Date of Award
Master of Science (MS)
Hypertrophic Cardiomyopathy (HCM) is the most common inherited cardiovascular disease, where environmental forces and genetic mutations have been heavily linked to heart failure or sudden cardiac death in young people. However, how genetic mutations and environmental forces contribute to HCM phenotype are not well defined. To study the mechanisms and investigate the potential treatments of this disease, it is important to build a model to simulate mechanical loading and recreate micro-environment of cardiomyocytes. In vivo, surgical maneuvers like transaortic constriction allow the study of overload, but these approaches are low throughput and it is difficult to precisely control overload. In vitro models for mechanical overload have shown differences in results. In this study, I contributed to the development of an “overload enhanced iPSC-micro heart muscle (iPSC-μHM)” model, and optimized substrate preparation to improve quantitative analysis of tissue contractility and calcium handling. I also explored the possibility of using synthetic extracellular matrix on optimization of μHM model. Gelatin methacryloyl (GelMA), one of the most common photo-crosslinkable hydrogels, is applied to encapsulate cells. Results show successful reduction of autofluorescence during process of surface modification on substrates. Moreover, I showed the feasibility of cell encapsulated in GelMA, which can potentially reduce the number of cells required to form iPSC-μHM, and to simulate different stiffnesses of micro tissue by varying concentrations of GelMA and photo-initiators.
Nathaniel Huebsch Alexandra Rutz Jianjun Guan