An expandable polymeric valved conduit to repair congenital heart disease

用于修复先天性心脏病的可扩张聚合物带阀导管

• 批准号: 10521288
• 负责人: David Kalfa
• 金额: $ 55.7万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-15 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10521288
• 关键词: Acceleration; Acute; Adult; Aorta; Area; Biodegradation; Bioprosthesis device; Cardiac; Cardiac Surgery procedures; Child; Childhood; Competence; Computer Models; Computers; Data; Development; Devices; Diameter; Engineering; Equilibrium; Extracellular Matrix; Failure; Fatigue; Fostering; Future; Generations; Goals; Growth; Health Care Costs; Health protection; Heart Valve Diseases; Heart Valves; Height; Implant; In Vitro; Infant; Inflammation; Length; Life Expectancy; Liquid substance; Maintenance; Measures; Mechanics; Membrane; Methodology; Mission; Modeling; Morbidity - disease rate; Neonatal; Operative Surgical Procedures; Outcome; Patients; Performance; Physiologic pulse; Polymers; Polytetrafluoroethylene; Procedures; Process; Property; Prosthesis; Public Health; Quality of life; Rattus; Repeat Surgery; Research; Research Personnel; Risk; Scanning Electron Microscopy; Scientist; Sheep; Spectroscopy, Fourier Transform Infrared; Stress; Stretching; Structure; Surgeon; Surgical Valves; Techniques; Testing; Thick; Time; Tissue Engineering; Tube; United States National Institutes of Health; Universities; Validation; Ventricular; biomaterial compatibility; calcification; congenital heart disorder; cytotoxicity test; design; fabrication; hemodynamics; implantable device; implantation; in vivo; innovation; manufacture; mechanical properties; mortality; multidisciplinary; neonate; preclinical study; pressure; prototype; repaired; residence; sheep model; skills; subcutaneous; thrombotic complications

Project Summary: More than 16,000 US children need the implantation of a valved conduit to replace the right ventricular outflow tract (RVOT) annually. These children require one to four repeat open-heart surgeries to replace the valved conduit before they reach adulthood because available prostheses do not grow with the child. The long-term goal of our multidisciplinary collaborative team is to develop a biostable polymeric valved conduit that can be implanted surgically to reconstruct the RVOT and then expanded (by successive transcatheter procedures) to avoid multiple surgeries in children. Our overall objective is to design, validate and demonstrate the in vitro and in vivo proof of concept of the expandability and valvar competence of the device. Our central hypothesis is that the use and controlled processing of a biostable polymer with adequate plasticity, associated to an optimized design of the valve, can allow for successive controlled expansions while maintaining valve competence. We will test this hypothesis in the following three specific aims: Aim1: Characterize the growth accommodation of non-valved conduits. We will 1.1) characterize the mechanical properties of 8 ePTFE materials with varying densities and thicknesses using a uniaxial tensile tester, 1.2) develop a computational model of tube expansion from 12-24 mm based on the mechanical data, and 1.3) validate the expansion experimentally using a transcatheter balloon and measuring the expansion potential, uniaxial tensile properties and microarchitecture. Aim 2: Develop a valve design for competence at all diameters. Our hypothesis is that a valve design with increased height of coaptation and increased length of the free edge can be expanded from a 12-24 mm diameter while maintaining valve competence. We will use a fluid-structure interaction based computational design, prototype fabrication, and experimental validation in our heart valve pulse duplicator to iteratively examine the effects of the design on the hemodynamic performance of the valved conduit. Aim 3: Describe the performance and durability of the valved conduit. We will 3.1) characterize the biocompatibility using an aortic rat model; 3.2) demonstrate the acute in vivo performance in a sheep model; 3.3) assess the in vitro durability in an accelerated wear tester. Expected outcomes: to have identified the conditions of the fabrication process, optimized the valve hydrodynamics for different stages of expansion and performed the in vitro and in vivo proof of concept of the biocompatibility, expandability and maintenance of the valvar competence of the device. The innovation of the proposed research is that we will develop a valved conduit designed specifically for growth-accommodation that is durable and competent at every stage of expansion, using and developing innovative designs, computational models, manufacturing techniques and translational methodologies. Impact and significance: our results will contribute to the evidence for further development of an innovative expandable surgical valved device that will help avoid multiple repeat open-heart surgeries in children. Future studies include cytotoxicity testing and a pre-clinical study to prepare FDA approval.

项目概要：超过 16,000 名美国儿童需要植入带阀导管来替代右耳 每年一次心室流出道（RVOT）。这些孩子需要一到四次重复的心脏直视手术才能 在成年之前更换带阀门的导管，因为现有的假肢不会随着孩子的成长而生长。 我们的多学科协作团队的长期目标是开发生物稳定的聚合物阀门导管 可以通过手术植入以重建 RVOT，然后进行扩张（通过连续经导管 程序）以避免儿童多次手术。我们的总体目标是设计、验证和演示 该装置的可扩展性和瓣膜能力的体外和体内概念证明。我们的中央 假设是具有足够可塑性的生物稳定聚合物的使用和受控加工，与 阀门的优化设计，可以允许连续受控膨胀，同时保持阀门 权限。我们将在以下三个具体目标中检验这一假设： 目标 1：描述增长特征 容纳无阀门导管。我们将 1.1) 表征 8 ePTFE 的机械性能 使用单轴拉伸试验机测试具有不同密度和厚度的材料，1.2）开发计算方法 基于机械数据的 12-24 mm 管扩张模型，以及 1.3) 验证扩张 实验性地使用经导管球囊并测量扩张潜力、单轴拉伸特性 和微架构。目标 2：开发适合所有直径的阀门设计。我们的假设是 具有增加的接合高度和增加的自由边缘长度的阀门设计可以从 直径为 12-24 毫米，同时保持阀门性能。我们将使用基于流固耦合的 我们的心脏瓣膜脉冲复制器中的计算设计、原型制造和实验验证 反复检查设计对带阀导管的血流动力学性能的影响。目标 3： 描述带阀导管的性能和耐用性。我们将3.1）表征生物相容性 使用主动脉大鼠模型； 3.2）在绵羊模型中展示急性体内表现； 3.3）评估 加速磨损测试仪中的体外耐久性。预期成果：确定了 制造工艺，优化了不同膨胀阶段的阀门流体动力学，并进行了in 生物相容性、可扩展性和瓣膜能力维持的体外和体内概念证明 设备的。本研究的创新之处在于我们将开发一种设计的带阀导管 专门针对在扩张、使用和使用的每个阶段都持久且有能力的增长住宿 开发创新设计、计算模型、制造技术和转化 方法论。影响和意义：我们的结果将为进一步发展提供证据 创新的可扩张手术瓣膜装置将有助于避免儿童多次重复进行心脏直视手术。 未来的研究包括细胞毒性测试和临床前研究，以准备 FDA 的批准。