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A double-blind, randomized, cross-over in situ study compared enamel remineralization by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium (CPP-ACP). Remineralization has been shown to be an effective mechanism of preventing the progression of enamel caries. In the study, the enamel lesions were exposed to dietary intake, and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content and plaque composition were analyzed. The study found that for both the gauze-free and -covered lesions, the greatest amount of remineralization was produced by the CPP-ACP sugar-free gum; followed by the gum without CPP-ACP; and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralization and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralization than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralization model including dietary intake irrespective of whether or not gauze was used to promote plaque formation.