Tannic Acid-Programmed Hydroxyapatite Biomineralization Enables Bilayered Bone-Mimetic Hydrogels for Mandibular Regeneration

The effective restoration of mandibular defects continues to pose a significant clinical challenge. Although biomimetic hydrogels have shown potential in bone tissue engineering, existing approaches fail to simultaneously replicate the hierarchical architecture of native bone and dynamically regulate the osteogenic niche. This study presents a bioinspired hydrogel system engineered through green hydrogen-bond cross-linking integrated with tannic acid-mediated gradient mineralization, achieving precise emulation of cortical–trabecular bone interfaces across multiple scales. The hydrogel demonstrates multifunctional therapeutic capabilities, including targeted recruitment of bone marrow mesenchymal stem cells, synchronized modulation of oxidative stress, transition of M1 macrophages to M2 macrophages, broad-spectrum antimicrobial activity, and potent osteogenic differentiation. Through spatiotemporal control of microenvironmental cues, the construct establishes a self-regulating repair niche that coordinates angiogenesis and osteogenesis. In vivo evaluation utilizing a rat mandibular defect model confirmed the hydrogel’s efficacy in enhancing osseous regeneration and restoring biomechanical competence. This work pioneers a structural-dynamic dual-regulation strategy, advancing translational solutions for complex craniofacial reconstruction.