A Novel Thin Film Nitinol Covered Carotid Artery Embolic Protection Stent

描述（由申请人提供）：卒中和动脉粥样硬化性脑血管疾病发生在全球约9%的人群中，近75%的卒中发生在65岁以上的人群中。约30%的脑卒中患者归因于动脉粥样硬化性颈动脉狭窄。虽然目前用于颈动脉狭窄的血管内治疗显示出可行性和安全性，但它们需要多个步骤，例如球囊血管成形术和使用单独的栓塞保护滤器装置放置支架。因此，迫切需要开发简单、安全和有效的血管内技术来治疗颈动脉狭窄，而无需额外放置过滤器装置（即，栓塞保护“过滤器”装置）。一个例子是覆盖有超薄微图案化膜（即，覆膜支架移植物）。用于颈动脉狭窄的支架移植物技术的进步受到缺乏用于栓塞保护支架的覆盖的合适的生物相容性材料的限制。血管内器械的适当抗血栓材料的可用性可显著改善颈动脉狭窄引起的卒中的总体死亡率和发病率。匹兹堡大学开发了一种新型微图案化薄膜镍钛合金（TFN）覆膜支架。我们还开发了一种独特的工艺，可以生产超亲水和抗血栓的TFN。我们假设，这种含有微图案化TFN膜的新开发器械可以生产超低切迹的覆膜支架，并降低颈动脉支架植入术期间/之后的栓塞风险。此外，这种材料独特的表面质量将在颈动脉狭窄的治疗中显著减少支架血栓形成和新生内膜生长。该提案概述了一种新型薄膜镍钛合金覆膜颈动脉栓塞保护支架的研发计划，该支架具有非血栓形成性和超低切迹，能够持续预防术中/术后远端栓塞。讨论了与当前颈动脉狭窄治疗手术相关的问题和并发症，以及低切迹、非血栓形成、微图案TFN覆膜支架的需求和有用性。提出了一项基本的体外静态生物相容性研究，以证明带负电荷的超亲水性TFN表面在细胞毒性、细胞生长行为和抗血栓性方面具有上级优势。将用结构建模工具（即，有限元解和计算机辅助设计软件）。随后，提出了一个两阶段的制造方案（将在匹兹堡大学纳米/微制造设施和生物制造血管装置实验室进行）。设计的第一阶段将微图案化TFN与市售裸金属支架结合。设计的第二阶段将整个装置折叠成输送导管（例如，5.0 Fr），显示了器械与现有输送导管的兼容性和兼容性。提出了一种用于在微流体装置中使用人工栓子和可生物降解聚合物涂层的装置的功效的新型体外装置，以显示装置设计如何提供TFN移植膜中微孔的最佳尺寸和几何形状。提出了体外装置来定量测量分离的微粒（即，人工栓塞）与各种微图案化的TFN移植膜。

DESCRIPTION (provided by applicant): Stroke and atherosclerotic cerebrovascular disease occurs in approximately 9% of the population worldwide and nearly 75% of all strokes occur in persons over 65 years. Approximately 30% of the stroke patients have been attributed to atherosclerotic carotid artery stenosis. While current endovascular therapies for carotid artery stenosis show feasibility and safety, they require multiple steps such as balloon angioplasty and placement of stents with the separate embolic protection filter devices. Therefore, a critical need exists for developing endovascular technology to treat carotid artery stenosis that is simple, safe and effective without additional placement of filter devices (i.e., emboli-protection "filter" device) during the procedure. One example would be an embolic protection stent covered with ultra-thin micro-patterned membrane (i.e., covered stent graft) on bare metal stents. Advancements in stent graft technologies for carotid artery stenosis are limited by the lack of a suitable, biocompatible material for the covering of the embolic protection stent. The availability of an appropriate, thrombus resistant material for endovascular devices could lead to significant improvements in the overall mortality and morbidity of strokes induced by carotid artery stenosis. The University of Pittsburgh has developed a novel micro-patterned thin film nitinol (TFN) covered stent. We have also developed a unique process that can produce superhydrophilic and thrombus resistant TFN. It is our hypothesis that this newly developed device containing the micro-patterned TFN membrane can produce endografts which is ultra-low profile and decrease the risk of embolization during/after carotid artery stenting. In additio, the unique surface qualities of this material will provide a substantial reduction in stent thrombosis and neointima growth in the treatment of carotid artery stenosis. This proposal outlines a plan for research and development of a novel thin film nitinol covered carotid artery embolic protection stent that is non-thrombogenic and ultra-low profile, as well as capable of continuously preventing intra-/post-operative distal embolization. Problems and complications associated with current carotid artery stenosis treatment procedures, as well as the need and usefulness of low profile, non- thrombogenic, micro-patterned TFN covered stents are discussed. A fundamental in vitro static biocompatibility studies are proposed to demonstrate superior in cytotoxicity, cell growth behavior, and thromboresistance of the negatively-charged superhydrophilic TFN surface. A novel design which prevents the dislodgement of thrombosis or cholesterol from the vascular wall will be studied with structural modeling tools (i.e., finite element solution and computer aided design software). Subsequently, a two-stage fabrication scheme (to be carried out at University of Pittsburgh Nano/Microfabrication facilities and Biomanufacturing-Vascular Device Laboratory) is proposed. The first stage of the design incorporates a micro-patterned TFN with a commercially available bare metal stent. The second stage of the design collapses the whole device into delivery catheters (e.g.,5.0Fr), showing collapsibility and compatibility of the device with existing delivery catheters. A novel i vitro apparatus for the efficacy of the device using an artificial emboli and biodegradable polymer coating in microfluidic devices is presented in order to show how the device design provides optimal dimension and geometry of micro pores in TFN graft membrane. The in vitro apparatus is proposed to quantitatively measure the detached micro particles (i.e., artificial emboli) with the various micro-patterned TFN graft membrane.