Engineering of Pacemaker Tissue for Cardiac Implantation

心脏植入起搏器组织工程

• 批准号: 6418038
• 负责人: DOUGLAS BURR COWAN
• 金额: $ 31.57万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-18 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6418038
• 关键词: atrioventricular node; biomaterial compatibility; cell transplantation; collagen; congenital heart disorder; electrical conductance; electronic pacemaker; electrophysiology; gap junctions; heart block; heart function; heart pacemaker tissue; implant; laboratory rat; medical implant science; mesenchyme; muscle satellite cell; myoblasts; nonhuman therapy evaluation; stem cells; striated muscles; tissue /cell culture; tissue engineering

DESCRIPTION (Provided by Applicant): Congenital and surgically-induced block of cardiac atrioventricular (AV) node conduction is a serious long-term clinical problem in pediatric patients. Currently, the permanent implantation of a cardiac pacemaker device is the only therapy available for the treatment of congenital complete heart block and AV block subsequent to surgical repair of inborn heart abnormalities such as ventricular septal defect, AV canal defect, and tetralogy of Fallot. Despite the technological advancements in cardiac pacemaker design and function, permanent pacemaker therapy in infants and children continues to be problematic. Since the survival rate for children that undergo complex surgical procedures to repair congential cardiovascular defects has greatly increased, the need for improved long-term pacing solutions in the pediatric patient population has provided the rationale for this project. The primary goal of the project is to engineer tissue that would act as an electrical conduit from the atrium to the ventricle of the heart for use in patience that lack normal AV node function. The engineered tissue will be comprised of skeletal muscle progenitor cells (myoblasts) or mesenchymal stem cells (bone marrow stromal cells) that can be autologously derived. The cells will be cast in a three dimensional tissue construct using natural polymers, such as collagen, in order to efficiently deliver cells to the AV groove of the heart. Accordingly, in the present proposal, we will address the following specific aims; (a) engineer electrically conductive tissue suitable for cardiac implementation (b) characterize the electromechanical properties of engineered tissue constructs in vitro, (c) determine the practicality of implanting tissue constructs in the cardiac AV groove, and (d) evaluate electrical conduction in hearts implanted with engineered tissue constructs. This is a conceptually simple research project that requires extensive expertise in a number of fields including cell biology, tissue engineering, and electrophysiology. The success of the research depends on a multidisciplinary group of individuals that will apply their knowledge to specific components of the project with the intention of developing a therapy to alleviate a substantial clinical problem. Ultimately, these experiments are intended to provide an alternative or adjunct treatment to conventional cardiac pacemaker therapy.

描述（由申请人提供）：先天性和外科诱导的 心脏房室（AV）结传导是一种严重的长期临床 儿科患者的问题。目前， 心脏起搏器装置是唯一可用于治疗 先天性完全性心脏传导阻滞和房室传导阻滞， 先天性心脏异常，如室间隔缺损、AV管缺损， 和法洛四联症尽管心脏病的技术进步 起搏器设计和功能，婴儿永久性起搏器治疗， 儿童仍然是个问题。因为儿童的存活率 接受复杂的外科手术来修复先天性心血管缺陷 大大增加了对改善长期起搏解决方案的需求， 儿科患者人群为该项目提供了依据。 该项目的主要目标是设计组织， 从心房到心室的电导管，用于 缺乏正常房室结功能的患者。工程组织将 包括骨骼肌祖细胞（成肌细胞）或间充质干细胞 细胞（骨髓基质细胞），可以自体衍生。细胞 将使用天然聚合物浇铸成三维组织结构， 例如胶原蛋白，以便有效地将细胞递送到血管的AV沟。 心 因此，在本提案中，我们将处理以下具体问题 目的;（a）设计适合心脏的导电组织 实现（B）表征工程化的机电特性， （c）确定植入组织的实用性 （d）评估心脏AV沟中的电传导， 植入了工程组织构建体的心脏。 这是一个概念简单的研究项目，需要广泛的 在许多领域，包括细胞生物学，组织工程， 电生理学这项研究的成功取决于多学科的 一群人，将他们的知识应用到特定的组成部分， 该项目旨在开发一种治疗方法， 严重的临床问题。最终，这些实验旨在 为传统心脏起搏器提供替代或辅助治疗 疗法