Development of a Biomimetic Stentless Pulmonary Heart Valve for the Treatment of Pediatric Congenital Heart Disease

项目总结 先天性心脏病(CHD)是由出生时心脏结构缺陷引起的，这些缺陷会影响血液。 流经心脏和身体的其他部分。每1000名活产儿童中约有10人患有先天性心脏病，25% 这需要在他们生命的第一年内进行干预或手术。大约100万儿童和140万儿童 在美国，成年人患有冠心病，每年进行超过18.2万例心脏瓣膜置换手术。目前， 现有的心脏瓣膜假体不像天然心脏组织那样工作，并且有几个与以下方面相关的限制 它们的耐用性和支持组织再生的能力。此外，它们还与 并发症，如血栓、血栓形成和血栓栓塞症、钙化和感染的风险增加。 替换生物瓣膜往往需要复杂和高风险的手术，并构成经济上的 美国每年给医疗保健系统带来17亿美元的负担。 Neoolife旨在通过开发组织工程心脏来克服CHD治疗中的这些主要缺陷 瓣膜(TEHV)是使用模仿人体组织的支架制造的。通过内源组织生长， Neoolife的仿生肺心脏瓣膜被广泛增强或最终被取代，留下 与CHD儿科患者一起生长的自体和功能叶是耐用的和非 会引发血栓。这些仿生瓣膜不需要终生血液稀释剂治疗，并能抵抗 钙化和感染。在这个STTR第一阶段项目中，Neoolife将修改其专有的双组件 沉积(DCD)技术可以获得更加均匀的仿生支架沉积。仿生学 肺心脏瓣膜原型(n=10)将使用新的多阶段加工装置来制造。这个 原型将在体外测试其机械和功能特性，并在体内进行评估(n=5,180 天)，以评估聚合物降解、细胞化、生物力学和瓣膜功能。 在第二阶段，将进行进一步的体外和体内研究，以提供足够的技术信息 证明Neoolife开发的肺心瓣膜有资格获得人道主义装置 儿科CHD治疗的豁免(HDE)称号。

PROJECT SUMMARY Congenital heart disease (CHD) is caused by defects in the heart structure that occur at birth and affect blood flow through the heart and the rest of the body. CHD affects around 10 out of 1,000 live-born children, 25% of which will need an intervention or surgery within their first year of life. Circa 1 million children and 1.4 million adults live with CHD in the US, and over 182,000 heart valve replacements are performed every year. Currently, available heart valve prostheses do not perform as native cardiac tissue and have several limitations related to their durability and ability to support tissue regeneration. In addition, they have been associated with complications such as clots, increased risk of thrombosis and thromboembolism, calcification, and infection. Replacement of bioprosthetic valves often requires complex and high-risk operations and poses an economic burden of $1.7B in the US per year to the healthcare system. Neoolife aims to overcome these major drawbacks in CHD therapy by developing tissue engineered heart valves (TEHVs) that are fabricated using scaffolds that mimic human tissue. Through endogenous tissue growth, Neoolife’s biomimetic pulmonary heart valves are extensively augmented or eventually replaced, leaving autologous and functional leaflets that grow with the CHD pediatric patient that are durable and non- thrombogenic. These biomimetic valves do not require life-long blood thinner treatments and are resistant to calcification and infection. In this STTR Phase I project, Neoolife will modify its proprietary Double Component Deposition (DCD) technology to obtain a more homogeneous biomimetic scaffold deposition. Biomimetic pulmonary heart valve prototypes (n=10) will be fabricated using a new multiple stage processing setup. The prototypes will be tested in vitro for their mechanical and functional properties and assessed in vivo (n=5, 180 days) to evaluate polymer degradation, cellularization, biomechanics, and valve function. In Phase II, further in vitro and in vivo studies will be performed to provide sufficient technical information to demonstrate that Neoolife developed pulmonary heart valve qualifies for obtaining a Humanitarian Device Exemption (HDE) designation for the treatment of pediatric CHD.