A Novel Electrospun Vascular Graft

新型静电纺血管移植物

• 批准号: 7805685
• 负责人: DAVID J VACHON
• 金额: $ 27.78万
• 依托单位: IASIS MOLECULAR SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7805685
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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.

描述（由申请人提供）：具有独特的化学可定制性质和加工特性的新型磺化聚合物已经显示出作为抗血栓表面的相当大的前景，并且已经被证明是针对嗜中性粒细胞衍生的蛋白酶的有效抑制剂。建议进行第1阶段SBIR试验，以研究该聚合物作为血管移植材料的混合物。所提出的研究的主要具体目标涉及使用静电纺丝技术从这些材料制造第一代血管移植物，并研究移植物在血液流动下的性能。主要目的是尽量减少血小板粘附和活化。这种创新和合理的抗血栓血液管道的方法是建立在几个不同的研究的基础上，这些研究揭示了这种聚合物家族有前途的生物适用性属性。该第一阶段SBIR的最终目标是开发和确定一种固有的非血栓形成和抗炎水凝胶（混合物）表面，其可能用作血管移植物和其他救生心血管装置。 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，目前影响了超过7000万美国人。总体而言，每年有600多万人因心血管疾病住院治疗。因此，CVD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年心脏病和中风的费用（美国）超过4000亿美元，其中包括医疗保健成本支出和死亡和残疾造成的生产力损失。 在心血管疾病的保护伞下，动脉粥样硬化诱导的外周动脉疾病（PAD）、冠状动脉疾病（CAD）和脑血管疾病都是由血管狭窄（狭窄）和/或闭塞的原发性事件引起的，所述血管狭窄和/或闭塞是由于凝块的失调形成以及涉及平滑肌细胞（SMC）浸润、新生内膜增殖和适应不良的血管重塑的相关炎症事件。狭窄和闭塞导致顺行血流减少/丧失。对于PAD，这可能导致跛行和外周肢体的组织发病，而对于CAD，这可能导致缺血和通常致命的心肌梗死，对于脑血管情况，这可能导致中风。介入性血管内和/或手术治疗以清除血栓并重建血管血流是这些疾病的临床管理所必需的。血管内治疗涉及机械方法，如导管介导的血管成形术、冷冻成形术和内膜切除术，以及药物治疗方法，如经导管递送溶栓、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。近年来已经看到药物洗脱支架（DES）的发展，其中金属支架表面涂覆有用于持续释放治疗剂的载药聚合物基质。手术方法涉及旁路移植物，其中许多由合成聚合物（例如ePTFE）制成。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。所有上述装置都依赖于与流动的血液接触的合成材料。这些材料易于发生快速蛋白质（例如纤维蛋白原、纤维蛋白）沉积、变性和随后的血小板粘附和活化，可能导致凝块形成和随后的凝血活化和炎症事件。反过来，材料性能可能会受到影响，需要重复血管内或外科手术。因此，这些患者通常需要永久抗凝治疗，以防止卒中和/或器械失效。因此，如上所述的装置上的抗蛋白质和抗血小板的血液接触界面可以改善患者结果并降低护理的总成本。 第一代人造血管移植物是我们研究的主题。这些研究中的聚合物组合物是磺化嵌段共聚物共混物，其已证明具有低促凝性、良好的（湿）机械性能，并且可以静电纺丝成3-D血管移植物构造。电纺移植物的动态研究（在流动下）将用于了解材料在血液中的行为。