Abstract
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.
Highlights
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
Before the study on cardiovascular tissue regeneration in vivo, we investigated the regenerative capacity of cells in the multiscale scaffolds in vitro
We expected that the resultant triple culture system would promote stem cell differentiation into cardiac lineages along with peripheral blood vessel formation to construct in vitro cardiovascular tissue as described in GA
Summary
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. A new concept is required for successful cell transplantation systems capable of controlling a large number of stem cell differentiations, organizing peripheral blood vessel formation, and reducing immune response to enhance cardiovascular tissue regeneration. To satisfy these demands, the cell-based cardiovascular tissue repair trials using biomaterials or cell sheet have been reported recently. We developed multiscale scaffolds incorporating a triple culture system of adipose-derived mesenchymal stem cells (ADSCs) with C2C12 myoblasts on PCL fibers along with human umbilical vein endothelial cells (HUVECs) in fibrin hydrogel to develop in vitro engineered cardiovascular tissue as a newly designed tissue transplantation system. Our study provides a novel cell-based therapy and engineered tissue platform for cardiovascular tissue repair
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