Reprogramming the periodontal microenvironment: MOF-hydrogel composites as emerging platforms for periodontitis therapy

Periodontal microenvironment is maintained collaboratively by the oral microbiota, host immune defense, and tissue remodeling. In periodontitis, oral dysbiosis disrupts this physiological equilibrium, precipitating irreversible destruction of periodontal supporting tissues. Current periodontal therapies can only partially modulate the periodontal microenvironment, with limited capacity to promote tissue regeneration. Recently, the synergistic integration of metal-organic frameworks (MOFs) and hydrogels has emerged as a promising nanomedicine strategy for periodontitis therapy. MOFs possess intrinsic antibacterial, osteogenic, and nanozyme activities, along with superior drug delivery capacity; meanwhile, hydrogels offer excellent injectability, high biocompatibility, and robust tissue adhesion, making them ideally suited for localized administration within periodontal pockets. Integrating these dual advantages, MOF-hydrogel composites achieve long-acting antibacterial action, anti-inflammation, immunomodulation, and tissue regeneration following local injection, ultimately reconstructing the periodontal microenvironment. Unlike previous reviews that largely focus on hydrogels or MOFs separately, this review systematically summarizes the fabrication strategies of MOF-hydrogel composites and comprehensively elucidates their latest therapeutic applications and underlying mechanisms in periodontitis. Furthermore, we critically discuss the current challenges associated with clinical translation, including biosafety, large-scale manufacturing, and long-term stability, and provide future perspectives for the rational design and clinical development of next-generation biomaterials for periodontitis therapy.