A Dual-Dynamic Crosslinked Polysaccharide-Based Hydrogel Loaded with Exosomes for Promoting Diabetic Wound Healing

Diabetic wounds are often accompanied by severe inflammation, which is unfavorable for vascular growth and wound repair. Therefore, promoting the healing of diabetic wounds is of great significance. In this study, carboxymethyl chitosan (CMCS) was grafted with 4-formylphenylboronic acid (FPBA) and then crosslinked with oxidized sodium alginate (OAlg) to form a dual-dynamic covalent hydrogel (CPOA) based on borate ester bond and Schiff base bonds. Mesenchymal stem cells' exosomes (Exos) were incorporated into the CPOA to construct CPOA@Exos for diabetic wound healing. Owing to the dual-dynamic covalent crosslinking network, the CPOA hydrogel showed good injectability and self-healing ability. In addition, the hydrogel displayed reactive oxygen species (ROS) responsive properties, enabling both scavenging of multiple free radicals and on-demand release of Exos in the ROS-rich wound microenvironment. A diabetic wound model was established on C57 mice, and treatment with CPOA@Exos demonstrated that it could promote the polarization of macrophages toward the M2 phenotype, enhance cellular proliferation in the wounded area, and thereby accelerate the healing of diabetic wounds. In conclusion, this study provides a new hydrogel wound dressing that can inhibit inflammation for the management of diabetic wounds.