Osteoimmunometabolic modulation via hydrogen-self-supplying magnesium-reinforced collagen membrane for enhanced guided bone regeneration.

Abstract

Localized delivery of molecular hydrogen (H₂) in bone tissue engineering remains largely unexplored, despite its potent antioxidative and anti-inflammatory properties. In this study, we present a multifunctional collagen membrane reinforced with micro-magnesium wires coated with metal-phenolic networks (Col-MMW), designed for guided bone regeneration (GBR). The embedded magnesium wires provide mechanical reinforcement, enhancing the membrane's structural integrity and space-maintaining capability during early healing. Concurrently, magnesium degradation enables sustained, site-specific release of H₂ and magnesium ions (Mg²⁺), offering a synergistic strategy to modulate the osteoimmune environment. Col-MMW attenuates intracellular reactive oxygen species (ROS) and reprograms cellular metabolism from glycolysis toward oxidative phosphorylation, thereby activating the nuclear factor erythroid 2-related factor 2 (NRF-2)-mediated redox balance pathway and suppressing nuclear factor kappa B (NF-κB) pathway-driven inflammation. This osteoimmunometabolic reprogramming leads to a significant reduction in inflammatory responses. In vivo studies, including rat subcutaneous implantation and calvarial defect models, demonstrated that the immunoregulatory effects of Col-MMW significantly promoted osteogenesis. By integrating mechanical reinforcement with localized metabolic and immune modulation, Col-MMW redefines the design paradigm of GBR membranes. These findings highlight Col-MMW as a next-generation biomaterial that combines structural integrity with targeted osteoimmunomodulation, addressing the unmet need for intelligent biomaterials for bone repair.