Diagnostic use of extracellular vesicles in dentistry

To review the diagnostic potential of extracellular vesicles (EVs) in dentistry and evaluate the methodological, translatory, and clinical considerations relevant to their use in oral biofluids.

This narrative review synthesizes current evidence on EVs in dental diagnostics, focusing on saliva, gingival crevicular fluid (GCF), and peri-implant crevicular fluid (PICF). The review examines EV nomenclature, specimen sources, pre-analytical handling, isolation and characterization methods, diagnostic benchmarks, and clinical evidence across major oral diseases.

EVs are promising biomarkers because they protect molecular cargo and may enrich disease-relevant signals relative to whole biofluids. Current evidence is strongest for oral squamous cell carcinoma, periodontitis, and peri-implant disease, where EV-associated proteins, RNAs, and microbe-derived signals have shown diagnostic potential. Saliva offers a noninvasive and accessible matrix, whereas GCF and PICF provide greater site specificity for localized disease. However, major barriers remain, including inconsistent nomenclature, co-isolation of non-vesicular particles, variability in sample collection and EV enrichment methods, limited assay standardization, and insufficient multi-site clinical validation.

Oral-fluid EVs represent a compelling but early-stage diagnostic platform in dentistry. Their successful translation will require rigorous methodological standardization, MISEV-aligned reporting, robust analytical and clinical validation, and deployment strategies suited to either point-of-care or centralized laboratory testing.

EV-based assays could support earlier, more objective, and minimally invasive diagnosis and monitoring of oral diseases, particularly periodontal disease, peri-implant disease, and oral cancer, if current technical and translational barriers are overcome.