Complex bone defects with irregular geometry, interfacial micro-motion and compromised immune microenvironment pose a formidable clinical challenge. Ideal bone repair materials should simultaneously achieve robust interfacial integration and actively regulate the osteoimmunological milieu. Herein, we developed an injectable and photo-curable double-network hydrogel, termed DPG@MA, based on mussel-inspired chemistry and a nanocomposite strategy. The hydrogel features a dynamically cross-linked network formed by a 3,4-dihydroxyphenylalanine (DOPA)-pectin conjugate (DP) and gelatin methacryloyl (GelMA), enabling stable and conformal adhesion to irregular bone defects. Furthermore, the incorporation of alendronate-loaded mesoporous silica nanoparticles (MA) confers the hydrogel with the capacity for sustained co-release of silicon ions and alendronate, effectively steering macrophage polarization from the pro-inflammatory M1 phenotype toward the pro-healing M2 phenotype. This actively reshapes the immune microenvironment into one conducive to bone regeneration. In rat calvarial and tibial defect models, DPG@MA significantly enhanced bone regeneration and osseointegration while mitigating complications, outperforming the clinical standard Novabone®. This study proposes a novel strategy for designing bone repair materials with integrated “interfacial adhesion-immunomodulation-osteogenesis” functionality, offering a promising therapeutic avenue for complex bone defects with challenging healing barriers.
Liang et al. (Sun,) studied this question.