| dc.description.abstract | Cardiovascular diseases that often result in end-stage heart failure continue to disable and take patient lives around the world. In an effort to provide new therapeutic options for patients waiting for a heart transplant, scientists, clinicians, and engineers are working toward engineering cardiovascular tissue. Three essential components in tissue engineering are the scaffolds, cells, and signals. In this dissertation, I focused on using the decellularized cardiac extracellular matrix as a bioscaffold for creating functional cardiac tissue.
In Chapter 2, we increased cell retention during recellularization using the biomaterial gelatin in the whole decellularized rat heart. Following these recellularization studies of rat cardiomyocytes in rat hearts, we moved toward establishing a model for studying cardiomyocytes in cardiac extracellular matrix under mechanical and electrical stimulation. In Chapter 3, I created cardiac rings by recellularizing rat cardiac extracellular matrix or rat collagen to investigate the effects of the matrix material on cardiomyocyte contractility and cell elongation. In Chapter 4, I moved to a more clinically translatable model of using human induced pluripotent stem cell-derived cardiomyocytes in human pediatric-sized cardiac rings made from decellularized rabbit hearts. These human pediatric-sized cardiac rings were created and characterized for cell viability, distribution, and function. I studied the electrophysiological and structural maturation of cardiomyocytes within these cardiac rings after mechanical stimulation, electrical stimulation, and combined electromechanical stimulation in a bioreactor custom-made for these cardiac rings. Altogether, we showed improved electrophysiological maturation using the combined factors of a dECM bioscaffold with electrical and mechanical stimulation. | |
