A dual-functional thermo-responsive hydrogel based on magnesium-Gallate MOFs for enhanced bone regeneration and angiogenesis

The treatment of critical-size bone defect, particularly those with irregular shapes, presents a significant clinical challenge. Chitosan hydrogels, owing to their degradability, excellent biocompatibility and injectability, represent a promising carrier platform for bone tissue engineering (BTE). Bioavailable Mg 2+ serves as a pivotal element in bone regeneration, promoting osteogenesis and angiogenesis to accelerate bone tissue repair. Furthermore, Gallic acid (GA) exhibits anti-inflammatory properties, modulating the immune microenvironment to create favorable conditions for bone regeneration. To control its release behavior, metal-organic frameworks (MOFs) may be constructed by leveraging the coordination interactions between Mg 2+ and GA. This study constructed an injectable thermo-responsive hydrogel using chitosan and sericin as the matrix, functionalizing it by embedding Mg-GA MOF at varying loading capacities. This material system is termed CS-MOF. In vitro experiments confirmed that the Mg-GA MOF-functionalized hydrogel exerts multiple biological functions: promoting osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), inducing angiogenesis in human umbilical vein endothelial cells (HUVECs), and suppressing the inflammatory response of LPS-stimulated RAW264.7 macrophages. Using a rat critical-sized cranial defect model, we demonstrated that the 0.01% wt/vol Mg-GA MOF-functionalized hydrogel significantly enhanced new bone formation and angiogenesis compared to the MOF-free and 0.02% wt/vol MOF-loaded hydrogels. Collectively, this thermo-responsive Mg-GA MOF-functionalized hydrogel represents a promising candidate for clinical translation in bone defect repair.