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: 10318136
• 负责人: David Kalfa
• 金额: $ 56.21万
• 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/10318136
• 关键词: Acute; Adult; Aorta; Area; Biodegradation; Bioprosthesis device; Caliber; Cardiac; Cardiac Surgery procedures; Child; Childhood; Competence; Computer Models; Computers; Data; Development; Devices; Engineering; Equilibrium; Extracellular Matrix; Failure; Fatigue; Fostering; Future; Generations; Goals; Growth; Health; Health Care Costs; Heart Valve Diseases; Heart Valves; Height; Implant; In Vitro; Infant; Inflammation; Lead; 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; Property; Prosthesis; Public Health; Quality of life; Rattus; Repeat Surgery; Research; Research Personnel; Risk; Scanning Electron Microscopy; Scientist; Sheep; Spectrum Analysis; Stress; Stretching; Structure; Surgeon; Surgical Valves; Techniques; Testing; Thick; Time; Tissue Engineering; Tube; United States National Institutes of Health; Universities; Validation; Ventricular; base; biomaterial compatibility; calcification; congenital heart disorder; cytotoxicity test; density; design; hemodynamics; implantable device; implantation; in vivo; innovation; mechanical properties; mortality; multidisciplinary; neonate; preclinical study; pressure; process optimization; 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.

项目综述：超过1.6万名美国儿童需要植入带瓣管道来替代右眼 每年的心室流出道(RVOT)。这些儿童需要一到四次重复的心内直视手术 在成年之前更换带瓣管道，因为可用的假体不会随着孩子的成长而生长。 我们多学科协作团队的长期目标是开发一种生物稳定的聚合物带瓣管道。 可以通过手术植入重建RVOT，然后(通过连续的经导管)进行扩张 程序)，以避免对儿童进行多次手术。我们的总体目标是设计、验证和演示 体外和体内对该装置的可扩充性和瓣膜功能的概念证明。我们的中央 假说是使用和控制加工具有足够塑性的生物稳定聚合物，相关 对于阀门的优化设计，可以在保持阀门的同时允许连续可控的扩张 能力。我们将在以下三个具体目标中检验这一假设：Aim1：表征增长 无阀门管道的通达性。我们将对8 ePTFE的力学性能进行表征 使用单轴拉伸试验机的不同密度和厚度的材料，1.2)开发了一种计算 根据力学数据建立了12-24 mm的扩径模型，并对扩径进行了验证 使用经导管球囊实验并测量扩张潜力、单轴拉伸性能 和微体系结构。目标2：开发一种适用于所有通径的阀门设计。我们的假设是一个 增加粘合高度和增加自由边缘长度的阀门设计可以从 直径12-24 mm，同时保持阀门能力。我们将使用基于流固耦合的 我们的心脏瓣膜脉冲复制器的计算设计、原型制造和实验验证 反复检查设计对带瓣管道血流动力学性能的影响。目标3： 描述阀门管道的性能和耐用性。我们将对生物兼容性进行表征 使用大鼠主动脉模型；3.2)在绵羊模型中演示急性活体表现；3.3)评估 加速磨损试验机中的体外耐久性。预期结果：已经确定了 制造工艺，针对不同的膨胀阶段优化阀门流体动力学，并在 生物相容性、扩张性和瓣膜功能维持概念的体内外验证 该设备的。这项研究的创新之处在于，我们将开发一种设计成带阀门的管道 专门针对增长-在扩张的每个阶段都是耐用和有能力的住宿，使用和 开发创新的设计、计算模型、制造技术和翻译 方法论。影响和意义：我们的结果将有助于进一步开发 创新的可扩展外科瓣膜装置，将有助于避免多次重复的儿童心脏直视手术。 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。