Bifunctional mesoporous HMUiO-66-NH₂ nanoparticles for bone remodeling and ROS scavenging in periodontitis therapy

Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH₂ were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH₂ NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH₂ NPs in periodontal tissues. Local injection of HMUiO-66-NH₂ effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-β signaling pathways. In conclusion, HMUiO-66-NH₂ exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.