Exploring The Potential of Extracellular Vesicles from Oral Biofluid as Biomarker for Periodontal and Peri-implant Diseases: Narrative Review

Siti Zakiyah Muharam¹*, Mohd Faizal Hafez Hidayat¹ and Norhayati Liaqat Ali Khan^2,3
1Centre for Periodontology Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia
²Centre of Preclinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia
³Cardiovascular Advancement and Research Excellence Institute (CARE Institute), Universiti Teknologi MARA, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia
*Corresponding Author: Mohd Faizal Hafez Hidayat, Faculty of Dentistry, Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Selangor Branch, 47000, Jalan Hospital, Sungai Buloh, Selangor, Malaysia.

Published: September 02, 2025

DOI: 10.55162/MCMS.09.311

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Abstract  

Background: Current clinical diagnosis of periodontitis and peri-implantitis relies on clinical parameters and radiographic analysis, which are prone to errors and may not consistently diagnose these conditions. Biomarkers, detectable in bodily fluids such as in saliva, gingival crevicular fluid (GCF), or peri-implant crevicular fluid (PICF), offer promising avenues for non-invasive examination of immunological markers for dental disease. EVs possess a remarkable potential as carriers of diagnostic information due to their ability to transport diverse cargoes such as circular RNAs, mRNAs, miRNAs, DNA, lipids, and proteins. Aim: This review aims to identify the most appropriate oral biofluid (GCF, PICF, or saliva) for isolating EVs as diagnostic markers for periodontal and peri-implant diseases, to determine the optimal EV isolation methods and to identify and characterise EV-derived biomarkers in these oral fluids. Methodology: Scopus, Pubmed and Web of Sciences databases were searched for available literature with the keywords; (extracellular vesicles OR exosomes) AND (crevicular fluid OR saliva) AND (periodontitis OR peri-implantitis OR peri-implant diseases) spanning from 2014 to May 2025. Results: A total of eleven articles were found on EVs derived from oral biofluids as biomarkers for periodontal and peri-implant diseases. Crevicular fluids offer site-specificity, enabling direct diagnosis for each tooth or implant. In contrast, saliva is easier and more comfortable to collect but may not provide an accurate reflection of the patient's periodontal condition. Precipitation-based methods are commonly used to isolate EVs, whereas the miRNeasy and Trizol protocols are commonly used for extracting miRNA from EVs. Conclusions: GCF and PICF emerge as the most suitable, site-specific oral biofluids for diagnosing periodontal and peri-implant diseases. A combination of EV isolation methods, such as size-exclusion chromatography (SEC) and precipitation-based techniques, can enhance EV purity. Notably, miRNAs within these EVs represent promising biomarkers for the early and accurate diagnosis of periodontal and peri-implant diseases.

Keywords: extracellular vesicles; exosomes; periodontitis; peri-implantitis; biomarkers; crevicular fluid; saliva

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