Restoring LV Function Post-MI Using Fibrin-Gel Based Engineered Myocardium

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DESCRIPTION (provided by applicant): Cardiovascular disease can lead to myocardial infarction (Ml) and subsequent heart failure. There are currently a number of therapies aimed at preventing or treating heart failure post-Mi. Only heart transplantation replaces infarcted myocardium to restore heart function, but there is a paucity of donor hearts and the incidence of cardiovascular disease continues to rise. A new and innovative option is the use of "heart patches" created in vitro for implantation in vivo. The research proposed here aims to address 3 critical issues pertaining to the function and eventual use of such heart patches - 1) the effect of cellular composition on the contraction force and construct mechanical stability, 2) the effect of a biomimetic culture environment on tissue morphology and function, and 3) the efficacy of myocardial equivalents biomimetically-engineered in vitro in restoring left ventricular function post-Mi. The overall hypothesis of this work is that myocardium engineered in vitro in biomimetic culture conditions restores post-Mi left ventricular function better than cell therapy-based methods of repair. The environment at the University of Minnesota uniquely positions me to address this hypothesis, as the world-renowned Lillehei Heart Institute and the Center for Cardiac Repair are both located nearby and have been home to past collaborators with our lab. This opportunity affords me the ability to augment my already considerable background in tissue mechanics with tissue engineering methods as well as cardiac anatomy and physiology in health and disease. My career plan includes gaining considerable expertise in cell and tissue culture techniques, bioreactor development, as well as surgical techniques and physiological evaluation in a rat model of MI during the mentored phase. I will then leverage these skills to directly compare the efficacy of myocardial tissue engineered in vitro with current cell-therapy based methods of cardiac repair in restoring function to the left ventricle post-Mi during the independent phase. This research is especially critical considering the continuing rise in incidence of heart disease. The results of this research may help elucidate design parameters that are critical to the creation of functional myocardium engineered in vitro and thus advance the goal of the "heart patch" closer to reality. RELEVANCE (See instructions): The relevance of this research proposal regards the study of a high potential method for functional repair of the heart during heart failure. This research is especially critical considering the continuing rise in incidence of heart disease. The proposed research aims to elucidate critical design parameters in the creation and culture of heart tissue engineered in the lab and to find way to improve this tissue's efficacy in restoring functionality to the injured heart.