(6ce) Cardiac Tissue Engineering Using Embryonic Stem Cell Derived Cardiomyocytes and Novel Biomaterials

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My future research program will combine my unique expertise in chemical engineering fundamentals, biomaterials, stem cell biology, and cardiac electrophysiology. The long-term goals are (1) determine the effects of material properties, controlled drug delivery, and mechanical and electrical stimuli on stem cells and use this knowledge to design systems for large-scale cell differentiation, (2) improve the electrophysiological function of tissue engineered cardiac grafts by influencing tissue structure and cellular interconnectivity and (3) create materials that will enhance re-endothelialization of the diseased or damaged vascular wall through specific interactions with endothelial and endothelial progenitor cells. I intend to explore the relationship between scaffold material properties and cellular function, including gene expression, differentiation, proliferation, and migration. Potential funding sources for these efforts include the NIH, NSF, and American Heart Association.

This research plan is the culmination of my doctoral work in chemical engineering at Rice University and my undergraduate and post-doctoral work in biomedical engineering at Johns Hopkins University. During my graduate research, I showed that nitric oxide-generating hydrogels influenced key components of the restenosis cascade both in vitro and in vivo. Localized drug delivery was achieved at the site of vascular injury using these poly(ethylene glycol) copolymers, which can be rapidly photopolymerized in situ. These materials can be tailored to provide cell-type specific adhesion ligands, degrade in response to cellular enzymes, and present immobilized growth factors. My postdoctoral research focuses on the differentiation of cardiomyocytes from mouse and human embryonic stem cells and the electrophysiological characterization of these cells. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) have the potential to supply large numbers of cells for cardiac regeneration. Before ESC-CMs can be used for cardiac repair, however, more must be known about their electrophysiology and their ability to functionally incorporate into native cardiac tissue. Our studies show for the first time that ESC-CMs can electrically integrate with neonatal rat ventricular myocytes and by themselves can form an electrophysiologically functional tissue substrate. I currently have my students investigating the influence of mechanical stretch and electrical stimulation on mouse ESC differentiation into cardiomyocytes. We hypothesize that adding these stimuli, and thereby more closely mimicking the in vivo environment, will cause the cells to reach a more fully differentiated state and potentially increase the percentage yield of cardiomyocytes. I also am studying the potential of nanopatterned PEG hydrogels to direct cardiac alignment and thereby influence the cardiac electrophysiology of the resulting tissue. By creating anisotropic structures, our engineered tissue better mimics the native myocardium.

Integrating teaching and research comes naturally to me, and my educational background has prepared me to teach a broad range of courses. As a lecturing professor at Rice University in the Spring of 2005, I used my background to illustrate to my students how the skills they were learning in the tissue culture laboratory course could be applied to do sophisticated research. Currently, I directly supervise two undergraduate student researchers and one graduate student researcher. During my daily interactions with my students, I teach them critical thinking skills through directed questioning and convey key concepts to them through ?mini lectures? and by compelling them to read the literature. Previous students that I have mentored have gone on to successful graduate and medical school careers and one is currently pursuing a faculty position.