ENGINEERED CARDIAC MORPHOGENESIS--STEM CELLS & SCAFFOLDS

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DESCRIPTION: (verbatim) The long term aims of this project are to produce tissue engineered ventricular wall patches for myocardial repair, ventricular assist devices, and eventually replacement ventricles. Our team from academia and industry has expertise in biomaterials, bioreactors, tissue biomechanics, embryonic and somatic stem cells, muscle development, vasculogenesis, extracellular matrix, cardiac injury and regeneration, animal and human heart transplantation. This team will collaborate across three research foci: 1) 'Instructive' tissue scaffolds. Advanced biomaterial fabrication will be used to engineer biodegradable matrices and meshes with controlled pore dimensions, modified with receptor specific molecules. Matrices will be optimized to instruct cell attachment, orientation, migration, proliferation, differentiation, and overall tissue organization. 2) Cell and developmental biology. Primary and stem cell-derived muscle and vascular cells will be studied on modified scaffolds to determine the optimal conditions for producing functional muscle tissue and vascular networks. Engineered tissues will be subjected to mechanical stresses to direct maturation toward in vivo phenotypes. Bioreactors will be developed to implement these requirements on a useful scale. 3) Clinical science and animal models. Contractile ventricular patches will be tested in an injured heart model. Integration with host tissue and restoration of contractile function will be valuated. A tubular cardiac assist organ comprised of vascularized myocardium and endocardium will also be developed. The 'tube hearts' will be conditioned in pulsatile flow circuits, assessed for mechanical performance in vitro, and eventually grafted into aortas of syngeneic rats for in vivo evaluation. Progress toward these goals should establish design principles necessary for constructing more complex ventricular devices.