Alginate microspheres-collagen hydrogel, as a novel 3D culture system, enhanced skin wound healing of hUCMSCs in rats model.

While stem cell transplantation has emerged as a promising approach to improving wound healing outcomes, the application of stem cells to date has been limited by the poor survival and retention of these cells once transplanted. The survival, development, and migratory activity of transplanted cells can be improved through the use of three-dimensional (3D) culture systems. Here, a novel alginate microsphere-collage hydrogel (AMS-Col gel) 3D culture system was developed and found to improve human umbilical cord mesenchymal stem cell (hUCMSC) survival, permitting their sustained release so as to promote wound healing. Through hematoxylin and eosin staining and Masson's trichrome staining, the prepared hUCMSCs-AMS-Col gel was found to exhibit wound healing activity. On day 7 following the hUCMSCs-AMS-Col gel treatment of model wounds, improved collagen fiber deposition and re-epithelialization were evident, with complete epithelial regeneration as of day 14 and near-total wound healing was evident as of day 21. This hUCMSCs-AMS-Col gel was also associated with increased VEGF and FGF2 expression. Together, these data indicate that AMS-Col gels are a promising and novel form of 3D cell culture system capable of improving hUCMSC-mediated wound healing, highlighting the potential clinical utility of this regenerative strategy.