Polysaccharide-Based Hybrid Self-Healing Hydrogel Supports the Paracrine Response of Mesenchymal Stem Cells

The aim of stem cell therapy is to repair damaged tissues. Some of the challenges facing its success include cell retention and survival at the wound site. While the retention of cells has been addressed by employing scaffolds, the survival of transplanted cells in the repair tissue is however low. It is hypothesized that the observed regeneration is more a result of migration of tissue repairing cells from adjoining tissues in response to paracrine factors secreted by implanted cells than by the implanted cells per se. In this study, we report the synthesis of a self-healing hybrid hydrogel that is injectable. The hybrid hydrogel was developed using the dynamic equilibrium of Schiff base linkage between the aldehyde groups on carboxymethyl cellulose dialdehyde (CMC-D) and amino groups on carboxymethyl chitosan (CMCh). The hydrogel stiffness and kinetics of gelation were observed to be modulated with different molecular weights of chitosan. In vitro studies demonstrated the cytocompatibility, hemocompatibility, and biodegradability of the hydrogel. The chemotactic, proliferative, and wound-healing response of cells to the paracrine factors secreted from the mesenchymal stem cell (MSC)-hydrogel composite confirmed the ability of the hydrogel to support the paracrine response of stem cells. Our results suggest that the synthesized hydrogel-MSC composite could serve as a potential scaffold for studying the in vitro response of cells to the paracrine factors released by the encapsulated cells as well as a cell delivery vehicle for in vivo applications.