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

项目摘要 先天性心脏病（CHD）是由出生时发生的心脏结构缺陷引起的， 流经心脏和身体其他部位CHD影响大约1,000个活产婴儿中的10个， 在出生后的第一年内需要进行干预或手术。大约100万儿童和140万 在美国，成年人患有CHD，每年进行超过182，000例心脏瓣膜置换术。目前， 可用的心脏瓣膜假体不能作为天然心脏组织工作 它们的耐久性和支持组织再生的能力。此外，他们还与 并发症，如凝块、血栓形成和血栓栓塞的风险增加、钙化和感染。 生物假体瓣膜的置换通常需要复杂且高风险的手术，并且对患者造成经济损失。 美国每年为医疗保健系统带来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点 瓣膜（TEHV）是使用模拟人体组织的支架制造的。通过内源性组织生长， Neoolife的仿生肺动脉心脏瓣膜被广泛增强或最终被替换， 与CHD儿科患者一起生长的自体和功能性瓣叶是耐用的， 血栓形成的这些仿生瓣膜不需要终生的血液稀释剂治疗， 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分 沉积（DCD）技术，获得更均匀的仿生支架沉积。仿生 将使用新的多阶段处理装置制造肺动脉心脏瓣膜原型（n=10）。的 将在体外测试原型的机械和功能特性，并在体内进行评估（n=5，180 天）以评价聚合物降解、细胞化、生物力学和瓣膜功能。 在II期，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开发的肺动脉心脏瓣膜有资格获得人道主义器械 用于治疗儿童CHD的豁免（HDE）指定。

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.