A Novel Polymeric Valve for Transcatheter Aortic Valve Replacement

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)已成为治疗非MET的有效方法。 不能手术的重度主动脉狭窄(AS)患者的临床需求。TAVR的最新纵向随访研究 然而，患者表示，这一程序和相关技术可能会导致严重的不良事件。当前 这项技术是基于适应于TAVR的组织瓣，但不是专门为TAVR设计的。那些可能会受到损害 在卷曲和展开过程中，容易发生骨样钙化沉积，并受到限制 耐用性。在石溪大学和PolyNova心血管公司的合作下，我们开发了 一种新型阀门，专为解决TAVR阀门在使用过程中将遇到的众多挑战而设计 生命周期，从卷曲到部署和在现场的长期表现。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卓越的机械性能，以及(Ii)一种新的设计 用于增强血流动力学、耐久性和抗血栓能力的叶型的优化方法 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。跟随 作为一个成功的第一阶段STTR项目，在第二阶段项目中，我们的目标是扩大我们聚合物阀门的研发活动 迈向第一人，并实施强有力的监管和质量管理体系计划。 拟议的项目包括4个目标：目标1扩展我们的高级计算流动模拟集， 开发第二代瓣膜，开发专用输送导管系统，并扩大我们的瓣膜 产品可以提供一整套阀门通径。AIM 2根据ISO 5840-3(经导管)测试瓣膜性能 ISO10993-1(心脏瓣膜)、ISO 25539-1(心血管植入物)和ISO10993-1(生物兼容性)。我们还将修改我们的 阀门制造能力符合FDA质量管理体系。AIM 3对阀门进行测试 绵羊活体动物模型。这些阀门在急性测试以及慢性10周和20周的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商业计划。 STTR第二阶段项目的组成部分是详细的商业化和监管计划，以此为基础，并在 在这一第二阶段计划的支持下，我们将把PolyNova从一个纯粹的研发车间转变为一个 合格的医疗器械制造商-即建立完全符合cGMP、FDA标准的质量管理体系 包括稳健的设计控制流程。 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。

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.