The cytotoxic and biological effects of silver diamine fluoride on human dental pulp cells: A systematic review and meta-analysis.

INTRODUCTION: Silver diamine fluoride is widely used for non-invasive caries management; however, its biological safety near the dental pulp remains controversial. OBJECTIVE: To systematically evaluate and quantitatively synthesize evidence on the cytotoxic and biological effects of SDF on human dental pulp cells. METHODS: This PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD420251166805) included in vitro and ex vivo studies assessing SDF effects on human dental pulp cells. Searches were conducted in PubMed, Scopus, Cochrane CENTRAL, and Google Scholar without date restrictions. Study selection, data extraction, and quality assessment were performed independently by two reviewers. Cell viability outcomes were pooled using random-effects models. RESULTS: Seven in vitro studies (2022-2024) were included. Qualitative synthesis demonstrated a consistent dose-dependent cytotoxic effect of SDF. Clinically used and high concentrations (≥3.8-38%) caused marked reductions in cell viability. Meta-analysis showed minimal cytotoxicity at very low concentrations (0.00001-0.0005%; pooled effect = 0.99, 95% CI: 0.97-1.00), a significant decline in viability at 0.001-0.005% (pooled effect = 0.73, 95% CI: 0.46-0.93), and severe toxicity at concentrations ≥0.008% (pooled effect = 0.14, 95% CI: 0.00-0.41). Most studies reported IC50 values at or below 0.001%. CONCLUSION: SDF exhibits strong dose-dependent cytotoxicity, with biological safety restricted to very low concentrations. Direct or near-pulpal application of conventional SDF concentrations may pose a risk of pulpal toxicity and should be approached cautiously. CLINICAL SIGNIFICANCE: Direct or near-pulpal application of standard SDF concentrations should be avoided. Clinicians should exercise caution in deep carious lesions.