(413c) Advanced Hierarchical Topography for Enhanced Cardiomyocyte Maturation: A Multi-Scale Mechanotransduction Approach

In cardiac tissue engineering, enhancing cardiomyocyte (CM) maturation is crucial for developing effective cardiac repair strategies. Traditional approaches, utilizing single-scale topographies such as grooves, pillars, and fibers, face limitations in effectively maturing CMs. This study introduces a novel hierarchical topography that combines nano-pillars (nPs) on micro-wrinkles (µWs), fabricated through capillary force lithography followed by a wrinkling process. This approach enables the creation of a vast array of topographies for systematic investigation into CM responses. Our results significantly advance the field by demonstrating that CM maturation on hierarchical structures is markedly improved, with cardiac differentiation of H₉C₂ rat cardiomyocytes on these structures being approximately 2.8 and 1.9 times higher than on single-scale µWs and nPs, respectively. The study elucidates the importance of the aspect ratio of nPs and the wavelength of µWs in CM maturation, attributing the observed enhancement to improved focal adhesion and mechanotransduction mediated by the intricate interactions between CMs and the hierarchical topography. The implications of our findings are significant, offering a new direction in cardiac tissue engineering that leverages multi-scale mechanotransduction for CM maturation. This methodologically distinct approach not only contributes to the advancement of cardiac repair techniques but also holds the potential to influence the broader field of tissue engineering by highlighting the importance of topographical cues in cellular maturation and differentiation.