Engineered platform to generate 3D cardiac tissues for modeling genetic cardiomyopathies
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Studies to gain mechanistic understanding of heart dysfunction based on animal and traditional cell culture models have significant limitations. Animal models are low throughput and fail to recapitulate many aspects of human cardiac biology, and 2D culture models utilizing human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) are higher throughput but fail to incorporate one or more in vivo parameters, such as 3D architecture, electrical pacing and mechanical constraint. High throughput 3D tissue platforms could better recapitulate the in vivo microenvironment of cardiac tissue. Previous work from our group demonstrated an approach to build 3D cardiac microtissues based on photolithography-based fabrication of a MEMS device, but design limitations prevented further iterations. In this work, we used a 3D printing approach to engineer iPSC-CM-derived cardiac microtissues with different form factors. Microtissues generated in this platform increased in lifespan compared to the first-generation platform by more than 100%. When modeling mutations associated with genetic cardiomyopathy, functional and structural differences were observed between tissues composed of wild-type and mutant iPSC-CMs. These findings suggest that this micro-device platform can be potentially used for both mechanistic and drug discovery studies.