Emerging Roles of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Therapy of Periodontitis

Periodontitis is a globally prevalent oral disease and is closely associated with various systemic diseases. Periodontitis arises from dynamic and complex interactions between polymicrobial communities and host immune responses. Extracellular vesicles (EVs) are circulating subcellular particles carrying multiple signaling molecules. EVs play a key role in intercellular communication, and hold promise for diagnostic and therapeutic purposes. Bacterial extracellular vesicles (BEVs), released from oral pathogens, have been implicated in delivering virulence factors to host cells. In contrast, host cell-derived EVs (CEVs), secreted by periodontal cells, contain molecular cargo that reflect disease status. Both BEVs and CEVs contribute to periodontitis progression by exacerbating inflammation and tissue destruction, and they may also influence related systemic diseases. Moreover, the molecular components of EVs derived from saliva and gingival crevicular fluid (GCF) show potential as diagnostic biomarkers for periodontitis. In addition, mesenchymal stem cell-derived EVs (MSC-EVs) exhibit therapeutic potential in periodontitis, and engineering approaches have been developed to enhance their therapeutic efficacy and accelerate clinical translation. This review summarizes recent advances in understanding the pathogenic, diagnostic, and therapeutic roles of EVs in periodontitis and discusses current challenges and future directions toward their clinical application.