Rapid 3D Bioprinting of Cardiac Tissue Models
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.