Multifunctional injectable chitosan-based adhesive enhanced by limited oxidation for assisting bone grafting

In clinical, critical bone defects are often treated with molded bone implants, yet they are prone to loosening, shape mismatch with the defect, and infection and inflammation. Herein, we present a limited oxidation strategy of catechol-chitosan (CC) to fabricate an injectable, adhesive, multifunctional nanocomposite hydrogel (OCCL) to assist bone implants in bone defects. Specifically, the oxidative cross-linking of CC within layered nanoclay (LAP) is moderately restricted to avoid excessive oxidation, thereby enhancing its adhesion to the tissue interface. By moderate oxidation of CC and the physical crosslinking boosted by LAP, the OCCL hydrogels show high adhesive strength, underwater adhesion, high antioxidant activity, good biodegradability and excellent antibacterial activity. Taking advantage of these features, the multifunctional OCCL can effectively promote cell growth, cell adhesion, angiogenesis and osteogenesis to facilitate bone regeneration, as demonstrated by <i>in vitro</i> and <i>in vivo</i> analyses. This work presents a promising strategy of limited oxidation to develop injectable and multifunctional adhesives, providing a safe and easy-to-process solution for reliable bone grafts.