PurposeThe purpose of this study was to evaluate and compare the remineralization potential of phosphorylated chitosan nanoparticles (Pchi) and silver diamine fluoride (SDF) compared to sodium fluoride varnish (NaF) on microhardness of artificial carious lesions in a biomimetic minimally invasive approach that is being regarded as the future of preventive dentistry.MethodsThe sample size included 40 intact extracted maxillary anterior human teeth. Baseline microhardness was recorded using Vickers hardness test and energy-dispersive X-ray spectroscopy (EDX). Artificial caries-like lesions were created on the exposed enamel by suspending all teeth in demineralizing solution for 10 days in a temperature of 37 °C and then the hardness and EDX were remeasured. Samples were then divided into four main groups: Group A (positive control group)n= 10, treated with NaF, Group Bn= 10, treated with SDF, Group Cn= 10, treated with Pchi and Group D (negative control group)n= 10 that received no treatment. After treatment, samples were incubated in artificial saliva solution at 37 °C in for 10 days and then reassessed. Data were then recorded, tabulated, and statistically analyzed using Kruskal–Wallis test and Wilcoxon signed test. Scanning electron microscope (SEM) was used to analyze the morphological changes of enamel surface after treatment.ResultsGroups B and C showed the highest calcium (Ca) and phosphate (P) content as well as hardness values, while group B had the highest percentage of fluoride. SEM revealed a smooth layer of mineral formed on the surface of enamel for both groups.ConclusionPchi and SDF showed the highest increase in enamel microhardness and remineralization potential.Clinical relevanceThe minimally invasive approach for remineralization could be enhanced using SDF and Pchi.