Hierarchical integration of carbon dot on Ce-MOF nanozymes in a hydrogel for diabetic alveolar bone repair

BA@Ce-MOF exhibits SOD/CAT-like enzyme activities and antioxidant effects. • In situ formation of hydrogel via thiol-ene photo-click chemistry reaction. • The ROS-responsive oxidation of thioether bonds in the hydrogel network accelerates drug release. • Promotes osteogenesis, angiogenesis, and M2 macrophage polarization in vivo. The hyperglycemic and reactive oxygen species (ROS)-rich microenvironment in diabetes readily incites inflammation, and the persistent inflammation exacerbates bone resorption, severely hindering the repair of diabetic alveolar bone defects. The alendronate used in clinical practice can inhibit bone resorption but lacks osteoinductive activity and cannot modulate the inflammatory milieu; traditional Chinese medicine monomers possess anti-inflammatory potential but are limited by low bioavailability. Herein, we developed a multifunctional nanocomposite hydrogel via a hierarchical integration strategy using carbon dots and Ce-MOF nanozymes to promote diabetic alveolar bone repair. In this system, the Ce-MOF, exhibiting superoxide dismutase (SOD)-and catalase (CAT)-like activities, scavenges ROS and enables the sustained release of carbon dots composed of alendronate and baicalin, achieving synergistic antioxidant and antibacterial effects. The hydrogel, formed from vinyl-group-grafted chitosan and thiolated sodium alginate via rapid in situ photoclick chemistry, adapts to irregular defect shapes; the thioether bonds formed in its crosslinked structure enable ROS-triggered acceleration of BA@Ce-MOF nanoparticle release. In vitro, the BA@Ce@CSSA hydrogel demonstrated excellent biocompatibility. Its SOD/CAT activities and the antioxidant function of the monomer synergistically eliminated ROS and induced macrophage M2 polarization for immunomodulation. Concurrently, it enhanced osteogenic differentiation by upregulating RUNX2 and OPN expression. In vivo, Micro-CT and histomorphometric analyses confirmed that BA@Ce@CSSA significantly accelerated and improved the quality of bone regeneration. In summary, this study presents a hierarchically designed therapeutic strategy that effectively promotes bone regeneration by integrating antioxidant, anti-inflammatory, pro-angiogenic, and pro-osteogenic functions within a ROS-responsive hydrogel system, offering a promising approach for treating alveolar bone defects under diabetic conditions.