A Bioactive Prosthetic Vascular Graft

生物活性人工血管移植物

• 批准号: 7393600
• 负责人: Matthew Douglas Phaneuf
• 金额: $ 10万
• 依托单位: BIOSURFACES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7393600
• 关键词: Acute; Adherence; Affinity; Anticoagulants; Antithrombins; Arteries; Bilateral; Binding; Biocompatible; Biological Assay; Biological Testing; Blood; Bypass; Caliber; Canis familiaris; Cell Survival; Cell-Matrix Junction; Cells; Characteristics; Chronic; Clinical; Condition; Coronary Artery Bypass; Data Analyses; Development; Devices; Economics; Endothelial Cells; Endothelium; Evaluation; Failure; Goals; Grant; Growth; Healed; Immobilization; Implant; In Vitro; Knee; Ligands; Localized; Marketing; Modeling; Peripheral; Phase; Platelet Activation; Play; Polyesters; Polyethylene Terephthalates; Polytetrafluoroethylene; Principal Investigator; Proliferating; Property; Prosthesis; Protein C; Proteins; Rate; Reaction; Role; Signal Transduction; Simulate; Site; Small Business Technology Transfer Research; Structure; Surface; Thrombin; Thrombosis; Thrombus; Transplanted tissue; United States; Vascular Graft; Veins; Whole Blood; activated Protein C; chemical property; dacron; design; functional group; healing; novel; prevent; receptor binding; repaired

DESCRIPTION (provided by applicant): 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) and small (<5mm) internal diameter (I.D.) prosthetic arterial grafts continue to have unacceptably high failure rates when used in the clinical setting. The two major complications associated with these grafts are acute thromboses and incomplete, unregulated cellular healing. The goal of this Phase I STTR grant is to develop in vitro a novel polyester vascular graft with a bioactive surface. Our hypothesis is covalent immobilization of Activated Protein C (APC), a natural anticoagulant, onto a functionalized polyester vascular graft surface will prevent surface thrombus formation via renewably inactivating FVa and FVIIIa and by preventing platelet activation. Additionally, surface bound APC would promote adherence of EPCR positive cells circulating in the blood to the polyester graft surface through a highly specific, high affinity ligand-receptor binding reaction and signal graft-adherent cells or cells from adjacent endothelium to proliferate and migrate on the surface. The specific objectives of this study are to: 1) optimize surface functional groups on the modified polyester (EDA) graft surface and immobilize APC, 2) evaluate the biostability of surface bound APC and 3) biological testing of surface immobilized APC. Development of a bioactive polyester vascular graft that would provide localized surface antithrombin properties and stimulate endothelial cell specific attachment would have a significant impact on vessel repair and replacement. These grafts could be utilized in peripheral bypass (specifically below-knee) as well as for coronary artery bypass, in which there are over 500,000 bypass grafts implanted annually in the United States. Thus, the potential annual market value for an off-the-shelf bioactive synthetic arterial bypass graft could exceed $1.5 billion. In Phase II of this proposal, EDA-APC grafts (6mm internal diameter) with covalently bound APC will undergo acute and chronic evaluation in a canine bilateral carotid grafting model in order to assess long-term patency and overall healing characteristics.

描述（由申请人提供）：每年在美国植入超过60，000件由聚对苯二甲酸乙二醇酯（聚酯）或膨胀型聚四氟乙烯（ePTFE）组成的假体移植物。中等（6- 8 mm）和小（<5 mm）内径（I.D.）当用于临床环境时，人工动脉移植物仍然具有不可接受的高失败率。与这些移植物相关的两个主要并发症是急性血栓形成和不完全、不受调节的细胞愈合。该一期STTR资助的目标是在体外开发一种具有生物活性表面的新型聚酯血管移植物。我们的假设是将活化蛋白C（APC）（一种天然抗凝剂）共价固定到官能化聚酯血管移植物表面上将通过可再生地灭活FVa和FVIIIa以及通过防止血小板活化来防止表面血栓形成。此外，表面结合的APC将通过高度特异性、高亲和力的配体-受体结合反应促进血液中循环的EPCR阳性细胞粘附到聚酯移植物表面，并向移植物粘附细胞或来自相邻内皮的细胞发出信号以在表面上增殖和迁移。本研究的具体目标是：1）优化改性聚酯（EDA）接枝物表面的表面官能团和表面固定的APC，2）评价表面结合的APC的生物稳定性和3）表面固定的APC的生物测试。开发一种生物活性聚酯血管移植物，提供局部表面抗凝血酶特性，刺激内皮细胞特异性附着，将对血管修复和置换产生重大影响。这些移植物可用于外周旁路（特别是膝下）以及冠状动脉旁路，其中在美国每年植入超过500，000个旁路移植物。因此，现成的生物活性合成动脉旁路移植物的潜在年市场价值可能超过15亿美元。在该提案的第II阶段，将在犬双侧颈动脉移植模型中对具有共价结合APC的EDA-APC移植物（内径6 mm）进行急性和慢性评价，以评估长期通畅性和总体愈合特征。