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Oxidized polysaccharide-based hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility and tissue-adhesive property. In this study, we introduce a new type of chitosan-based hydrogel as a tissue sealant, which was prepared by enzymatic mediation from periodate-oxidized chitosan–polyethylene glycol–tyramine. The oxidized chitosan backbone was expected to enhance the interconnection between the hydrogel layer and collagen in the tissues via the Schiff-base reaction. Proton nuclear magnetic resonance spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the oxidized chitosan. The degree of oxidation of the chitosan backbone was around 14% of the glucosamine units by proton nuclear magnetic resonance. The hydrogel was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with live/dead cell assays showed that the oxidized chitosan-based hydrogel was cytobiocompatible. The hydrogel exhibited high tissue adhesion strength on porcine skin models as well as good tissue-adhesive ability and wound healing properties on rabbit skin. These positive results could be promising for the application of oxidized chitosan-based hydrogels as a wound sealant.
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