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）：当今的所有假肢心脏瓣膜都有并发症。机械心脏瓣膜（HVS）需要终身抗凝疗法，而基于固定组织的生物假发心脏瓣膜却困扰着耐用性，免疫原性和钙化问题。聚合心脏瓣膜有望结合最佳的机械阀和最佳生物假心脏瓣膜。我们的实验室开发了一种新型的生物材料，生物耕种，由工程聚合物制成，该聚合物在分子水平上与透明质酸（HA，一种天然存在的多糖）相互关联，以使高度亲水性血液相相的聚合物小叶与工程合成聚合物的耐用性。初步工作表明，相对于普通聚合物小叶，生物耕种的传单具有明显降低的血栓形成潜力。此外，我们已经证明了可行性 制造生物大臣的传单，并将它们组装成可植入的三叶阀。本R01研究旨在通过微调材料组成和加工来衡量生物垄断作为当前心脏瓣膜技术的潜在替代方案，以满足心脏瓣膜小叶的耐用性和抗强化要求。我们的中心假设是：生物耕种HVS为生物假体和机械HV的缺点提供了可行的解决方案。这在三个目标中进行了测试。 AIM 1量化了心脏瓣膜血液动力学性能以及生物poltion瓣心脏瓣膜的耐用性/疲劳特征。 AIM 2的重点是阐明传单组成和加工对血液相容性的影响。 AIM 3专注于理解生物poltion hv的体内血液相容性和钙化特性。该建议由Lakshmi Prasad Dasi博士领导，他是一位受过良好训练的年轻研究者，在心脏瓣膜工程和心血管生物力学方面具有专业知识。共同研究的人是詹姆斯博士，他是一位既定的聚合物材料科学家，也是生物店的发明者。她已成功地在骨科应用程序（目前在欧洲商业上获得）中成功翻译了这种材料； Popat博士的专业知识在于生物兼容和表面纳米工程； Orton博士是经验丰富的兽医外科医生。如果提出的工作表明，生物大都会小叶具有抗雄性，引起出色的血液动力学，耐用，并且表现出对体内钙化的抵抗力，那么这种R01赠款可能会导致对聚合物HV的突破性技术，这些HV的突破性技术需要很少或不需要抗形性，可以使最小的抗击能力足够持久，并且可以持久耐用，以使终于生存时间。