Naringenin-Loaded Core–Shell Mg-MOF Nanocomposite Integrated Injectable Hydrogel for Bone Regeneration: Anti-inflammatory, Osteogenic, and Angiogenic

Composite biomaterial systems facilitate regenerative medicine through component synergy. Herein, novel core-shell nanocomposites (N-HMMs) are prepared, with hollow mesoporous silica (HMSNs) as the core and magnesium-gallic acid metal-organic frameworks (Mg-MOFs) as the shell. N-HMMs are loaded with the small-molecule osteoinductive drug naringin (Nar) to form N-HMMs@Nar, which is integrated into methacrylate gelatin/polyethylene glycol diacrylate hydrogels (GelMA/PEGDA, GP) to construct N-HMMs@Nar@GP. N-HMMs@Nar@GP enables sustained release of Nar, bioactive Mg²⁺, and antioxidant gallic acid for synergistic anti-inflammation, osteogenesis, and angiogenesis of bone regeneration. GP adapts N-HMMs@Nar to the traumatic characteristics of bone defects and facilitates <i>in situ</i> treatments. <i>In vitro</i> studies have confirmed the composite materials' biocompatibility, osteoinductive differentiation, and angiogenesis capabilities. The ability of N-HMMs@Nar@GP to enhance osteogenesis and angiogenesis is demonstrated in an <i>in vivo</i> tibial defect model using micro-CT and histopathological analysis. Therefore, N-HMMs@Nar@GP holds significant potential for application in the repair of bone defects.