Multidimensional nanofibrous hydrogels integrated triculture system for advanced myocardial regeneration

Myocardial infarction (MI) remains a leading cause of mortality worldwide, posing a significant challenge to healthcare systems. The limited regenerative capacity of cardiac tissue following MI results in chronic cardiac dysfunction, highlighting the urgent need for innovative therapeutic strategies. In this study, we explored the application of a multidimensional nanofibrous hydrogel for myocardial regeneration. We developed a composite hydrogel system by integrating fibrin, polycaprolactone (PCL), and alginate. In this system, fibrin supported cell proliferation and significantly enhanced angiogenesis when combined with human umbilical vein endothelial cells (HUVECs). PCL contributed to the alignment of encapsulated cells, improving their organization within the scaffold. Adipose-derived stem cells (ADSCs) were encapsulated within the hydrogel for their versatile regenerative potential, while C2C12 cells were incorporated for their ability to form muscle tissue. Additionally, the inclusion of alginate not only enhanced the mechanical properties of the hydrogel to better match the biomechanical demands of cardiac tissue but also played a critical role in reducing the immune response, thereby improving the system's biocompatibility. This study presents an advanced platform for myocardial regeneration using a nanofibrous hydrogel system designed to meet the dual requirements of mechanical robustness and cellular compatibility essential for cardiac tissue engineering. The triculture system, consisting of ADSCs, C2C12 cells, and HUVECs, harnesses the regenerative capabilities of each cell type, promoting both angiogenesis and tissue regeneration. This comprehensive approach addresses the immediate needs for cellular survival and integration while effectively overcoming long-term mechanical and immunological challenges.