Dynamic Schiff base linkage-based double-network hydrogels with injectable, self-healing, and pH-responsive properties for bacteria-infected wound healing

The development of wound dressing materials with both self-healing and antibacterial properties for promoting wound closure is highly desirable in health care. Herein, a smart double-network hydrogel (GS/DPPDH) with promising traits was developed by combining a dynamic Schiff base reaction between dialdehyde carboxymethyl cellulose (DCMC) and poly(ethylene imine) (PEI) with free radical polymerization. Because of its abundant amino groups, the common antibacterial drug gentamycin sulfate (GS) can be loaded into hydrogels by the formation of Schiff base bonds with DCMC. The slightly acidic wound microenvironment caused hydrolysis of the Schiff base bonds, thus releasing the drug GS on-demand. The prepared hydrogel not only showed good self-healing and injectable properties but also displayed excellent blood compatibility and cytocompatibility. The in vitro antibacterial experimental data proved that the GS/DPPDH had high antibacterial ratios of nearly 90% against both gram-positive (S. aureus) and gram-negative (E. coli) bacteria. In addition, in vivo assessment in a mouse model of S. aureus-infected full-thickness skin wounds revealed a wound closure ratio of 83.22 +/- 2.90% after 7 days of healing, which was significantly greater than that in the gauze (59.78 +/- 2.60%) and DPPDH (66.08 +/- 0.21%) groups. Taken together, the results showed that the prepared antibacterial double-network hydrogel with injectable, self-healing, and pH-responsive properties exhibits great potential as a dressing material for infected wound healing.