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）已成为未满足的有效治疗方法 严重主动脉瓣狭窄（AS）患者不能手术的临床需求。TAVR近期纵向随访研究 然而，患者指出，该手术和相关技术可能导致严重的不良事件。电流 该技术基于适用于TAVR的组织瓣膜，但不是专门为TAVR设计的。那些可能会受到伤害 在卷曲和展开过程中，易受“骨样”钙化沉积的影响， 耐久性在斯托尼布鲁克大学和波利诺瓦心血管公司的合作中，我们已经开发 一种新型瓣膜，专门设计用于解决TAVR瓣膜在其植入过程中遇到的众多挑战。 生命周期，从压接到部署和长期原位性能。它结合了（i）新颖的聚合物技术， xSIBS，其结合了上级生物稳定性和优异的机械性能，和（ii）新颖的设计 优化瓣叶轮廓的方法，以增强血液动力学、耐久性和抗血栓性 性能 我们的广泛目标是开发一种可行且耐用的TAVR瓣膜，为现有的TAVR瓣膜提供真实的替代方案。 生物假体主动脉瓣，并允许长期解决方案适用于更广泛的人群。以下 作为一个成功的一期STTR项目，在二期项目中，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，并实施一个强大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扩展我们的先进计算流模拟集， 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 我们的产品适用于一整套阀门通径。目标2根据ISO 5840-3（经导管）测试瓣膜性能 心脏瓣膜）、ISO 25539-1（心血管植入物）和ISO 10993 -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， 绵羊体内模型。在急性试验以及10周和20周的慢性试验中，对瓣膜的有效性和安全性进行了试验。 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， 在第二阶段计划的支持下，我们将把PolyNova从一个纯粹的研发商店转变为一个公司， 合格的医疗器械制造商-即具有完全符合cGMP、FDA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导致主动脉瓣疾病治疗的突破， 提供负担得起的、长期的、微创的解决方案， 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.