Hyaluronan enhanced polymeric heart valve prosthesis

描述(申请人提供)：目前所有的人工心脏瓣膜都有并发症。机械瓣膜(HV)需要终生抗凝治疗，而基于固定组织的生物瓣膜存在耐用性、免疫原性和钙化问题。聚合物心脏瓣膜承诺结合最好的机械瓣膜和最好的生物人工心脏瓣膜。我们的实验室开发了一种新型的生物材料BioPoly，它由工程聚合物制成，在分子水平上与透明质酸(HA，一种自然产生的多糖)互锁，以制造具有工程合成聚合物耐用性的高度亲水的血液相容性聚合物小叶。初步工作表明，与普通聚合物叶相比，BioPoly叶显著降低了血栓形成潜力。此外，我们已经论证了这种方法的可行性。 制造BioPoly的小叶并将它们组装成可植入的三叶瓣。目前的R01研究旨在评估BioPoly作为当前心脏瓣膜技术的潜在替代品的有效性，方法是微调材料成分和工艺，以满足心脏瓣膜叶的耐用性和抗血栓形成要求。我们的中心假设是：BioPoly HV为生物假体和机械HV的缺点提供了一种可行的解决方案。这在三个目标上得到了检验。目的1量化心脏瓣膜的血流动力学性能和BioPoly心脏瓣膜的耐久性/疲劳特性。目的2重点阐明小叶成分和炮制对血液相容性的影响。目的3了解BioPoly HV的体内血液相容性和钙化特性。这项建议由拉克希米·普拉萨德·达西博士领导，他是一名训练有素的年轻研究员，拥有心脏瓣膜工程和心血管生物力学方面的专业知识。共同研究人员包括詹姆斯博士，他是一位知名的聚合物材料科学家，也是BioPoly的发明者。她已成功地将这些材料翻译到以下领域：Popat博士，其在生物兼容性和表面纳米工程方面的专长；Orton博士，一位经验丰富的兽医心胸外科医生。如果拟议的工作证明BioPoly小叶HV具有抗血栓形成作用、产生出色的血流动力学、耐用并显示出对体内钙化的抵抗，这项R01拨款可能会导致聚合物HV的突破性技术，这些HV几乎不需要或不需要抗凝，可以最小限度地侵入性输送，并且足够耐用，足以持续一生。

DESCRIPTION (provided by applicant): All present day prosthetic heart valves suffer from complications. Mechanical heart valves (HVs) require life-long anti-coagulation therapy, while bioprosthetic heart valves based on fixed tissue are plagued with durability, immunogenic and calcification issues. Polymeric heart valves promise to combine the best of the mechanical valves and the best of the bioprosthetic heart valves. Our lab has developed a novel biomaterial, BioPoly, made of engineering polymers that are, at a molecular level, interlocked with hyaluronan (HA, a naturally occurring polysaccharide) to make highly hydrophilic hemocompatible polymer leaflets with the durability of engineered synthetic polymers. Preliminary work has shown that BioPoly leaflets have remarkably reduced thrombogenic potential relative to plain polymer leaflets. Further, we have already demonstrated the feasibility of manufacturing BioPoly leaflets and assembling them into an implantable trileaflet valve. The present R01 study aims to gauge the efficacy of BioPoly as a potential alternative to current heart valve technology by fine tuning material composition and processing to meet the durability and antithrombogenic requirements for heart valve leaflets. Our central hypothesis is: BioPoly HVs offer a viable solution to the drawbacks of both bioprosthetic and mechanical HVs. This is tested in three aims. Aim 1 quantifies heart valve hemodynamic performance and the durability/fatigue characteristics of BioPoly heart valves. Aim 2 focuses on elucidating the effects of leaflet composition and processing on hemocompatibility. Aim 3 focuses on understanding the in vivo hemocompatibility and calcification properties of BioPoly HV. This proposal is led by Dr. Lakshmi Prasad Dasi, who is a well-trained young investigator with expertise in heart valve engineering and cardiovascular biomechanics. Co-investigators are Dr. James, who is an established polymer materials scientist, and the inventor of BioPoly. She has successfully translated this material in orthopedic applications (currently commercially available in Europe); Dr. Popat whose expertise lies in bio-compatibility and surface nano-engineering; and Dr. Orton an experienced Veterinary cardiothoracic surgeon. If the proposed work demonstrates that BioPoly leaflet HVs are antithrombogenic, elicit excellent hemodynamics, are durable, and demonstrate resistance to in vivo calcification, this R01 grant may lead to breakthrough technology for polymeric HVs that require little or no anticoagulation, can be delivered minimally invasively and are durable enough to last a lifetime.