Lysyl oxidase nanozyme-loaded hydrogel for sustained release and promotion of diabetic bone defect regeneration

The process of regenerating bone injuries in diabetic presents significant challenges because lysine oxidase (LOX), a key catalytic enzyme for collagen cross-linking, is inhibited in hyperglycemia. The supplementation of LOX is constrained by inadequate sources and diminished enzymatic activity, necessitating the development of effective alternatives for enhancing bone regeneration in diabetes. Herein, we reported a lysyl oxidase nanozyme (LON), derived from the catalytic domain of LOX. LON formed a stable coordination structure with the active center Cu²⁺ through histidine imidazolyl nitrogen and quinone oxygen, which is consistent with the conformation of the LOX. Our findings suggested that LON demonstrated the capacity to substitute LOX in promoting collagen synthesis and biomineralization. To enable sustained LON delivery, it was incorporated into a GelMA hydrogel (GH), forming a sustained-release reservoir known as LON-GelMA hydrogel (LONGH). Mechanism of LONGH promoting bone healing to accelerate the crosslinking and maturation stage of collagen were also explored, and the 23 genes closely associated with collagen regeneration and osteogenesis were found to be upregulated. The present investigation outcomes reveal that the engineered LONGH hydrogel presents a novel, simple, and commercially viable approach for bone regeneration, offering significant potential for clinical applications.