A Novel Thin Film Nitinol Covered Carotid Artery Embolic Protection Stent

新型薄膜镍钛合金覆盖颈动脉栓塞保护支架

• 批准号: 8771754
• 负责人: Young Jae Chun
• 金额: $ 7.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8771754
• 关键词: Area; Arteries; Balloon Angioplasty; Behavior; Biocompatible Materials; Biological Assay; Biomanufacturing; Blood; Blood Vessels; Blood coagulation; Caliber; Carotid Arteries; Carotid Artery Diseases; Carotid Stenosis; Catheters; Cell Adhesion; Cerebrovascular Circulation; Cerebrovascular Disorders; Charge; Cholesterol; Computer software; Computer-Aided Design; Coupled; Data; Development; Device Designs; Devices; Dimensions; Disease; Distal; Elements; Embolism; Endothelial Cells; Fatigue; Film; Finite Element Analysis; Geometry; Goals; Growth; Health; Human Resources; Hyperplasia; In Vitro; Incidence; Incubators; Ischemic Stroke; Knowledge; Laboratories; Lead; Life; Location; Measures; Medical Device; Membrane; Metals; Microfabrication; Microfluidic Microchips; Microfluidics; Microscope; Modeling; Morbidity - disease rate; Patients; Pattern; Persons; Polymers; Population; Postoperative Period; Prevention; Problem Solving; Procedures; Process; Research Personnel; Resistance; Risk; Safety; Scheme; Smooth Muscle Myocytes; Solutions; Staging; Stents; Stream; Stroke; Stroke prevention; Structural Models; Supporting Cell; Surface; System; Techniques; Technology; Testing; Therapeutic Embolization; Thrombosis; Thrombus; Time; Transplanted tissue; Universities; Vascular Diseases; Video Microscopy; Work; biodegradable polymer; biomaterial compatibility; cell growth; cell motility; charge coupled device camera; cytotoxicity; design; in vitro testing; in vivo; innovation; meetings; mortality; nano; nitinol; novel; particle; poly(lactic acid); prevent; prototype; research and development; tool; Area; Arteries; Balloon Angioplasty; Behavior; Biocompatible Materials; Biological Assay; Biomanufacturing; Blood; Blood Vessels; Blood coagulation; Caliber; Carotid Arteries; Carotid Artery Diseases; Carotid Stenosis; Catheters; Cell Adhesion; Cerebrovascular Circulation; Cerebrovascular Disorders; Charge; Cholesterol; Computer software; Computer-Aided Design; Coupled; Data; Development; Device Designs; Devices; Dimensions; Disease; Distal; Elements; Embolism; Endothelial Cells; Fatigue; Film; Finite Element Analysis; Geometry; Goals; Growth; Health; Human Resources; Hyperplasia; In Vitro; Incidence; Incubators; Ischemic Stroke; Knowledge; Laboratories; Lead; Life; Location; Measures; Medical Device; Membrane; Metals; Microfabrication; Microfluidic Microchips; Microfluidics; Microscope; Modeling; Morbidity - disease rate; Patients; Pattern; Persons; Polymers; Population; Postoperative Period; Prevention; Problem Solving; Procedures; Process; Research Personnel; Resistance; Risk; Safety; Scheme; Smooth Muscle Myocytes; Solutions; Staging; Stents; Stream; Stroke; Stroke prevention; Structural Models; Supporting Cell; Surface; System; Techniques; Technology; Testing; Therapeutic Embolization; Thrombosis; Thrombus; Time; Transplanted tissue; Universities; Vascular Diseases; Video Microscopy; Work; biodegradable polymer; biomaterial compatibility; cell growth; cell motility; charge coupled device camera; cytotoxicity; design; in vitro testing; in vivo; innovation; meetings; mortality; nano; nitinol; novel; particle; poly(lactic acid); prevent; prototype; research and development; tool

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.

描述（由申请人提供）：中风和动脉粥样硬化脑血管疾病发生在全球大约9％的人口中，近75％的中风发生在65年以上。大约30％的中风患者归因于动脉粥样硬化颈动脉狭窄。虽然目前用于颈动脉狭窄的血管内疗法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带有单独的栓塞保护滤器装置的支架。因此，存在着开发血管内技术来治疗颈动脉狭窄的关键需求，该动脉狭窄在过程中简单，安全且有效，而没有额外的滤清器设备（即，在过程中，Emboli-Totection“过滤器”设备）。一个例子是一个栓塞支架，上面覆盖着超薄的微图案膜（即覆盖的支架移植物）裸露的金属支架。颈动脉狭窄的支架移植技术的进步受到缺乏合适的生物相容性材料来覆盖栓塞保护支架的限制。适当的，抗血栓的材料可用于血管内装置，可能会导致颈动脉狭窄引起的中风的总死亡率和发病率显着改善。匹兹堡大学开发了一种新型的微图案薄膜尼丁醇（TFN）覆盖的支架。我们还开发了一个独特的过程，可以产生抗嗜水和抗血栓的TFN。我们的假设是，这种包含微图案TFN膜的新开发的装置可以产生内ro移植，这是超低轮廓，并降低了颈动脉支架置换期间/之后的栓塞风险。从而增加，该材料的独特表面质量将大大降低支架血栓形成和颈动脉狭窄治疗的新内膜生长。该建议概述了一种新型薄膜奈蒂诺覆盖的颈动脉栓塞保护支架的研究和开发计划，该支架具有非紧张性和超低特征，并且能够连续防止术中/后术中远端远端栓塞。讨论了与当前颈动脉狭窄治疗程序以及低调，非血小板，微观图案TFN覆盖支架的需求和有用性有关的问题和并发症。提出了一项基本的体外静态生物相容性研究，以证明否定性超养分TFN表面的细胞毒性，细胞生长行为和动脉筋。将使用结构建模工具（即有限元解决方案和计算机辅助设计软件）研究了一种新型设计，该设计可防止血栓形成或胆固醇从血管壁中移出。随后，提出了一个两阶段的制造计划（在匹兹堡纳米/微加工设施和生物制造 - 血管装置实验室进行）。设计的第一阶段结合了一个微图案的TFN，并带有商业上可用的裸金属支架。设计的第二阶段使整个设备倒入输送导管（例如5.0FR），显示了该设备与现有输送导管的兼容性。为了展示该设备设计如何提供TFN Graft Membrane中微孔的最佳尺寸和微孔的几何形状，提出了使用人工栓子和可生物降解的聚合物涂层在设备上的功效的新型I体外设备。提出了体外设备，以定量测量具有各种微图案TFN移植膜的分离的微粒（即人造栓子）。