A Novel Thin Film Nitinol Covered Stent to Treat Peripheral Arterial Disease

描述（由申请人提供）：本申请涉及广泛的挑战领域（15）转化研究和特定的挑战主题，15-HL-101：为植入式血液接触医疗器械开发改进的生物相容性表面。外周动脉疾病（PAD）发生在3-10%的普通人群中，在70岁以上的人群中增加到10-15%。由于缺乏合适的生物相容性表面来覆盖这些导致血栓形成的血液接触器械，PAD血管内治疗的进展受到限制。血管内器械的适当抗血栓材料的可用性可显著改善PAD的总体死亡率和发病率。加州大学洛杉矶分校开发了一种独特的工艺，可以生产超亲水性和抗血栓的薄膜镍钛诺。我们的假设是，这种材料将非常适合治疗PAD，而不会出现通常与当前血管内治疗相关的并发症。我们计划设计、制造和测试一种用于治疗PAD的超亲水涂层薄膜镍钛合金（S-TFN）覆膜支架。大量镍钛诺存在于许多医疗器械中，包括最显著的支架。尽管由于钛氧化物层而具有惰性，但由于大块镍钛诺的表面粗糙度和钛氧化物层的整体质量而发生血栓形成。我们的实验室已经开发出一种新颖的专利方法，利用溅射沉积技术制造薄膜镍钛诺（TFN）。与大块镍钛合金相比，表面粗糙度平滑两个数量级，与传统方法相比，成分变化小于四倍。一种新型的表面处理（专利申请中）也已开发出来，以创造一个超亲水层，排斥带负电荷的血液制品，防止血栓形成。这种表面抵抗血栓形成的功效已经通过最近的体内和体外试验得到证实。与市售支架覆膜（如聚四氟乙烯（PTFE））相比，S-TFN上的血小板粘附显著降低。短期初步猪体内研究也证明，S-TFN覆膜支架支持内皮生长，无不必要的新生内膜增生或血栓形成。该提案基于UCLA已经对S-TFN进行的研究，以分析、制造和全面测试用于治疗PAD的S-TFN覆膜支架。本提案的三个主要组成部分是：1）根据ISO标准评价S-TFN覆膜支架的生物相容性标准，用于留置医疗器械; 2）分析、设计、制造和试验专门用于治疗PAD的S-TFN覆膜支架; 3）最终研究短、中、在猪模型的外周血管系统中长期放置S-TFN覆膜支架，并将结果与传统PTFE覆膜支架进行比较。四肢动脉闭塞性疾病发生在3-10%的人群中，在70岁以上的人群中增加到10-15%。用于治疗这种闭塞性疾病的医疗器械的最大障碍是血栓形成，血栓形成是在植入器械内形成的血块。为了解决这个问题，加州大学洛杉矶分校已经开发了一种新的表面处理薄膜镍钛诺，在初步研究中，防止血栓形成，因此非常适合治疗肢体闭塞性疾病。 公共卫生相关性：四肢动脉闭塞性疾病发生在3-10%的人群中，在70岁以上的人群中增加到10-15%。用于治疗这种闭塞性疾病的医疗器械的最大障碍是血栓形成，即在植入的器械内形成血块。为了解决这个问题，加州大学洛杉矶分校已经开发了一种新的表面处理薄膜镍钛诺，在初步研究中，防止血栓形成，因此非常适合治疗肢体闭塞性疾病。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (15) Translational Research and specific Challenge Topic, 15-HL-101: Develop Improved Biocompatible Surfaces for Implantable Blood-Contacting Medical Devices. Peripheral arterial disease (PAD) occurs in 3-10% of the general population and increases to 10-15% in persons over 70 years. Advancements in endovascular therapies for PAD are limited by the lack of a suitable, biocompatible surface for the covering of these blood-contacting devices that lead to thrombosis. The availability of an appropriate, thrombus resistant material for endovascular devices could lead to significant improvements in the over-all mortality and morbidity of PAD. UCLA has developed a unique process that can produce super-hydrophilic and thrombus-resistant thin film Nitinol. It is our hypothesis that this material will be ideally suited for treating PAD without the complications normally associated with current endovascular treatments. We propose to design, fabricate and test a super hydrophilic coated thin film Nitinol (S-TFN) covered stent both in vivo and in vitro for the treatment of PAD. Bulk Nitinol is found in many medical devices including most notably stents. Despite being inert due to its titanium oxide layer, thrombosis occurs due to bulk Nitinol's surface roughness and the overall quality of the titanium oxide layer. Our laboratory has developed a novel patented means to fabricate thin film Nitinol (TFN) using a sputter deposition technique. Surface roughness is two orders of magnitudes smoother when compared to bulk Nitinol and compositional variations less than four times compared to conventional approaches. A novel surface treatment (patent pending) has also been developed to create a super hydrophilic layer which repels negatively charged blood products and prevents thrombosis. The efficacy of this surface to resist thrombosis has been confirmed with recent in vivo and in vitro tests. Platelet adhesion on the S-TFN is significantly reduced compared to commercially available stent coverings such as polytetrafluoroethylene (PTFE). Short term preliminary in vivo swine studies have also demonstrated that S-TFN covered stents support endothelial growth without unwanted neointimal hyperplasia or thrombosis. This proposal builds upon the research already conducted at UCLA on S-TFN to analyze, fabricate, and thoroughly test S-TFN covered stents for treating PAD. The three major components of this proposal are 1) to evaluate S-TFN covered stents for biocompatibility criteria under the ISO standards for indwelling medical devices 2) analyze, design, fabricate, and test a S-TFN covered stent specifically for treating PAD and 3) to finally investigate short, medium, and long term placement of S-TFN covered stents in the peripheral vasculature of a swine model and compare the results to conventional PTFE covered stents. Arterial occlusive disease of the extremities occurs in 3-10% of the population and increases to 10-15% in persons over 70 years. The biggest hurdle for medical devices used in the treatment of this occlusive disease is thrombosis, which is blood clots developing within the implanted device. To solve this problem, UCLA has developed a new surface treatment for thin film Nitinol that in preliminary studies prevents thrombosis and thus is ideally suited for treating occlusive disease of the extremities. PUBLIC HEALTH RELEVANCE: Arterial occlusive disease of the extremities occurs in 3-10% of the population and increases to 10-15% in persons over 70 years. The biggest hurdle for medical devices used in the treatment of this occlusive disease is thrombosis, that is blood clots develop within the implanted device. To solve this problem, UCLA has developed a new surface treatment for thin film Nitinol that in preliminary studies prevents thrombosis and thus is ideally suited for treating occlusive disease of the extremities.