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Purpose: To evaluate the rehardening ability of SDF and its individual components, silver, and fluoride ions, on early enamel caries lesions using artificial saliva with and without mucin., Methods: Early caries lesions were created in human permanent enamel specimens. The specimens (n=36 per group) were then treated with a single application of: SDF (38%), SDF followed by application of potassium iodide (SDF+KI), potassium fluoride (KF); fluoride control, 44,800 ppm (F), silver nitrate (AgNO3); silver control, 253,900 ppm (Ag), or deionized water (DIW). Immediately, the specimens were subjected to 4 days of continuous remineralization with or without mucin (n=18 per subgroup). Changes in Vickers surface microhardness from lesion baseline (ΔVHN) were calculated. Data were analyzed using two-way (intervention vs. rehardening models) ANOVA., Results: In both rehardening models (with or without mucin), SDF (ΔVHN data; mean ± standard deviation; with/without mucin: 26± 19/3± 11) was significantly less effective in rehardening promotion than SDF+KI (37± 12/39± 16) and KF (40± 17/41± 29; P≤ 0.0332). Compared to AgNO3 (9± 9/18± 15) and DIW (3± 7/12± 9), SDF was more effective in the presence of mucin (P≤ 0.001) but not in its absence, similar to DIW (P= 0.1117); less effective vs. AgNO3 (P= 0.0061). The presence of mucin significantly increased the rehardening ability of SDF (P< 0.0001). However, mucin did not affect the extent of rehardening in the other groups (P≥ 0.082). SDF+KI and KF were superior in their ability in rehardening promotion than AgNO3 and DIW in both rehardening models (P< 0.0001). In both rehardening models, ΔL* values from baseline to post-rehardening show that applying KI after SDF significantly lessened the dark staining caused by SDF (P< 0.0001). Under the present in vitro conditions, SDF does not appear to enhance surface rehardening of early enamel caries lesions. The co-presence of mucin during rehardening enhanced the efficacy of SDF which warrants further investigation., Clinical Significance: Silver diamine fluoride + potassium iodide may be a viable option in rehardening of early enamel caries lesions., Competing Interests: The authors declared no potential conflicts of interest. This work was supported by the Indiana University School of Dentistry Department of Cariology, Operative Dentistry and Dental Public Health and by the Oral Health Research Institute Remineralization Research Program. The authors are indebted to Elevate Oral Care LLC, Florida, USA for providing SDF (Advantage Arrest) free of charge., (Copyright©American Journal of Dentistry.)