Thermosensitive Hydrogel PEG–PLGA–PEG Enhances Engraftment of Muscle-derived Stem Cells and Promotes Healing in Diabetic Wound

Abstract

Regenerating new tissue using cell transplantation has relied on successful cell engraftment in the host; however, cell engraftment into the diabetic skin wound is not as successful as in many other tissues. We used a biodegradable and biocompatible triblock co-polymer poly(ethylene glycol-b-[DL-lactic acid-co-glycolic acid]-b-ethylene glycol) (PEG-PLGA-PEG), which forms a thermosensitive hydrogel, as a wound dressing and scaffold. We found that the thermosensitive hydrogel increased the engraftment of muscle-derived stem cells (MDSCs) by 20- to 30-fold until day 20, when the wound was completely closed in a db/db genetically diabetic mouse model. At day 9, 30% of the transplanted MDSCs were found to remain, and 15% remained at day 20 after transplantation. The increased engraftment resulted in enhanced wound healing, as indicated by the wound closure rate, epithelium migration, and collagen deposition. Using MDSCs stably expressing beta-gal and immunofluorescence, we found that 25% of MDSCs differentiated into fibroblasts, 10% into myofibroblasts, and 10% into endothelial cells. We conclude that using the thermosensitive hydrogel as a scaffold increased the engraftment of MDSCs, which leads to improved diabetic wound healing, possibly by retaining the cells at the wound site for longer.