Influence of Microscale Patterning and Substrate Stiffness on Cardiomyocyte Maturation

Abstract eng:
Recent advancements in methods of deriving immature human cardiomyocytes from pluripotent stem cells now facilitates the potential of these cells to develop into mature, fillly-fimctional adult cardiomyocytes - the next step towards producing usefill drug screening models. Differentiation protocols are now able to achieve both high yield and purity of stem cell derived cardiomyocytes. However, biochemical signaling alone is insufficient to produce well-aligned, mature cardiomyocytes that recapitulate adult cell functionality. Our work using hESCs explores the use of micropattemed substrates and substrate stiffness to improve the cytoskeletal organization of the immature cardiomyocytes to improve maturation. We show that pattern widths ranging from 30-230ij promote significant increases in nuclear alignment and enhanced myofilament structure due to the feature geometries. Results for immature CMs cultured on patterned PDMS substrates are presented, in comparison to our prior work on glass, showing the portability of this technique between substrates.

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