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: 9903032
• 负责人: DANNY BLUESTEIN
• 金额: $ 71.92万
• 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/9903032
• 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; Modeling; 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; simulation; success; thrombogenesis; 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：经导管主动脉瓣更换的新型聚合物阀 最低侵入性的经导管主动脉瓣置换（TAVR）已成为一种未经满足的有效疗法 严重主动脉瓣狭窄的无法手术患者（AS）的临床需求。 TAVR的最新纵向随访研究 但是，患者表明该程序和相关技术可能会导致严重的不良事件。当前的 技术基于适合TAVR的组织阀，但不是专门设计的。这些可能会造成损害 在压接和部署期间，容易受到“骨状”钙化沉积的影响，并且患有有限的 耐用性。在Stony Brook University与Polynova Cardiescular，Inc。之间的合作中，我们已经开发了 一个专门设计的新型阀门，以应对TAVR阀在其期间面临的众多挑战 生命周期，从犯下部署到部署，以及原位的长期表现。它结合了（i）新型聚合物技术， XSIBS，将卓越的生物稳定性与出色的机械性能结合在一起，以及（ii）新型设计 传单的优化方法，用于增强血液动力学，耐用性和血栓的方法 表现。 我们广泛的目标是开发一个可行耐用的TAVR阀，该阀将提出真正的替代品 生物假体主动脉瓣，并允许长期解决方案足以适应更广泛的人群。下列的 成功的I阶段STTR项目，在此阶段II阶段项目中，我们旨在扩大聚合物阀的研发活动 迈向第一名，并实施强大的监管和质量管理系统计划。 拟议的项目包括4个目标：AIM 1扩展我们的高级计算流仿真集， 开发第二代阀，专用输送导管系统的开发以及扩展我们的阀门 产品达到完整的阀尺寸。 AIM 2根据ISO 5840-3（经导管）测试阀的性能 心脏瓣膜），ISO 25539-1（心血管叉）和ISO10993-1（生物相容性）。我们还将修改我们的 阀制造功能符合FDA质量管理系统。 AIM 3测试阀中的阀门 绵羊模型的体内。在急性测试以及慢性10和20周中，对阀门进行了效率和安全性测试。 AIM 4致力于整合多克萨娃和阀门技术的监管和业务计划。 该STTR II阶段项目不可或缺的是一个详细的商业化和监管计划，该计划基于该计划 在此II阶段计划的支持下，我们将将Polynova从纯研发商店转换为公司机构 合格的医疗设备制造商 - 即完全CGMP的机构，符合FDA的质量管理系统 包括强大的设计控制过程。 成功完成上述目标将导致主动脉瓣疾病治疗的突破， 提供负担得起的长期，微创的解决方案，增强了更广泛的患者的寿命 人口。