Secondary caries is one of the leading causes of resin-based dental restoration failure. It is initiated at the interface of an existing restoration and the restored tooth surface. It is mainly caused by an imbalance between two processes of mineral loss (demineralization) and mineral gain (remineralization). A plethora of evidence has explored incorporating several bioactive compounds into resin-based materials to prevent bacterial biofilm attachment and the onset of the disease. In this review, the most recent advances in the design of remineralizing compounds and their functionalization to different resin-based materials’ formulations were overviewed. Inorganic compounds, such as nano-sized amorphous calcium phosphate (NACP), calcium fluoride (CaF₂), bioactive glass (BAG), hydroxyapatite (HA), fluorapatite (FA), and boron nitride (BN), displayed promising results concerning remineralization, and direct and indirect impact on biofilm growth. The effects of these compounds varied based on these compounds’ structure, the incorporated amount or percentage, and the intended clinical application. The remineralizing effects were presented as direct effects, such as an increase in the mineral content of the dental tissue, or indirect effects, such as an increase in the pH around the material. In some of the reported investigations, inorganic remineralizing compounds were combined with other bioactive agents, such as quaternary ammonium compounds (QACs), to maximize the remineralization outcomes and the antibacterial action against the cariogenic biofilms. The reviewed literature was mainly based on laboratory studies, highlighting the need to shift more toward testing the performance of these remineralizing compounds in clinical settings.

This project aimed to investigate the anticariogenic effect of four chocolate ingredients (polyphenol, theobromine, cacao, and flavanol) against Streptococcus mutans biofilms grown in vitro. Stored S. mutans (UA 159) was transferred to Brain Heart Infusion (BHI) broth and incubated in aerobic incubator for 24 hours at 37°C in 5% CO₂. Following this, 190 µL of each ingredient concentration (0.78–200 mg/mL) and 10 µL of the culture were added to a 96-well plate and incubated for 24 hours at 37°C in 5% CO₂. Then, biofilms were fixed, stained with crystal violet, and analyzed for formation using a spectrophotometer. Control groups included negative control with only S. mutans and sterility control with BHI media. One-way analysis of variance and Tukey tests analyzed the data. Flavonoid at the 6.25 to 25 mg/mL concentrations reduced the S. mutans biofilms (p < 0.001) by 5- to 33-fold. Meanwhile, 50 mg/mL concentrations and higher completely eradicated biofilm growth. Similarly, cocoa concentrations ranging between 12.5 and 200 mg/mL revealed massive antibiofilm action from a 22-fold reduction at 12.5 mg/mL to complete biofilm eradication at 200 mg/mL. Polyphenol was the only ingredient showing biofilm inhibition at all concentrations ranging from almost 10-fold reduction to complete biofilm eradication, which were all significant (p < 0.001) compared to the control. Regarding theobromine, 3.125 mg/mL of it significantly increased the growth of S. mutans biofilms. At the concentration of 6.25 mg/mL, theobromine significantly (p < 0.001) inhibited the S. mutans biofilms by 3.35-fold. While at the range of 25 to 200 mg/mL, theobromine resulted in a reduction between 11-fold and complete biofilm eradication. The findings suggest that flavonoid, cacao, polyphenol, and theobromine may serve as effective adjuncts in preventing dental caries by inhibiting S. mutans biofilm formation. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. The data supporting this study's findings are available from the corresponding author upon reasonable request. ^* Both authors contribute equally Article published online: 06 May 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India