An anisotropic electromagnetic hydrogel promotes cardiomyocyte maturation and post-infarction cardiac repair

Effective therapies for myocardial infarction (MI) are essential in lowering associated mortality rates. While hydrogel-based patch therapy has shown promise in improving post-MI cardiac function; it falls short in terms of mature stimulation and lacks the necessary combination of conductive, mechanical, and anisotropic cues for optimal efficacy. In this study, we developed an anisotropic hydrogel by incorporating polydopamine-reduced graphene oxide-ferric oxide (PDA-rGO-Fe3O4) nanohybrids into gelatin methacrylate (GelMA) hydrogels under a direct current-driven magnetic field. Cardiomyocytes (CMs) cultured on anisotropic hydrogels demonstrated oriented growth and exhibited symmetrical contraction-relaxation behaviors, surpassing the performance of cells cultured on pure GelMA and isotropic ones. Moreover, both external electrical and alternating magnetic field stimulations enhanced sarcomere functionality, gap junction protein expression, and electrophysiological activities in CMs within the anisotropic hydrogel group. In an acute MI rat model, the application of the anisotropic hydrogel patch significantly improved cardiac function, mitigated adverse left ventricular (LV) dilation and remodeling, reduced infarct size, increased LV wall thickness, promoted angiomyogenesis, and preserved the structural and connected features between CMs. Overall, our findings highlight the potential of electromagnetic, conductive, and anisotropic GelMA-based hydrogels as scaffolds for mimicking the natural functional myocardium layer and developing effective cardiac patches.