ApoEVs Transfer Mitochondrial Component to Modulate Macrophages in Periodontal Regeneration

OBJECTIVE: Macrophages are key players in the host immune response to periodontal pathogens and tissue repair. The aim of this study was to explore the potential of apoptotic cell-derived extracellular vesicles (ApoEVs) in modulating the mitochondrial function of macrophages as a mean to enhance periodontal tissue regeneration. SUBJECTS AND METHODS: ApoEVs were extracted from periodontal ligament stem cells (PDLSCs) and characterized to observe their effects on macrophage function. In vivo experiments, ApoEVs were mixed with hyaluronic acid and injected into the periodontal pockets of rats with periodontitis to observe their impact on periodontal tissue regeneration and the immune microenvironment. Functional assays were conducted to confirm whether ApoEVs contained mitochondrial components and which specific components were transferred to regulate macrophage function. RESULTS: The experimental findings showed that treatment of ApoEVs efficiently restored the homeostasis of macrophage and improved tissue regeneration in a periodontitis rat model. Mechanism investigation demonstrated that the efferocytosis of ApoEVs resulted in the transfer of mitochondrial components from PDLSCs to macrophage. The increased mitochondrial components within macrophages improved mitochondrial function and polarization of macrophages towards the anti-inflammatory M2 phenotype, resulting in the improvement of inflammatory environment in periodontal tissues. CONCLUSION: ApoEVs can transfer mtDNA to enhance mitochondrial function in macrophages, fostering their transition to an anti-inflammatory phenotype. Ultimately, this process improves the immune microenvironment in periodontitis and promotes periodontal tissue regeneration.