Cardiovascular tissue regeneration system based on multiscale scaffolds comprising double-layered hydrogels and fibers

We report a technique to reconstruct cardiovascular tissue using multiscale scaffolds incorporating polycaprolactone fibers with double-layered hydrogels comprising fibrin hydrogel surrounded by secondary alginate hydrogel. The scaffolds compartmentalized cells into the core region of cardiac tissue and the peripheral region of blood vessels to construct cardiovascular tissue, which was accomplished by a triple culture system of adipose-derived mesenchymal stem cells (ADSCs) with C2C12 myoblasts on polycaprolactone (PCL) fibers along with human umbilical vein endothelial cells (HUVECs) in fibrin hydrogel. The secondary alginate hydrogel prevented encapsulated cells from migrating outside scaffold and maintained the scaffold structure without distortion after subcutaneous implantation. According to in vitro studies, resultant scaffolds promoted new blood vessel formation as well as cardiomyogenic phenotype expression of ADSCs. Cardiac muscle-specific genes were expressed from stem cells and peripheral blood vessels from HUVECs were also successfully developed in subcutaneously implanted cell-laden multiscale scaffolds. Furthermore, the encapsulated stem cells modulated the immune response of scaffolds by secreting anti-inflammatory cytokines for successful tissue construction. Our study reveals that multiscale scaffolds can be promising for the remodeling and transplantation of cardiovascular tissue.