An injectable, self-healing, 3D printable, double network co-enzymatically crosslinked hydrogel using marine poly- and oligo-saccharides for wound healing application

In this study, we designed dual network hydrogels with antioxidant and antibacterial activities using marine poly-and oligosaccharides with skin wound healing potential. The synergy between dual enzymatic co-crosslinking based on glucose oxidize (GOx)/horseradish peroxidase (HRP) and electrostatic interaction be-tween positively charged chitooligosaccharides (COS) and phenolated chitosan with negatively charged phenolated alginate formed a hydrogel. The Gel-COS hydrogels exhibited toughness, self-healing, moldability, injectability, and 3D printability. Investigation of the physicochemical properties of the hydrogels exhibited a swelling ratio (< 50%) and in vitro biodegradation after 9 days. Furthermore, the hydrogels exhibited antioxidant properties and antibacterial activity against E. coli and S. aureus. The hydrogels were not cytotoxic and enhanced the migration of 3D cell encapsulated 3T3-L1 fibroblasts, blood vessel formation, as well as in vivo wound healing in a rat model. The Gel-COS hydrogel can be considered a promising skin wound dressing material.