A Novel Electrospun Vascular Graft

描述(由申请人提供)：一种新型的磺化聚合物具有独特的化学可裁剪特性和加工特性，已显示出作为抗血栓表面的巨大前景，并已被证明是一种有效的中性粒细胞衍生蛋白水解酶的抑制剂。第一阶段的SBIR测试被建议用来研究这种聚合物作为血管移植材料的混合物。这项拟议研究的主要具体目标包括利用静电纺丝技术从这些材料制造第一代血管移植物，并研究在血液流动下移植物的性能。其主要目标是将血小板黏附和活化降至最低。这种创新和合理的抗血栓血液管道方法是建立在几项不同研究的基础上，这些研究揭示了这种聚合物家族具有良好的生物应用属性。这一第一阶段SBIR的最终目标是开发和鉴定一种固有的非血栓形成和抗炎的水凝胶(混合)表面，具有作为血管移植物和其他救命心血管设备的潜在应用。 公共卫生相关性：心血管疾病(CVD)是美国男性和女性死亡和残疾的主要原因，目前影响着7000多万美国人。总体而言，每年有600多万人因治疗心血管疾病而住院。因此，心血管疾病对我国医疗保健系统的经济影响持续增长，特别是随着人口老龄化。2006年心脏病和中风的成本(美国)超过4000亿美元，其中包括医疗成本支出以及死亡和残疾造成的生产力损失。在心血管疾病的范畴下，动脉粥样硬化导致的外周动脉疾病(PAD)、冠状动脉疾病(CAD)和脑血管疾病都是由血管狭窄(狭窄)和/或闭塞的原发事件引起的，这些事件是由于血栓形成的失调以及与之相关的炎症事件，包括平滑肌细胞(SMC)的渗透、新生内膜增殖和不适应性血管重构。狭窄和闭塞导致顺行血流量减少/丧失。对于PAD，这可能会导致周围肢体的跛行和组织病变，而对于CAD，这可能会导致缺血，通常是致命的心肌梗死，对于脑血管情况，这可能会导致中风。介入血管内和/或外科治疗以清除血栓和重建血管血流对于这些疾病的临床治疗是必要的。血管内治疗包括机械方法，如导管介导的血管成形术、冷冻成形术和血管内膜切开术，以及药物治疗方法，如经导管输送溶栓、抗血小板和抗增殖药物。这些方法通常与支架植入术相结合。近年来，药物洗脱支架(DES)得到了发展，在金属支架表面涂覆一层载药聚合物基质，用于治疗药物的持续释放。手术方法包括搭桥术，其中许多是由合成聚合物(例如ePTFE)制成的。对于其他心血管疾病，生物材料也发挥着重要作用。使用的设备包括起搏器、心室辅助设备和全人工心脏。所有上述设备都依赖于与流动的血液接触的合成材料。这些材料容易导致蛋白质(如纤维蛋白原、纤维蛋白)快速沉积、变性以及随后的血小板黏附和激活，可能导致凝块形成和随后的凝血和炎症事件的激活。反过来，材料性能可能会受到影响，需要反复进行血管内或外科手术。因此，这些患者通常需要永久抗凝治疗，以防止中风和/或设备故障。因此，如上所述，设备上的抗蛋白质和抗血小板血液接触接口可以改善患者的预后，降低总体护理成本。第一代人造血管移植物是我们研究的对象。这些研究中的聚合物组合物是磺化嵌段共聚聚合物共混物，具有低凝血性、良好的(湿)机械性能，并且可以静电纺丝成三维血管移植物。电纺接枝(在流动下)的动态研究将用于了解材料在血液中的行为。

DESCRIPTION (provided by applicant): A novel sulfonated polymer with unique chemically tailorable properties and processing characteristics has shown considerable promise as a thrombo- resistant surface and has been proven to be an effective inhibitor against neutrophil-derived proteases. Phase 1 SBIR testing is proposed to investigate blends of this polymer as vascular graft material. The major specific aims of the proposed research involve the fabrication of a first generation vascular graft from these materials using an electrospinning technique and investigating the performance of the graft with blood under flow. The primary objective is to minimize platelet adhesion and activation. This innovative and rational approach to a thrombo-resistant blood conduit is founded on the basis of several different studies that have revealed promising bioapplicable attributes of this polymer family. The end-goal of this Phase 1 SBIR is to develop and identify an inherently non-thrombogenic and anti-inflammatory hydrogel (blend) surface with potential application as a vascular graft and other lifesaving cardiovascular devices. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the leading cause of death and disability for both men and women in the U.S., presently affecting more than 70 million Americans. Overall, more than 6 million hospitalizations occur each year for treatment of cardiovascular diseases. Consequently, the economic impact of CVD on our nation's health care system continues to grow, especially as the population ages. The cost of heart disease and stroke in 2006 (U.S.) was greater than $400 billion, when healthcare cost expenditures and lost productivity from death and disability are accounted for. Under the umbrella of cardiovascular diseases, atherosclerosis-induced peripheral artery disease (PAD), coronary artery disease (CAD) and cerebrovascular disease all result from the primary event of vessel narrowing (stenosis) and/or occlusion due to dysregulated formation of clots and associated inflammatory events involving smooth muscle cell (SMC) infiltration, neointimal proliferation and maladaptive vascular remodeling. Stenosis and occlusion lead to reduction/loss of antegrade blood flow. For PAD, this may lead to claudication and tissue morbidity of peripheral extremities, while for CAD this can lead to ischemia and often fatal myocardial infarction and, for cerebrovascular situations, this may lead to stroke. Interventional endovascular and/or surgical treatment to remove thrombus and to reestablish vascular flow is necessary for clinical management of these diseases. Endovascular treatments involve mechanical approaches like catheter-mediated angioplasty, cryoplasty and enderactomy and, pharmacotherapeutic approaches like transcatheter delivery of thrombolytic, anti-platelet and anti-proliferative drugs. Often these approaches are combined with stenting. Recent years have seen the development of drug eluting stents (DES) where the metal stent surface is coated with a drug-loaded polymer matrix for sustained release of therapeutic agents. Surgical approaches involve bypass grafts, many of which are made of synthetic polymers (e.g. ePTFE). For other cardiovascular diseases biomaterials also play an important role. Devices including pacemakers, ventricular assist devices, and the total artificial heart are used. All of the aforementioned devices depend upon synthetic materials that come into contact with flowing blood. These materials are prone to rapid protein (e.g. fibrinogen, fibrin) deposition, denaturation and subsequent adhesion and activation of blood platelets potentially leading to clot formation and the subsequent activation of coagulation and inflammatory events. In turn, material performance can be compromised necessitating recurring endovascular or surgical procedures. As such, these patients generally require perpetual anticoagulation therapy in order to prevent stroke and/or device failure. Thus, protein- and platelet-resistant blood-contacting interfaces on devices as mentioned above can improve patient outcomes and reduce the overall cost of care. A first-generation synthetic vascular graft is the subject of our investigation. The polymer compositions in these studies are sulfonated block copolymer blends that have demonstrated low thrombogenicity, good (wet) mechanical properties, and can be electrospun into 3-D vascular graft constructs. Dynamic studies of the electrospun graft (under flow) will be used to understand the materials behavior in blood.