We investigated the protective effects of glass ionomer cement (GIC) and surface pre-reacted glass ionomer (S-PRG) fillers used as dental restorative materials on the demineralization of bovine enamel during the incubation in a lactic acid solution with pH = 4.0 conducted for 6 d at a temperature of 37 °C. Scanning electron microscopy images of the specimen surfaces from the group containing only enamel blocks revealed the presence of apparent enamel prism peripheries after 6 d of treatment. The mineral was etched from the enamel surface, and a large number of Ca ions were detected in solution. In contrast, the enamel blocks incubated together with discs of GIC or S-PRG fillers did not exhibit demineralized surfaces, owing to the neutralization of the acid solution by the fillers within the first 3 h of the incubation process. The observed pH neutralization effect was attributed to the release of different ions from the fillers and could be utilized for suppressing the progression of caries.bioactive materials before employing a restorative approach that requires the removal of tooth tissue [7].The main purpose of developing bioactive and antibacterial materials is to prevent damage of hard tissues. Glass ionomer cements (GICs) have been widely used for the conservative treatment of enamel and dentin because of their beneficial properties such as strong chemical bonding to the tooth substrate and release of fluoride ions [8]. Furthermore, while conventional GICs release the ions of their constituent materials, light-cured GICs produce significant amounts of Al, Ca, F, Na, P, Si, and Sr ions in neutral or acidic solutions over time and can effectively neutralize lactic acid solutions [9,10] to prevent demineralization of the areas adjacent to the tooth surface and suppress the formation of initial caries.A few years ago, a new zinc-containing GIC characterized by a higher flexural strength as compared with those of conventional GICs was developed [11]. However, after two years of clinical trials, it was found to be unsuitable for cavity preparation [12]. Meanwhile, surface pre-reacted glass ionomer (S-PRG) fillers were introduced as bioactive materials that were able to retain their basic properties by forming a stable glass ionomer phase on the treated surface through the acid-base reaction between the fluoro-boro-alumino-silicate glass and polyacrylic acid [13]. These fillers represent a novel class of particle materials that can be incorporated into resin matrices to induce the release of different types of ions and thus produce a strong bioactive effect. The results of in-vitro studies demonstrated the effectiveness of such materials in inhibiting the demineralization of the tooth substrate [14][15][16] and preventing the initiation of caries. In addition, an endodontic root canal sealer containing an S-PRG filler (i.e., S-PRG sealer) exhibited good antibacterial and anti-inflammatory properties. Finally, the implantation of S-PRG sealer into the subcutaneous tissues of rats noticeably decreased their inflamma...