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.
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