1: A conductive silk–MXene/GelMA cardiac patch for promoting stem cell maturation and functional cardiac regeneration

Abstract: Myocardial infarction (MI) results in irreversible loss of cardiomyocytes and the formation of non-conductive scar tissue, disrupting electrical signaling and impairing cardiac function. While stem cell–based therapies offer potential for cardiac repair, their effectiveness is limited by poor survival, low retention, and, importantly, the lack of functional maturation into cardiomyocyte-like cells. Without proper maturation, transplanted cells cannot contribute to synchronized contraction or electrical integration with host tissue. In this work, we developed a conductive and biomimetic cardiac patch composed of electrospun silk fibroin fibers, Ti3C2Tx MXene nanosheets MXene nanosheets, and a gelatin methacryloyl (GelMA) hydrogel. Fiber formation and morphology were characterized by SEM, while FTIR and Raman spectroscopy were used to confirm the chemical composition and structural features of the scaffold This composite scaffold is designed to recreate key aspects of the myocardial microenvironment, including fiber architecture, physiologically relevant stiffness (~10–15 kPa), and enhanced electrical conductivity. MXene incorporation enhances electrical conductivity to support electrophysiological activity, while silk fibroin provides mechanical reinforcement and structural stability to the patch. Beyond structural support, this system is specifically designed to promote stem cell maturation through the integration of multiple cues. Fibers structure guide cell elongation and cytoskeletal organization, while the conductive network enables efficient electrical signal propagation. In addition, controlled electrical stimulation is applied to mimic the rhythmic environment of native myocardium, promoting calcium handling, early sarcomere formation, and improved electrophysiological behavior. These combined cues are expected to enhance cardiomyogenic differentiation and drive functional maturation of human mesenchymal stem cells (hMSCs). Overall, this work provides a platform to study how structural, biochemical, and electrical signals work together to regulate stem cell maturation. By focusing on preconditioning cells toward a more mature and functional cardiac phenotype, this approach aims to improve electrical integration and therapeutic outcomes following myocardial infarction.