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）：目前所有人工心脏瓣膜都存在并发症。机械心脏瓣膜（HV）需要终身抗凝治疗，而基于固定组织的生物人工心脏瓣膜则受到耐久性、免疫原性和钙化问题的困扰。聚合物心脏瓣膜有望联合收割机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生物材料BioPoly，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瓣叶。初步工作表明，相对于普通聚合物瓣叶，BioPoly瓣叶显着降低了血栓形成的可能性。此外，我们已经证明了 制造BioPoly瓣叶并将其组装成可植入的三叶瓣膜。本R 01研究旨在通过微调材料成分和加工以满足心脏瓣膜瓣叶的耐久性和抗血栓形成要求，评估BioPoly作为当前心脏瓣膜技术潜在替代品的有效性。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。这在三个目标中得到检验。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/疲劳特征。目的2着重阐明瓣叶组成和处理对血液相容性的影响。目标3重点关注了解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人员，拥有心脏瓣膜工程和心血管生物力学方面的专业知识。詹姆斯博士是一位知名的聚合物材料科学家，也是BioPoly的发明者。她成功地将这种材料转化为骨科应用（目前在欧洲有市售）; Popat博士的专业知识在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瓣叶HV具有抗血栓形成性，引起良好的血液动力学，耐用，并证明对体内钙化的抵抗力，则该R 01资助可能会导致聚合物HV的突破性技术，这些技术需要很少或不需要抗凝，可以微创输送，并且足够耐用，可以终身使用。