Hyaluronan enhanced polymeric heart valve prosthesis

透明质酸增强型聚合物人工心脏瓣膜

• 批准号: 9251521
• 负责人: Lakshmi Prasad Dasi
• 金额: $ 3.19万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-16 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251521
• 关键词: Address; Adolescent; Anticoagulation; Area; Artificial Heart; Biocompatible Materials; Biomechanics; Bioprosthesis device; Blood; Blood Platelets; Calcified; Cardiovascular system; Cell Proliferation; Characteristics; Clinical; Data; Endothelial Cells; Engineering; Environment; Europe; Family suidae; Fatigue; Future; Goals; Gold; Grant; Heart Valve Prosthesis; Heart Valves; Human; Hyaluronan; Hydrophobicity; In Vitro; Lead; Length; Leukocytes; Life; Liquid substance; Lung; Mechanics; Methods; Modeling; Molecular; Motion; Orthopedics; Performance; Plague; Polyethylenes; Polymers; Polysaccharides; Positioning Attribute; Procedures; Process; Property; Publishing; Research Personnel; Research Project Grants; Resistance; Risk; Scientist; Sheep; Stents; Surface; Surgeon; Techniques; Technology; Testing; Thrombus; Tissues; Training; Translating; Universities; Whole Blood; Work; base; biomaterial compatibility; calcification; crosslink; density; design; experience; experimental study; flexibility; heart valve replacement; hemodynamics; hydrophilicity; immunogenic; improved; in vivo; innovation; macrophage; materials science; mechanical properties; member; minimally invasive; monocyte; nanoengineering; new technology; novel; public health relevance; response

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.

描述（由申请人提供）：目前所有的人工心脏瓣膜都存在并发症。机械心脏瓣膜（HV）需要终生抗凝治疗，而基于固定组织的生物假体心脏瓣膜则存在耐久性、免疫原性和钙化问题。聚合物心脏瓣膜有望结合最好的机械瓣膜和最好的生物假体心脏瓣膜。我们的实验室开发了一种新型生物材料 BioPoly，它由工程聚合物制成，在分子水平上与透明质酸（HA，一种天然存在的多糖）互锁，以制造具有工程合成聚合物耐久性的高度亲水性血液相容性聚合物小叶。初步研究表明，与普通聚合物小叶相比，BioPoly 小叶显着降低了血栓形成的可能性。此外，我们已经论证了可行性 制造 BioPoly 小叶并将其组装成植入式三叶瓣膜。目前的 R01 研究旨在通过微调材料成分和加工来衡量 BioPoly 作为当前心脏瓣膜技术的潜在替代品的功效，以满足心脏瓣膜小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 的缺点提供了可行的解决方案。这是在三个目标上进行测试的。目标 1 量化 BioPoly 心脏瓣膜的心脏瓣膜血流动力学性能和耐用性/疲劳特性。目标 2 侧重于阐明传单成分和加工对血液相容性的影响。目标 3 侧重于了解 BioPoly HV 的体内血液相容性和钙化特性。该提案由 Lakshmi Prasad Dasi 博士领导，他是一位训练有素的年轻研究员，在心脏瓣膜工程和心血管生物力学方面拥有专业知识。共同研究人员包括 James 博士，他是一位著名的高分子材料科学家，也是 BioPoly 的发明者。她已成功地将这种材料转化为骨科应用（目前已在欧洲上市）； Popat 博士，专长于生物相容性和表面纳米工程；奥顿博士是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、引发优异的血流动力学、耐用并表现出抗体内钙化的能力，那么这项 R01 资助可能会带来聚合物 HV 的突破性技术，该技术几乎不需要或不需要抗凝，可以微创方式输送并且足够耐用，可以终生使用。