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.