A multi-functional double cross-linked chitosan hydrogel with tunable mechanical and antibacterial properties for skin wound dressing

Chitosan hydrogels with essential antibacterial properties and biocompatibility have great potential in tissue engineering and regeneration medicine. However, pure chitosan hydrogel could be limited by insufficient me-chanical properties. In this work, we designed a multi-functional chitosan hydrogel based on the combination of chitosan methacrylate (CTSMA) and sulfhydrated chitosan (CTSSH), which is cross-linked simultaneously by free-radical polymerization reaction and Thiol-ene reaction. The CTSMA/CTSSH (CMS) hydrogels displayed superior tissue adhesive and mechanical properties when compared to pure CTSMA hydrogel. Additionally, the resulting hydrogels exhibited potent antimicrobial effects against both E. coli and S. aureus. Besides, the CMS hydrogels exhibited good biocompatibility as demonstrated by cytotoxicity and cell proliferation experiments using fibroblasts cells (L929) and adipose-derived stem cells (ADSCs). In vivo experiment, the repairing effect of hydrogels on full-thickness skin defect model in rats was studied. Histological and immunohistochemical staining results showed that CMS hydrogels promoted angiogenesis, dermal repair and epidermal regeneration. Overall, the study highlights the potential of the CMS hydrogels as a promising biomaterial in wound healing applications.