Analytical methods for biomarker-based diagnosis of pulpitis in minimally invasive biological fluids: a systematic review.

INTRODUCTION Inflammatory biomarkers measured in minimally invasive biological fluids are promising objective tools for diagnosing pulpitis. However, the analytical methods used to detect and quantify these biomarkers, and their diagnostic performance, have not been critically evaluated. This review aimed to identify and assess the analytical methods for detecting and quantifying inflammatory biomarkers in gingival crevicular fluid, dentinal fluid and pulpal blood to distinguish healthy pulp from different stages of pulpitis.

Methods

This systematic review followed PRISMA 2020 guidelines and was prospectively registered in PROSPERO (CRD420261289672). PubMed/MEDLINE, Embase, Scopus and the Cochrane Library were searched, alongside grey literature. Risk of bias was assessed using QUADAS-3. All included studies informed the synthesis, whereas GRADE assessment was limited to diagnostic questions from studies reporting individual-level discrimination.

Results

Nineteen of 6,508 records were included. Six analytical strategy categories were identified. ELISA was the most frequently used (9 studies), followed by Luminex-based multiplex immunoassays, fluorometric assays, cytometric bead array, other multiplex immunoassays, and label-free LC-MS/MS proteomics. Only 3 of the 19 studies formally evaluated diagnostic discrimination; in these three studies, some individual biomarkers and multimarker models showed high discriminatory performance (AUC 0.90-0.997), but all estimates derived from single, internally validated datasets and no direct comparisons between analytical strategies were performed. Certainty of evidence was low.

Conclusions

No biomarker-based analytical approach currently has sufficient evidence tosupportroutine clinical use. Although some biomarkers appear promising, comparative evidence remains insufficient.