Abstract 332: Nanostructure-Templated Alignment of Cardiomyocytes for 3-Dimensional Cardiac Tissue Engineering

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Introduction: Heart muscle shows a significant amount of alignment and strategies for cardiac tissue engineering should aim at mimicking such topology. So far, conditions to align cardiomyocytes in three-dimensional (3D) engineered cardiac constructs include static and active mechanical stress and the application of a directional electric field. However, the question of how topological cues from the matrix in which cardiomyocytes are embedded affect their alignment has not been addressed yet. Here, we investigated how cardiomyocytes align and mature in novel 3D gels made out of peptide amphiphiles (PAs) that can be aligned at the nanostructure level. Methods: We seeded HL-1 cardiomyocytes, mouse ES cell-derived cardiomyocytes and human iPS cell-derived cardiomyocytes into PA solutions that were either or not aligned upon gellation. We assessed the alignment of the cardiomyocytes along with their maturation status by observing their structural proteins and the formation of functional syncitiums by connexin 43 expression and the propagation of calcium fluxes. We also tested whether the stiffness of the gel affected the above-mentioned parameters by changing the chemical structure of the PAs. Results: We found that cardiomyocytes aligned along the direction of the alignment of the nanostructures in the gel and that the alignment of the matrix contributed to the functional maturation of the construct. Moreover, we observed a relationship between the stiffness of the gels and the alignment of the cardiomyocytes. Conclusions: This study shows for the first time that the nanostructural features of 3D scaffolds can be exploited to create aligned cardiac constructs.