Effect of Dentin Pretreatment Strategies on Bond Strength to Natural Caries-Affected Dentin: A Systematic Review

Background: This systematic review aimed to evaluate the effect of dentin pretreatment strategies on bond strength to natural caries-affected dentin (NCAD) in permanent human teeth. Methods: A systematic search was conducted in PubMed, Web of Science, and Scopus databases up to April 2026, following PRISMA guidelines. Experimental and quasi-experimental in vitro studies evaluating the bond strength of resin restorations to NCAD after the application of dentin pretreatment strategies prior to adhesive procedures were included. Studies involving modified adhesive systems, artificial caries-affected dentin, or primary teeth were excluded. Risk of bias was assessed using the QUIN tool. Due to methodological heterogeneity, a qualitative synthesis was performed. Results: A total of 1071 studies were identified, of which 9 met the inclusion criteria. Pretreatment strategies were categorized into cross-linking/biomodulation, remineralization, and fluoride-based approaches. Cross-linking strategies, particularly flavonoid-based agents, consistently improved bond strength. Remineralization approaches, including CPP-ACP, demonstrated condition-dependent effects, particularly under aging conditions. Fluoride-based strategies showed more variable outcomes. Most included studies presented moderate risk of bias. Conclusions: Cross-linking/biomodulation strategies demonstrated the most favourable bond strength outcomes to NCAD, while remineralization approaches showed potential benefits under aging conditions. However, the available evidence remains limited and methodologically heterogeneous, indicating the need for further standardized studies.