Irisin-Based Nanocomposites for Antioxidant Purpose and the Promotion of Osteogenesis in the Inflammatory Microenvironment

Current clinical periodontitis treatments including surgical treatment and antibacterial treatment might cause excessive immune response in the host and cannot effectively promote the regeneration of periodontal tissue. In this study, we explored irisin serving as a novel biomarker in gingival tissues from periodontitis patients and confirmed its immunoregulatory roles, including its capacity to scavenge reactive oxygen species (ROS) and suppress inflammatory responses, through activation of the P53 and PPAR-γ signaling pathways. Furthermore, we established a bioactive glass nanoparticle compound with irisin (IR-nBG) and evaluated its antioxidant and osteoimmunomodulatory properties in a ROS-rich inflammatory microenvironment. A coculture system of LPS-stimulated RAW264.7 macrophages and human periodontal ligament cells (hPDLCs) was constructed to closely mimic the pathological microenvironment. Results showed that IR-nBG effectively attenuated oxidative stress, preserved cellular homeostasis, and enhanced osteogenic differentiation under inflammatory conditions. To assess the therapeutic potential of IR-nBG in vivo, a ligature placement method was used to establish a periodontitis model, where IR-nBG significantly suppressed periodontal inflammation, reduced alveolar bone loss, and promoted new bone formation at defect sites. These findings demonstrate IR-nBG as a multifunctional and immuno-responsive nanoplatform has the potential for targeted treatment of periodontitis-related bone defects.