TGA-ethanol Pretreated Bovine Pericardium for the Norwood Procedure

用于诺伍德手术的 TGA-乙醇预处理牛心包

• 批准号: 8013820
• 负责人: Robert J Levy
• 金额: $ 65.51万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8013820
• 关键词: Accounting; Adolescent; Affect; Allografting; Angiography; Animal Euthanasia; Animal Model; Aorta; Biocompatible Materials; Cardiac Catheterization Procedures; Cardiac Surgery procedures; Cattle; Child; Childhood; Devices; Ethanol; Glutaral; Goals; Human; Hypoplastic Left Heart Syndrome; Image; Implant; Inflammation; Instruction; Investigation; Mechanics; Medical Care Costs; Microscopic; Modeling; Morphology; National Heart, Lung, and Blood Institute; Outcome; Pericardial body location; Phase; Physiological; Plant Roots; Procedures; Property; Pulmonary artery structure; Research; Resistance; Sampling; Sheep; Site; Specimen; Staging; Testing; Thrombosis; Tissues; United States; Xenograft procedure; base; biomaterial compatibility; calcification; congenital heart disorder; crosslink; improved; indexing; novel; pericardial sac; preclinical study; programs; repaired

DESCRIPTION (provided by applicant): The Norwood staged repair for hypoplastic left heart syndrome (HLHS) has saved the lives of thousands of children. Stage I of this procedure involves augmenting the underdeveloped aorta, and at present this is done using either cryopreserved human allograft material (pulmonary artery or aorta) or glutaraldehyde pretreated bovine pericardium. The proposed research will investigate using bovine pericardium, pretreated with a novel cross-linker, triglycidylamine (TGA), synthesized by our group. TGA, when used to crosslink heterograft biomaterials, confers stability, biocompatibility, calcification resistance and mechanical properties that are superior to glutaraldehyde, the cross-linker used to prepare clinically used heterograft biomaterials. In addition we will use TGA in combination with ethanol pretreatment, which confers additional calcification resistance. TGA-ethanol pretreated bovine pericardium is hypothesized to be a better candidate material than glutaraldehyde fixed bovine pericardium for Stage I Norwood aortic augmentation because of a number of advantages of TGA cross-linking compared to glutaraldehyde including greater material stability, mechanical properties more comparable to native tissue and calcification resistance. The goal of these investigations is to carry out preclinical studies in a sheep model under GLPs for submission to the FDA for an IDE for a TGA-ethanol pretreated bovine pericardium implant. This will be the basis of our competitive Phase 2 submission following the conclusion of the proposed initial two year NHLBI C-TRIP program. Specific Aim 1. Prepare and characterize TGA-ethanol pretreated bovine pericardium. This material will be compared with the currently manufactured glutaraldehyde pretreated bovine pericardium (control implants). Endpoints will include indices of crosslink stability, microscopic morphology and mechanical properties per unaxial testing. Specific Aim 2. Carry out animal model studies of the Norwood I aortic root augmentation procedure using TGA-ethanol pretreated bovine pericardium versus glutaraldehyde pretreated bovine pericardium (controls) in juvenile sheep with survival to 150 days. Prior to euthanasia animals will undergo a cardiac catheterization and angiography procedure in order to obtain physiologic endpoints and imaging studies of the aortic augmentation site comparing two types of xenograft implants. Specific Aim 3. Explantation at 150 days will be followed by analyses of aortic augmentation specimens for a number of endpoints including macroscopic and microscopic assessment of material integrity, calcification, thrombosis, and inflammation. Calcification analyses will be carried out on explants and samples will also be studied for changes in mechanical properties compared to unimplanted material parameters. RELEVANCE (See instructions): Congenital heart disease affects thousands of children in the United States, and accounts for billions of dollars in medical care costs. This proposal will investigate a new pediatric cardiac surgery device, a TGA-ethanol pretreated bovine pericardial xenograft, that may improve outcomes for the most severe form of congenital heart disease, the hypoplastic left heart syndrome.

描述（由申请人提供）： 诺伍德（Norwood）上演的左心脏综合征（HLHS）的修复挽救了数千名儿童的生命。该过程的第一阶段涉及增加欠发达主动脉，目前使用冷冻保存的人类同种异体移植物材料（肺动脉或主动脉）或戊二醛预处理的牛心包进行。拟议的研究将使用牛心包进行研究，并用新型的交叉链链甘氨酸（TGA）预处理，并由我们的组合成。当TGA用于交叉链接异光生物材料时，赋予稳定性，生物相容性，钙化耐药性和机械性能，这些特性优于戊二醛，这是用于制备临床使用的异光生物材料的交联。此外，我们将使用TGA与乙醇预处理结合使用，从而赋予额外的钙化抗性。假设预处理的牛心包预处理的牛是一种更好的候选材料，这是I型诺伍德主动脉增强的固定牛胸膜，因为与glutaraldehyde相比，与glutaraldehyde相比，TGA交叉链接的许多优势与机械材料稳定性更具可比性的原生物性和成分为基础。这些研究的目的是在GLP下的绵羊模型中进行临床前研究，以便向FDA提交IDE，以供TGA-乙醇预处理的牛心包植入。在拟议的初始两年NHLBI C-Trip计划结束后，这将是我们竞争性第二阶段提交的基础。特定目标1。准备和表征TGA-乙醇预处理的牛心包。该材料将与当前生产的戊二醛预处理的牛心包（对照植入物）进行比较。终点将包括共链接稳定性，微观形态和每个单次测试的机械性能的指标。具体目的2。使用预处理的牛心包对诺伍德I主动脉根的增强手术进行动物模型研究，与少年绵羊的戊二醛预处理的牛心包（对照），生存期至150天。在安乐死之前，动物将进行心脏导管插入术和血管造影程序，以获取比较两种类型的异种移植物植入物的主动脉增强部位的生理终点和成像研究。特定的目标3。在150天后的外观将分析主动脉增强标本，以分析许多终点，包括材料完整性，钙化，血栓形成和炎症的宏观和显微镜评估。与未植入物质参数相比，还将在外植体上进行钙化分析，并研究样品以进行机械性能的变化。 相关性（请参阅说明）：先天性心脏病会影响美国成千上万的儿童，并占医疗费用数十亿美元。该提案将研究一种新的儿科心脏手术装置，即预处理的牛心包异种移植物，可以改善最严重的先天性心脏病形式的结果，即低可爱的左心综合征。