A Novel Polymeric Valve for Transcatheter Aortic Valve Replacement

用于经导管主动脉瓣置换的新型聚合物瓣膜

• 批准号: 9344868
• 负责人: DANNY BLUESTEIN
• 金额: $ 11.47万
• 依托单位: POLYNOVA CARDIOVASCULAR, INC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9344868
• 关键词: 3D Print; Adverse event; Anatomy; Animals; Aortic Valve Stenosis; Berlin; Biological Assay; Bioprosthesis device; Blood; Blood Platelets; Blood Vessels; Calcified; Cardiovascular system; Chronic; Clinical; Clinical Research; Collaborations; Complication; Computer Simulation; Cyclic GMP; Deposition; Deterioration; Devices; Dissection; Evaluation; Extravasation; Follow-Up Studies; Generations; Geometry; Goals; Grant; Heart; Heart Valve Prosthesis; In Situ; In Vitro; Left; Licensing; Life; Life Cycle Stages; Liquid substance; Measures; Methodology; Modeling; Molds; National Institute of Biomedical Imaging and Bioengineering; Operative Surgical Procedures; Outcome; Pathway interactions; Patient risk; Patients; Performance; Phase; Physiological; Plant Roots; Platelet Activation; Polymers; Population; Predisposition; Preparation; Procedures; Process; Prosthesis; Protocols documentation; Publishing; Risk; Risk Factors; Rupture; Savings; Serious Adverse Event; Silicones; Small Business Technology Transfer Research; Stents; Stress; Stroke; Structure; Surgical Valves; System; Technology; Testing; Therapeutic Embolization; Thick; Thrombosis; Tissues; Translating; United States National Institutes of Health; Universities; X-Ray Computed Tomography; aortic valve; aortic valve disorder; aortic valve replacement; base; bone; calcification; commercialization; crosslink; design; effective therapy; experimental study; follow-up; hemodynamics; high risk; improved; in vivo; innovation; left ventricular assist device; mechanical properties; migration; minimally invasive; new technology; novel; older patient; patient population; pressure; programs; prototype; quantum; replicator; research and development; simulation; success; valve replacement; verification and validation

Project Summary: A Novel Polymeric Valve for Transcatheter Aortic Valve Replacement Minimally invasive transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for the unmet clinical need of inoperable patients with severe aortic stenosis (AS). Recent longitudinal follow-up studies of TAVR patients however indicate that this procedure and associated technology may result in serious adverse events. Current technology is based on tissue valves adapted to, but not specifically designed for TAVR. Those may sustain damage during crimping as well as deployment, are susceptible to ‘bone-like’ calcific deposition, and suffer from limited durability. Our group has developed a novel valve that is specifically designed to tackle the numerous challenges that a TAVR valve will meet during its life cycle, from crimping to deployment and long term performance in situ. It incorporates (i) novel polymer technology, xSIBS, which combines superior bio-stability together with excellent mechanical properties, and (ii) a novel design optimization methodology of the leaflets profile for enhanced hemodynamic, durability, and thromboresistance performance. Our broad objective is to develop a viable and durable TAVR valve that will propose a real alternative to existing bioprosthetic aortic valves, and allow a long-term solution adequate for broader segment of the population. This Phase I STTR project, in a collaboration between Stony Brook University and PolyNova Cardiovascular Inc, aims to shift our existing novel polymeric prosthetic heart valve to a TAVR application, providing proof-of-concept. This will be tested in four aims: Aim 1 analyses the hydrodynamic performance in silico both in standard as well as in patient- specific anatomy, quantify its thrombogenic potential, and compares it to a commercially available valve. Aim 2 tests the hydrodynamic performance in vitro, using standard and patient-specific anatomy, and evaluates damage to the polymer as a result of valve crimping. Aim 3 quantifies the thromboresistance profile of the valve via platelet activation under physiological flow conditions. Aim 4 evaluates the durability performance and calcification susceptibility under accelerated wear testing conditions. Successful accomplishment of the above aims will lead to a breakthrough in the treatment of aortic valve diseases, providing an affordable, long-term, minimally invasive solution, enhancing the life of a much broader patient population.

项目总结：一种用于经导管主动脉瓣置换的新型聚合物瓣膜 微创经导管主动脉瓣置换术(TAVR)已成为治疗高血压病的一种有效方法。 不能手术的严重主动脉狭窄患者的临床需求未得到满足。最近的纵向随访研究 然而，TAVR患者表示，这种程序和相关技术可能会导致严重的不良反应 事件。目前的技术是基于适应于TAVR的组织瓣，但不是专门为TAVR设计的。那些可能 在卷曲和展开过程中受到损害，容易发生骨样钙化沉积，并遭受 从有限的耐用性。我们团队已经开发出一种新的阀门，这种阀门是专门为应对无数 TAVR阀门在其生命周期中将遇到的挑战，从卷曲到部署和长期性能 在原地。它结合了(I)新的聚合物技术xSIBS，它结合了卓越的生物稳定性和 优异的机械性能，以及(Ii)一种新的叶型设计优化方法，用于增强 血液动力学、耐用性和抗血栓性能。 我们的广泛目标是开发一种可行和耐用的TAVR瓣膜，它将提出一种真正的替代现有的TAVR瓣膜 生物瓣膜，并允许一个长期的解决方案，足以满足更广泛的人群。这 第一阶段STTR项目由石溪大学和PolyNova心血管公司合作，旨在 将我们现有的新型聚合物人工心脏瓣膜应用于TAVR，提供概念验证。这将是 在四个目标下进行测试：目标1在标准和患者中分析硅橡胶的水动力性能。 具体解剖，量化其血栓形成潜力，并将其与商业上可用的瓣膜进行比较。AIM 2测试 体外流体动力学性能，使用标准和患者特定的解剖结构，并评估对 由于阀门卷曲而产生的聚合物。AIM 3通过血小板量化瓣膜的血栓抵抗特性 生理流动条件下的激活。目的4评估耐久性能和钙化 在加速磨损试验条件下的敏感性。 上述目标的成功实现将使主动脉瓣疾病的治疗取得突破， 提供负担得起的、长期的、微创的解决方案，改善更广泛患者的生活 人口。