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

基本信息

批准号：
10464978
负责人：
DANNY BLUESTEIN
金额：
$ 59.43万
依托单位：
POLYNOVA CARDIOVASCULAR, INC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10464978
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

项目摘要

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。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。技术基于适合 TAVR 的组织瓣膜，但不是专门为那些可能遭受损伤的组织瓣膜设计的。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我们与石溪大学和 PolyNova Cardioangio, Inc. 合作开发了耐用性。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采用了 (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，并为更广泛的人群提供长期解决方案。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 Aim 2 根据 ISO 5840-3（经导管）测试阀门性能。我们还将修改我们的标准（心脏瓣膜）、ISO 25539-1（心血管植入物）和 ISO10993-1（生物相容性）。阀门制造能力符合 FDA 质量管理体系 Aim 3 测试阀门。在绵羊模型体内测试了瓣膜的有效性和安全性，包括急性测试以及慢性 10 周和 20 周。 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，并以此为基础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——即拥有完全符合 cGMP、FDA 要求的质量管理体系的机构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。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mild Paravalvular Leak May Pose an Increased Thrombogenic Risk in Transcatheter Aortic Valve Replacement (TAVR) Patients-Insights from Patient Specific In Vitro and In Silico Studies.

轻度瓣周漏可能会增加经导管主动脉瓣置换术 (TAVR) 患者的血栓形成风险 - 来自患者特定体外和计算机研究的见解。

DOI：
发表时间：
2023-02-01
期刊：
影响因子：
0
作者：
Kovarovic, Brandon J;Rotman, Oren M;Parikh, Puja B;Slepian, Marvin J;Bluestein, Danny
通讯作者：
Bluestein, Danny

Patient-specific in vitro testing for evaluating TAVR clinical performance-A complementary approach to current ISO standard testing.

用于评估 TAVR 临床表现的患者特异性体外测试 - 现行 ISO 标准测试的补充方法。

DOI：
发表时间：
2021-04
期刊：
影响因子：
2.4
作者：
Kovarovic, Brandon J;Rotman, Oren M;Parikh, Puja;Slepian, Marvin J;Bluestein, Danny
通讯作者：
Bluestein, Danny

Visions of TAVR Future: Development and Optimization of a Second Generation Novel Polymeric TAVR.

TAVR 未来的愿景：第二代新型聚合物 TAVR 的开发和优化。

DOI：
发表时间：
2022-06-01
期刊：
影响因子：
0
作者：
Kovarovic, Brandon;Helbock, Ryan;Baylous, Kyle;Rotman, Oren M;Slepian, Marvin J;Bluestein, Danny
通讯作者：
Bluestein, Danny