行表面诱导组装。具体来说，我们建议：1）制备在 ePTFE 表面组装的 EC 特异性表面活性剂聚合物； 2) 确定表面活性剂聚合物改性 ePTFE 的体外 EC 行为和 EC/血小板竞争； 3) 评估体外 EC 在 ePTFE 移植物上的附着、增殖和长期粘附。 EC 特定的 CRRETAWAC 和葡聚糖寡糖将被纳入表面活性剂聚合物中，并且表面改性将通过敏感的光谱和物理方法进行表征。将评估 EC 随时间的附着、增殖和迁移。 EC 的剪切稳定性将通过转盘实验进行研究。将测量 EC 止血功能（前列环素和 tPA 的产生）。将研究竞争性 EC/血小板粘附，以优化表面​​活性剂结构。体外灌注系统将用于研究 EC 在较长时间内（最多 5 天）在涂层 ePTFE 移植物上的附着、增殖和粘附。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。我们预计该项目将实现 ePTFE 小直径血管移植物的高效体内内皮化。 公共卫生相关性： 由于心血管疾病的普遍存在，临床迫切需要一种功能性小直径血管假体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可立即植入的小直径膨体聚四氟乙烯 (ePTFE) 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。