Cost Effective Trileaflet BioPolymeric Heart Valve For India

目前所有的人工心脏瓣膜都存在血液相容性和血栓栓塞并发症风险方面的问题。印度低成本的Chitra机械心脏瓣膜需要强有力的终身抗凝治疗，这是目前唯一满足印度主要年轻心脏瓣膜患者的瓣膜。因此，大多数印度患者别无选择，只能面临终身抗凝治疗的风险。在印度医院，生物人工心脏瓣膜要么太贵，要么患者不愿意再次手术，因为这些瓣膜的耐久性相对较差，感染率也很高。此外，还存在与使用猪或牛组织有关的个人宗教偏好所引起的关注。由于患者年龄和更严重的耐久性问题，美国微创技术的最新发展对印度没有吸引力。我们需要的是一种低成本的非组织型生物相容性三瓣心脏瓣膜。高分子心脏瓣膜有希望将机械瓣膜和生物瓣膜的优点结合起来。我们的实验室开发了一种新的生物材料，生物聚，它涉及到聚合物材料的工程，在分子水平上，与透明质酸（HA，一种天然存在的多糖）互锁，以制造高度亲水性的血液和生物相容性的聚合物小叶，具有工程合成聚合物的耐久性。初步研究表明，与普通聚合物小叶相比，生物聚小叶具有显著的血液相容性。此外，我们已经证明了将生物聚瓣组装成具有良好血流动力学特性的可植入式三瓣假体的可行性。本R03研究旨在测试和优化Bio-Poly瓣膜作为下一代低成本、高性价比的心脏瓣膜。我们的中心假设是：biopoly是一种有效且低成本的生物材料，用于仅使用阿司匹林抗凝治疗的三叶心脏瓣膜假体。这在三个方面得到了验证。目的1侧重于新瓣膜的血流动力学和耐久性测试，同时优化小叶配合特性。目标2侧重于优化材料制造过程，以最大限度地提高这些瓣膜的血液相容性。目标3侧重于开始动物试验，以验证血液相容性和体内钙化，并为在印度的商业化奠定基础。这些研究是由美国和印度团队与我们的商业伙伴TTK Healthcare合作进行的。TTK Healthcare是印度一家主要的阀门制造商，致力于将我们的低成本技术商业化，以迎合印度市场。我们的方法是创新的，使用了透明质酸，作为一种剂，将血液相容性引入到其他不相容的、耐用的疏水聚合物小叶中，这些小叶具有大规模生产的潜力，成本低，设计公差高。

DESCRIPTION: All present day prosthetic heart valves have issues regarding blood compatibility and risk of thromboembolic complications. India's low cost Chitra mechanical heart valve that requires strong life-long anti-coagulation therapy is the only valve that presently caters to the predominantly young heart valve patient in India. Therefore, most Indian patients have no choice but to face the risks of life long anti-coagulation therapy. Bio-prosthetic heart valves are either too expensive or the patients do not prefer the prospect of re-operation secondary to relatively poor durability of these valves and high rate of infection in Indian hospitals. Further there exists concern arising from personal religious preference related to use of porcine or bovine tissue. Recent development of minimally invasive technology in the United States is not as attractive to India due to the patient age, and more severe durability concerns. What is needed is a low-cost non-tissue based biocompatible tri-leaflet heart valve. Polymeric heart valves have the promise to bring the best of mechanical valves and bio-prosthetic heart valves. Our lab has developed a novel biomaterial, Bio-Poly, which involves the engineering of polymeric materials that are, at a molecular level, interlocked with hyaluronan (HA, a naturally occurring polysaccharide) to make highly hydrophilic hemo- and bio-compatible polymer leaflets with the durability of engineered synthetic polymers. Preliminary work has shown that Bio-Poly leaflets have a remarkably hemo-compatible compared to plain polymer leaflets. Further, we have already demonstrated the feasibility of assembling Bio-Poly leaflets into implantable tri-leaflet valve prosthesis with excellent hemodynamic characteristics. The present R03 study aims to test and optimize Bio-Poly valves as the next generation low-cost and superior heart valve. Our central hypothesis is: that Bio-poly is an effective and low-cost biomaterial for tri-leaflet heart valve prosthesis with aspirin regimen anticoagulation only. This is tested in three aims. Aim 1 focuses on hemodynamic and durability testing of the new valves while optimizing leaflet cooptation characteristics. Aim 2 focuses on optimizing the materials manufacturing process to maximize hemo-compatibility of these valves. Aim 3 focuses on commencing animal trials to validate hemocompatibility and calcification in vivo and lay the groundwork for commercialization in India. These studies are jointly conducted by the US and Indian teams in collaboration with our commercial partner, TTK Healthcare. TTK Healthcare is a major valve manufacturer in India that is committed to commercialize our low-cost technology to cater to the Indian market. Our approach is innovative with the use of HA, as the agent that brings hemo-compatibility to otherwise non-compatible, durable hydrophobic polymer leaflets that have the potential for scaling towards mass production at low-cost and high design tolerance.