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

开发用于治疗小儿先天性心脏病的仿生无支架肺心瓣膜

• 批准号: 10696291
• 负责人: Garrett N Coyan
• 金额: $ 55.38万
• 依托单位: NEOOLIFE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10696291
• 关键词: Address; Adult; Affect; Animal Model; Anticoagulants; Aorta; Autologous; Biocompatible Materials; Biomechanics; Biomimetic Materials; Biomimetics; Bioprosthesis device; Birth; Blood flow; Cardiac; Cardiac Surgery procedures; Cells; Child; Childhood; Chronic; Clinical; Coagulation Process; Collaborations; Complex; Congenital Abnormality; Coupling; Defect; Deposition; Development; Devices; Echocardiography; Economic Burden; Engineering; Epitopes; Evaluation; Failure; Freedom; Growth; Healthcare Systems; Heart; Heart Valve Prosthesis; Heart Valves; Histologic; Hospital Costs; Hospitalization; Implant; In Vitro; Infection; Infiltration; Intervention; Legal patent; Life; Lung; Marketing; Mechanics; Methods; Newborn Infant; Operative Surgical Procedures; Patients; Phase; Physiological; Polymers; Polyurethanes; Procedures; Process; Property; Prosthesis; Protocols documentation; Pulmonary valve structure; Qualifying; Quality of life; Repeat Surgery; Resistance; Rest; Risk; Small Business Technology Transfer Research; Spatial Distribution; Structural defect; Structure; Surgeon; Surgical Valves; Technology; Testing; Thick; Thromboembolism; Thrombosis; Thrombus; Tissues; Universities; biomechanical test; bioprocess; calcification; cardiac tissue engineering; congenital heart disorder; cost; design; heart valve replacement; hemodynamics; high risk; human tissue; implantation; improved; in vitro testing; in vivo; in vivo evaluation; manufacture; neglect; operation; pediatric patients; prototype; pulmonary valve replacement; regeneration potential; scaffold; sheep model; success; therapy development; thrombogenesis; tissue regeneration; valve replacement

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.

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 流过心脏和身体的其余部分。 CHD影响1000名活出生的孩子中约有10个，其​​中25％ 这将需要在生命的第一年内进行干预或手术。约100万儿童和140万 成人在美国居住在冠心病中，每年进行超过182,000个心脏瓣膜更换。现在， 可用的心脏瓣膜假体不作为本地心脏组织的性能，并且有几个限制 它们的耐用性和支持组织再生的能力。此外，它们与 并发症，例如凝块，血栓形成和血小板主义的风险增加，钙化和感染。 更换生物假体阀通常需要复杂而高风险的操作，并构成经济 美国每年对医疗保健系统的$ 1.7B负担。 Neoolife旨在通过发展组织工程心脏来克服CHD治疗中的这些主要缺点 使用模仿人体组织的支架制造的阀（TEHV）。通过内源性组织生长， Neoolife的仿生肺心脏瓣膜被广泛增强或最终更换，离开 自体和功能性传单与二氧化构冠心儿科患者一起生长，耐用且不 - 血栓形成。这些仿生瓣不需要终身的血液稀释剂，并且对 钙化和感染。在此STTR I阶段项目中，Neoolife将修改其专有的双重组件 沉积（DCD）技术以获得更均匀的仿生支架沉积。仿生 肺心瓣原型（n = 10）将使用新的多个阶段处理设置制造。这 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 几天）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开发的肺心瓣有资格获得人道主义装置 豁免（HDE）设计用于治疗小儿冠心病。