In situ formed tissue-adhesive carboxymethyl chitosan hydrogels through photoclick chemistry for wound healing

Chitosan-based hydrogels crosslinked through covalent bonds have been extensively researched for their remarkable wound healing properties. However, their practical application has been limited due to the complexity of the preparation process and weak tissue-adhesive strength. In this study, we present a straightforward method for producing tissue-adhesive carboxymethyl chitosan hydrogels consisting of a single component, without the need for an initiator, catalyst, or external crosslinking agent. We synthesized o -nitrobenzyl alcohol-conjugated carboxymethyl chitosan and utilized 365 nm LED light irradiation to self-crosslink the hydrogels through photo-triggered o -nitrobenzyl alcohol and primary amine cyclization. The resulting o -nitrosobenzaldehyde groups not only covalently crosslinked carboxymethyl chitosan chains but also formed robust covalent bonds with the amino groups from the tissue surface, resulting in enhanced adhesion. Furthermore, the hydrogels demonstrated favorable biocompatibility. In vivo studies using a mice full-thickness defect model demonstrated that the hydrogel significantly accelerated wound healing, indicating their potential as a wound repair dressing.