Injectable hydrogels can be suitable for any irregular wounds to play an important role in wound healing, which have attracted much attention from researchers. Here, a chitosan-based double alternating injectable hydrogel had been proposed, which aligned with characteristics of wound healing. First of all, carboxymethyl chitosan (CMCS) and oxidized gellant (OGG) were used to fabricate above double-alternating injectable hydrogel skeleton (COG) through Schiff base bond. Then, dipotassium glycyrrhizinate (DPG) and bioactive glass (BG) were loaded respectively into COG, forming COG2-D10 and COG2-B0.5 hydrogel. Various properties of above hydrogels such as rheological behaviors, injectable capability, cytocompatibility, antibacterial and anti-inflammatory activity were systematically investigated. The results indicated that above hydrogel not only had a stable network structure, good toughness, injectability, and excellent adhesive properties, but also exhibited efficient antibacterial, anti-inflammatory, hemostatic, and biocompatible properties. The investigation of in vivo full-thickness skin wound healing showed that compared with COG2-D10 or COG2-B0.5 hydrogel alone, the double-alternating COG2-D10/COG2-B0.5 hydrogel could better enhance the efficacy of drugs, promote cell migration and proliferation, accelerate collagen fiber deposition and neovascularization, and significantly improve wound healing (p < 0.01). Therefore, the double-alternating therapy strategy of hydrogel will provide a new approach for the clinical treatment of skin wound healing.
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