Abstract 136: Gel Stiffness-tuned, Nanostructure-templated Alignment and Maturation of Cardiomyocytes For Cardiac Tissue Engineering

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Objective: To investigate how the supramolecular structure and mechanical properties of hydrogels made of chemically-defined peptide amphiphiles (PAs) could influence i) the alignment of cardiomyocytes seeded in them and ii) the functional maturation of the cell construct.

Methods: We generated a series of PAs with different peptide sequences that allowed us to make PA gels with stiffness values ranging three orders of magnitude. The nature of the gelation process provides these gels with same-direction oriented nanofibers along an elongated PA gel. We seeded these PA gels with either HL-1 cardiomyocytes or iPSC-derived cardiomyocytes and cultured them for up to two weeks. We then measured cell survival, proliferation and alignment over time and also the electrophysiological properties of the cell construct as a whole.

Results: We found that cardiomyocytes responded to the alignment of the nanofibers in the gel by aligning to them and that this process can be tuned by changing the stiffness of the PA gel. This in turn influenced the investigated electrophysiological parameters of the cell construct suggesting a functional maturation induced by the PA gel properties.

Conclusions: We believe this study shows for the first time that the nanostructural and mechanical properties of hydrogels can be exploited to influence the maturation of cardiomyocytes/cell construct. This can have important implications for strategies that aim to use ESC- or iPSC-derived cardiomyocytes in tissue engineering, as there is a need for their proper maturation and function.

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