This training grant is designed to provide the principal investigator (PI) with the necessary didactic and technical training to be come an independent biomedical engineer. The PI has the immediate career goals of obtaining a base of knowledge in cell development and molecular biology sufficient to allow the establishment of a program in tissue engineering. The long-term career goals are to gain the knowledge and experience necessary to become a highly competitive biomedical engineer leading a multidisciplinary team developing tissue engineered prosthetic devices that can be successfully implemented in the clinical setting. The career development plan is designed to provide the theoretical background information in the biological and clinical sciences necessary to contribute to the conduct of high quality biomedical and bioengineering research. Congenital malformations are present in approximately 1% of all live births and are evident in a significant percentage of spontaneous abortions. The architecture of the myocardium is most commonly altered in the developing embryo by an atrial or ventricular septal defect or a related congenital malformation of the muscular septum. Technology leading to the development of cell-based prosthetic devices is critical to the repair and restoration of function for these types of defects. The objective of this proposal is to engineer a cell-based prosthesis that can be used to restore structure and function to a segment of dysfunctional myocardium.
The specific aims of the proposal are to: Design and develop a process to fabricate biodegradable collagen substrates. These substrates will provide temporary support for and promote the self-assembly of three-dimensional cell cultures; Determine the optimal conditions for the production of a three-dimensional, histotypic culture of cardiac myocytes and fibroblasts; Modify the reaction vessel to allow mechanical stimulation during culture; Characterize the engineered cardiac muscle implants with respect to intact tissue using morphometric, biochemical, physiological, and molecular techniques; and finally, transplant the engineered tissue in vivo and characterize the mechanical properties, inflammatory response, how well the implant is integrated, remodeled and vascularized by the surrounding native tissue.
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