A ZIF90-tungsten-based nanoparticle hydrogel system with antibacterial and antioxidant properties promotes periodontal bone regeneration by modulating the ROS/Plagl1/Wnt pathway.

Periodontitis leads to alveolar bone resorption, driven by persistent periodontal pathogen infection. Such persistent infection creates a unique microenvironment conducive to sustained reactive oxygen species (ROS) production. Therefore, further investigation into approaches that simultaneously combat bacteria and improve the local microenvironment is needed. In the present study, a hydrogel drug delivery system was proposed, which employed an in-situ synthesis strategy of zeolitic imidazole frameworks 90 (ZIF90) encapsulating tungsten (W)-based polyoxometalate nanoparticles (ZIF90-W) to increase the W5+ ratio and confer ATP responsiveness. ZIF90-W was incorporated into phenylboronic acid-modified quaternary ammonium salt chitosan hydrogel (QPT hydrogel), forming QPT@ZIF90-W hydrogel with responsive release properties in the periodontal pocket. Results demonstrated that QPT@ZIF90-W hydrogel exhibited over 90% antibacterial efficacy against periodontal pathogens. Besides, QPT@ZIF90-W significantly promoted osteogenic differentiation of MC3T3-E1 cells after scavenging mitochondrial ROS and total ROS. Mechanistically, the pro-osteogenic effect of QPT@ZIF90-W hydrogel was associated with the significant upregulation of Plagl1, following oxidative stress elimination and subsequent activating the Wnt signaling pathway, according to the transcriptome sequencing results. Concurrently, in vivo experiments demonstrated that QPT@ZIF90-W hydrogel treatment, compared with other groups, reduced inflammatory cell infiltration, upregulated Plagl1 and osteogenesis related proteins, and partially ameliorated alveolar bone resorption. In summary, QPT@ZIF90-W is characterized by synergistic antibacterial effect and ROS scavenging capability. These dual activities reshape the oxidative microenvironment and then activate Plagl1/Wnt pathway to promote osteogenesis, which offer a novel and potential strategy for the precise treatment of periodontitis-induced bone defects.