A Nanofibrous Biocomposite Small-Diameter Graft

描述（由申请人提供）： 临床上没有能够模拟正常动脉壁的生物学和物理特性的小直径（内径<5 mm）人造血管。这个为期两年的第一阶段项目的目标是联合不同的工业，生物医学和学术研究人员，利用静电纺丝技术在体外开发一种新型的纳米纤维生物活性小直径人工血管移植物。所得血管移植物将具有与自体动脉相当的生物学（抗血栓形成和促有丝分裂）和物理性质，从而改善移植物通畅性。我们的假设是，下一代人工动脉移植物必须具有多种结构和生物学特性，模拟天然动脉固有的一些过程，以防止血栓形成等并发症的发生。小直径纳米纤维生物复合材料血管移植物将由聚酯（涤纶）和胶原蛋白电纺而成，从而具有与天然动脉相似的特性。有效的抗凝血酶剂重组水蛭素（rHir）和内皮有丝分裂原血管内皮生长因子（VEGF）将共价结合到构建体内的胶原蛋白上。静电纺丝聚合物的弹性将提供周向顺应性，移植物壁内的薄编织涤纶网可防止扭结。具体目标是：1）开发用于涤纶/胶原复合移植物（ESDC）的静电纺丝方法，2）引入用于ESDC的新型内壁增强物，3）合成含有内壁增强物的新型小直径ESDC移植物，4）表征ESDC移植物的物理性质，5）将rHir和VEGF引入ESDC移植物，6）检查表面抗凝血酶性质，7）评估表面促有丝分裂性质和8）评估表面rHirNEGF在模拟动脉流条件下的稳定性。该项目的第二阶段将在犬颈动脉移植模型中评估这种新型ESDC-rHir- VEGF移植物。开发具有生物活性的小直径血管移植物将对小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以及冠状动脉旁路，在美国每年植入约500，000个移植物。潜在的，“现成的”合成冠状动脉旁路移植术的年市场价值可能超过15亿美元。

DESCRIPTION (provided by applicant): There is no small-diameter (< 5mm internal diameter) vascular prosthesis clinically available that is capable of emulating the biological and physical properties of the normal arterial wall. The goal of this two-year phase I project, which unites a diverse group of industrial, biomedical and academic researchers, is to develop in vitro a novel nanofibrous bioactive small-diameter prosthetic vascular graft using electrospinning technology. The resulting vascular graft would possess both biological (antithrombogenic and mitogenic) and physical properties comparable to that of native artery, thereby improving graft patency. 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. A small-diameter nanofibrous biocomposite vascular graft will be electrospin from polyester (Dacron) and collagen, thereby possessing properties similar those of native artery. The potent antithrombin agent recombinant hirudin (rHir) and endothelial mitogen vascular endothelial growth factor (VEGF) will be covalently bound to collagen within the construct. The elastic properties of the electrospin polymer will provide circumferential compliance, with kink-resistance prevented by a thin braided Dacron mesh within the graft wall. The specific objectives are to: 1) develop electrospinning methodology for a Dacron/collagen composite graft (ESDC), 2) incorporate novel inner-wall reinforcement for ESDC, 3) synthesize novel small-diameter ESDC graft containing inner-wall reinforcement, 4) characterize physical properties of ESDC graft, 5) immobilize rHir and VEGF to ESDC graft, 6) examine surface antithrombin properties, 7) evaluate surface mitogenic properties and 8) assess surface rHirNEGF stability under simulated arterial flow conditions. Phase II of this project will evaluate this novel ESDC-rHir- VEGF graft in a canine carotid grafting model. 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 coronary artery bypass graft could exceed $1.5 billion.