UC San Diego

Given the prevalence of cardiovascular disease (CVD) worldwide and in the US, there is a need for mature cardiac models that recapitulate the disease complexity and function of native cardiac tissue. Conventional two-dimensional (2D) human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) differentiations fail to achieve the maturity levels of more intricate three-dimensional (3D) cardiac models. hPSC-CMs often remain immature, electrically isolated, and may not reflect adult biology. Conductive polymers are attractive candidates to facilitate electrical communication between hPSC-CMs, especially at sub-confluent cell densities or diseased cells lacking cell-cell junctions. Here, we investigated how conductive polymers may be used to facilitate electrical communication between hPSC-CMs in both 2D and 3D platforms to create functionally mature cardiomyocytes for disease modeling and potential therapeutics. First, we summarized past, current, and future engineering methods implemented to direct hPSC-CM differentiations to recapitulate the complexity of native cardiac tissue. Next, we developed conductive electrospun fibrous scaffolds and assessed the structural, functional, and transcriptional changes of hPSC-CMs seeded on a 2D network. Lastly, we translated our 2D findings to 3D cardiac spheroid models to investigate how the presence of conductive microfibers may accelerate cardiac spheroid maturation over standard 3D models. Taken together, these data suggest that conductive polymer platforms are supportive of electrical coupling in hPSC-CMs and promote maturation, which may improve our ability to model cardiac diseases and develop targeted therapies.