A Nanofibrous Biocomposite Small-Diameter Graft

纳米纤维生物复合材料小直径移植物

• 批准号: 7106506
• 负责人: Matthew Douglas Phaneuf
• 金额: $ 37.5万
• 依托单位: BIOSURFACES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7106506
• 关键词: artery; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotechnology; blood vessel prosthesis; collagen; dogs; hirudins; medical implant science; nanotechnology; polyethylenes; small molecule; tensile strength; tissue engineering; vascular endothelial growth factors

DESCRIPTION (provided by applicant): There is no small-diameter (< 5mm internal diameter) vascular prosthesis approved for clinical use in small vessel reconstruction. Current prostheses are not capable of emulating the biological and physical properties of the normal arterial wall, resulting in high failure rates. In phase I, a nanofibrous biocomposite small-diameter vascular graft comprised of Dacron and Type IV collagen (ESDC) was synthesized, with kinkresistance created within the graft structure. This novel thin-walled graft had minimal water permeation and excellent physical properties. The potent antithrombin agent recombinant hirudin (rHir) and endothelial cellspecific mitogen Vascular Endothelial Growth Factor (VEGF) were then covalently bound to the ESDC surface (ESDC-rHir-VEGF). These surface bound agents were biologically active as determined via specific in vitro assays and showed stability under simulated arterial flow conditions. Lastly, the ESDC graft showed excellent handling characteristics when implanted into a canine femoral artery in a preliminary in vivo evaluation of the graft. The goal of this Phase II proposal is to assess blood permeation and graft patency/healing of the ESDC-rHir-VEGF graft using a canine arterial grafting model. Our hypothesis is that the next generation of prosthetic arterial grafts will have to possess multiple structural and biological properties that mimic some of those processes inherent to native arteries in order to prevent complications such as thrombosis from occurring. The specific objectives of Phase II are to: 1) synthesize ESDC vascular grafts for implantation studies, 2) develop an automated graft synthesis process, 3) evaluate physical and chemical properties of the ESDC graft, 4) covalently immobilize rHir and VEGF to ESDC surface, 5) assess in vivo acute and chronic implantation periods, and 6) examine macroscopically/microscopically explanted grafts. Phase III of this project will continue long-term assessment of this novel ESDC-rHir-VEGF graft in the canine femoral arterial grafting model employed in Phase II. Development of a bioactive small-diameter vascular graft would have a significant impact on small vessel repair and replacement. These grafts could be utilized in peripheral bypass as well as for coronary artery bypass, which have some 500,000 grafts implanted annually in the United States. Potentially, the annual market value for an "off-the-shelf" synthetic arterial bypass graft could exceed $1.5 billion.

描述(由申请人提供)： 目前尚无小直径(内径5 mm)血管假体被批准用于小血管重建。目前的假体不能模拟正常动脉壁的生物和物理特性，导致高失败率。在第一阶段，合成了一种由涤纶和IV型胶原(ESDC)组成的纳米纤维生物复合材料小直径血管移植物，在移植物结构中产生了抗扭结。这种新型薄壁接枝具有最小的水渗透率和良好的物理性能。然后，将有效的抗凝血酶药物重组水飞蓟素(RHir)和内皮细胞特异性有丝分裂原血管内皮生长因子(VEGF)共价结合到ESDC表面(ESDC-rHir-VEGF)。通过体外实验确定这些表面结合剂具有生物活性，并在模拟动脉血流条件下表现出稳定性。最后，在初步的体内评估中，ESDC移植物在植入犬股动脉后表现出良好的操控性。此二期方案的目标是使用犬动脉移植模型评估ESDC-rHir-VEGF移植物的血液渗透和移植物开放/愈合。我们的假设是，为了防止血栓等并发症的发生，下一代人造动脉移植物将必须具有多种结构和生物学特性，以模拟某些天然动脉固有的过程。第二阶段的具体目标是：1)合成用于植入研究的ESDC血管移植物，2)开发自动化的移植物合成过程，3)评估ESDC移植物的物理和化学性质，4)将rHir和VEGF共价固定在ESDC表面，5)评估体内急性和慢性植入期，以及6)从宏观和微观上检查移植的移植物。该项目的第三阶段将继续在第二阶段采用的犬股动脉移植模型中对这种新型ESDC-rHir-VEGF移植物进行长期评估。开发具有生物活性的小直径血管移植物将对小血管的修复和替换产生重大影响。这些移植物可用于外周搭桥术和冠状动脉搭桥术，美国每年约有50万例移植物植入。潜在地，“现成”合成动脉搭桥术的年市场价值可能超过15亿美元。