A thermally stable bioactive chitosan scaffold with pH-responsive exosome adsorption and release function promotes wound healing

Chitosan is an excellent carrier material for bioactive substances, and its binding ability is affected by the pH value of surrounding environments. Healthy skin is maintained in a slightly acidic environment, whereas the wound healing environment is normally neutral or slightly alkaline. In the present study, the authors proposed developing a thermally stable bioactive chitosan scaffold (T-CS) with pH-responsive exosome adsorption and release functions to promote wound healing. Our results revealed that T-CS could automatically capture exosomes from human umbilical cord mesenchymal stem cells in an acidic environment and release them in alkaline or neutral environments. The exosomes separated by T-CS and the traditional ultracentrifugation (UC) method exhibited similar size and protein markers. Furthermore, the exosomal biological activities of the T-CS (T-CS-E) and UC groups exhibited similar anti-inflammatory, proproliferation, promigration, and proendothelial cell-tube formation effects on human umbilical vein endothelial cells. Similar results were achieved in a mouse model by sustainably releasing exosomes. T-CS-E could facilitate wound healing by enhancing cell proliferation, inhibiting wound inflammation, and promoting vascularization. Therefore, this study developed a T-CS scaffold that integrates exosome isolation and application for wound healing, laying the foundation for future clinical use.