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: 10221033
• 负责人: DANNY BLUESTEIN
• 金额: $ 67.56万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221033
• 关键词: Acute; Adverse event; Animals; Aortic Valve Stenosis; Benchmarking; Biological Assay; Biological Markers; Bioprosthesis device; Blood Platelets; Blood Vessels; Businesses; Cardiac; Cardiovascular system; Catheters; Chronic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complication; Corrosion; Coupled; Cyclic GMP; Deposition; Deterioration; Development; Devices; Dimensions; Distal; Embolism; Euthanasia; Event; Extravasation; Failure; Follow-Up Studies; Freezing; Future; Generations; Geometry; Goals; Grant; Guidelines; Heart; Heart Valves; Hemolysis; Histologic; Implant; In Situ; In Vitro; Institution; Left; Life; Life Cycle Stages; Longterm Follow-up; Manufacturer Name; Measures; Medical Device; Methodology; Microscopic; Molds; Molecular Conformation; Monitor; National Institute of Biomedical Imaging and Bioengineering; Operative Surgical Procedures; Organ; Outcome; Pathology; Patients; Performance; Phase; Plant Roots; Polymers; Population; Principal Investigator; Procedures; Process; Prosthesis; Radial; Regulation; Resistance; Risk; Risk Factors; Safety; Savings; Serious Adverse Event; Sheep; Small Business Technology Transfer Research; Standardization; Stents; Stress; Stroke; Surface; Surgical Valves; System; Technology; Testing; Therapeutic Embolization; Thick; Thrombosis; Tissues; Translating; United States National Institutes of Health; Universities; Ventricular; Work; X-Ray Computed Tomography; aortic valve; aortic valve disorder; aortic valve replacement; base; biomaterial compatibility; bone; calcification; commercialization; crosslink; cytotoxicity; design; effective therapy; efficacy testing; experimental study; first-in-human; genotoxicity; heart imaging; hemocompatibility; hemodynamics; high risk; improved; in vitro testing; in vivo; in vivo evaluation; innovation; manufacturing process; mechanical properties; meetings; migration; minimally invasive; new technology; novel; older patient; oxidation; patient population; performance tests; pre-clinical; pressure; programs; prototype; quantum; replicator; research and development; sheep model; simulation; success; thrombogenesis; thrombotic; 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. In a collaboration between Stony Brook University and PolyNova Cardiovascular, Inc., we have 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 hemodynamics, 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. Following a successful Phase I STTR project, in this Phase II project we aim to expand the R&D activities of our polymeric valve toward First-In-Man, and implement a robust regulatory and quality management system plans. The proposed project includes 4 Aims: Aim 1 expand our set of advanced computational flow simulations, development of a 2nd generation valve, development of a dedicated delivery catheter system, and expanding our valve product to a complete set of valve sizes. Aim 2 tests the valve performance according to the ISO 5840-3 (transcatheter heart valves), ISO 25539-1 (cardiovascular implants), and ISO10993-1 (biocompatibility). We will also modify our valve manufacturing capabilities to be compliant with the FDA quality management system. Aim 3 tests the valves in vivo in sheep model. The valves are tested for efficacy and safety in acute tests as well as chronic 10 and 20 wks. Aim 4 is dedicated for integrating regulatory and business plans for PolyNova and for the valve technology. Integral to this STTR Phase II project is a detailed commercialization and regulatory plan, based on which, and under the support of this Phase II program, we will convert PolyNova from a pure R&D shop to firm establishment as a qualified medical device manufacturer– i.e. institution of a fully cGMP, FDA compliant Quality Management System including a robust Design Control process. 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.

项目摘要：用于经导管主动脉瓣置换术的新型聚合物瓣膜 微创经导管主动脉瓣置换术 (TAVR) 已成为治疗未满足治疗需求的有效疗法 无法手术的严重主动脉瓣狭窄（AS）患者的临床需求。最近 TAVR 的纵向随访研究 然而，患者表示该手术和相关技术可能会导致严重的不良事件。当前的 技术基于适应 TAVR 的组织瓣膜，但并非专门为 TAVR 设计。这些可能会受到损害 在压接和展开过程中，容易发生“骨状”钙化沉积，并且受到有限的影响 耐用性。在石溪大学和 PolyNova Cardioangio, Inc. 的合作中，我们开发了 一种新型阀门，专为解决 TAVR 瓣膜在使用过程中遇到的众多挑战而设计 生命周期，从压接到部署以及现场长期性能。它结合了（i）新颖的聚合物技术， xSIBS，结合了卓越的生物稳定性和优异的机械性能，以及 (ii) 新颖的设计 用于增强血流动力学、耐用性和抗血栓性的传单轮廓的优化方法 表现。 我们的总体目标是开发一种可行且耐用的 TAVR 瓣膜，为现有的 TAVR 瓣膜提供真正的替代品 生物主动脉瓣膜，并提供适合更广泛人群的长期解决方案。下列的 作为一个成功的第一阶段 STTR 项目，在这个第二阶段项目中，我们的目标是扩大我们的聚合物阀门的研发活动 迈向“First-In-Man”，并实施强有力的监管和质量管理体系计划。 拟议项目包括 4 个目标：目标 1 扩展我们的高级计算流模拟集， 开发第二代瓣膜、开发专用输送导管系统并扩展我们的瓣膜 产品到一整套阀门尺寸。目标 2 根据 ISO 5840-3（经导管 心脏瓣膜）、ISO 25539-1（心血管植入物）和 ISO10993-1（生物相容性）。我们还将修改我们的 阀门制造能力符合 FDA 质量管理体系。目标 3 测试阀门 绵羊模型体内。这些阀门在急性测试以及 10 周和 20 周的慢性测试中进行了有效性和安全性测试。 Aim 4 致力于整合 PolyNova 和阀门技术的监管和业务计划。 STTR 第二阶段项目的组成部分是详细的商业化和监管计划，并在此基础上制定 在这个二期项目的支持下，我们将把PolyNova从一个纯粹的研发机构转变为一家公司 合格的医疗器械制造商——即建立完全符合 cGMP、FDA 要求的质量管理体系 包括强大的设计控制流程。 上述目标的成功实现将为主动脉瓣疾病的治疗带来突破， 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。