UC San Diego

Current drug discovery is impeded by insufficient models that do not accurately recapitulate physiological responses to treatment. Several drugs have recently been taken off the market due to a lack of efficacy or due to unexpected adverse effects, especially cardiovascular, that were not detected during clinical trials. Current models allow cardiomyocytes to self-assemble within cast gels or interact on 2D substrates with limited ability to recapitulate clinical responses to known drugs. In this study, I have utilized a 3D-printing technology named Micro-Continuous Optical Printing (μCOP) that can rapidly and spatially pattern neonatal ventricular mouse cardiomyocytes (NMVCMs) within photocrosslinkable hydrogels. By embedding cardiomyocytes within a designated microarchitecture, cardiomyocytes preferentially aligned with the designed geometry and displayed phenotypic morphology and cytoskeletal alignment. With this 3D-printing system, I designed and printed an asymmetric mechanical testing platform sensitive enough to measure changes in force and calcium transients. I investigated how various complex microarchitectures may affect force production, exhibiting the potential to utilize this system to investigate future disease models. Finally, I adapted this system towards a humanized model, incorporating human embryonic stem cell cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in various platforms for in vitro and in vivo studies. The 3D-printed tissue constructs presented in this dissertation can ultimately be used for future drug discovery, disease modeling, and potentially to restore organ function.