Ru-Coordinated Cof Nanozymes Mitigate Periodontitis And Bone Resorption

Eliminating pathological ROS overload while preserving stem cell functionality remains a critical challenge in periodontal regeneration. ROS overproduction exacerbates disease progression by amplifying oxidative stress, impairing tissue repair mechanisms, and promoting structural damage. We engineered a ruthenium-coordinated covalent organic framework (Ru@COF) through solvothermal synthesis, where optimized Ru-N coordination enhances both electron transfer efficiency and catalytic stability. Ru@COF was synthesized by solvothermal method, and characterized structurally. Cellular responses under hydrogen peroxide-induced oxidative stress were assessed using hPDLSCs and MC3T3-E1 cells. RNA sequencing analyzed molecular mechanisms. Ligature-induced periodontitis in male Balb/c mice evaluated therapeutic effects via micro-CT, TRAP staining, Masson dyeing, and osteogenic protein immunofluorescence. All animal experiments have been approved by the Ethics Committee. The Ru@COF nanozyme effectively neutralized intracellular ROS, preserving viability and proliferation in hPDLSCs and MC3T3-E1 cells. By stabilizing cytoskeletal architecture and preserving cell-matrix adhesion, Ru@COF enhanced cellular migration capacity while restoring osteogenic differentiation potential. In ligature-induced periodontitis models, Ru@COF treatment significantly reduced osteoclast counts and collagen degradation, demonstrating greater alveolar bone preservation compared to minocycline hydrochloride. Mechanistically, Ru@COF synergistically attenuated inflammatory bone resorption while promoting regeneration via dual modulation of inflammatory pathways and BMP-2/Runx2 activation. The Ru@COF nanozyme exhibits potent ROS scavenging to mitigate oxidative tissue damage while promoting bone regeneration, establishing a dual-action therapeutic platform for periodontal repair.