Periodontitis and extracellular vesicles: Emerging roles in inflammation, tissue destruction and systemic crosstalk

Abstract

Abstract Background Periodontitis is a chronic inflammatory disease initiated by microbial dysbiosis and dysregulated host immune responses, resulting in progressive destruction of the tooth‐supporting periodontal tissues. Increasing evidence recognises periodontitis as a systemic inflammatory condition associated with metabolic, cardiovascular, immune‐mediated, and neuroinflammatory disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication, facilitating molecular crosstalk between periodontal pathogens, immune cells, and resident periodontal tissues. Objective This review aims to synthesise current evidence on the biogenesis, microbial and cellular sources, and functional roles of EVs in periodontal inflammation, tissue destruction, and systemic inflammatory interactions, while evaluating their emerging diagnostic and therapeutic potential in periodontology. Methods A narrative synthesis of experimental, mechanistic, and translational studies was conducted to examine the role of EVs in periodontal disease. Evidence from studies investigating vesicle‐associated molecular cargo, signalling pathways, and their involvement in local periodontal pathology and systemic inflammatory responses was critically integrated. Key findings Both bacterial‐derived and host‐derived EVs transport diverse bioactive cargo, including lipopolysaccharides, cytokines, proteolytic enzymes, and regulatory nucleic acids. These vesicles modulate inflammatory signalling pathways, contribute to extracellular matrix degradation, influence immune dysregulation, and promote alveolar bone remodelling. Emerging evidence suggests that periodontal EVs may disseminate systemically, contributing to chronic low‐grade inflammation and influencing pathological processes in distant organs. Vesicles detected in saliva, gingival crevicular fluid, and circulation also demonstrate promise as minimally invasive biomarkers for disease detection and monitoring. Conclusion EVs represent key regulators of periodontal pathogenesis and systemic inflammatory crosstalk. Their diagnostic and therapeutic potential offers promising opportunities for precision approaches in periodontology; however, challenges including vesicle heterogeneity, methodological standardisation, and regulatory considerations remain barriers to clinical translation.