Dentin deproteinization strategies are being revisited as adjunctive approaches to reduce technique sensitivity, improve monomer infiltration to mineralized dentin, and enhance the longevity of resin–dentin interfaces. This organized narrative review critically summarizes the chemistry, kinetics, biological considerations, and clinical translatability of agents used for smear-layer deproteinization or post-etching deproteinization. Searches of PubMed/MEDLINE, Scopus, and LILACS up to October 2025 were used to identify evidence on oxidizing irrigants (sodium hypochlorite/hypochlorous acid, calcium hypochlorite, peracetic acid, chlorine dioxide), enzymatic proteolysis treatments (bromelain, papain, trypsin/pepsin, and GAG-targeting enzymes), physical approaches (heat and lasers), and post-oxidizer reducing/antioxidant strategies. Oxidizers provide the fastest and most surface-verified organic removal, but their clinical value is limited by concentration- and time-dependent oxidative carry-over, which interferes with free-radical polymerization. Enzymes offer a more selective route, although their support is driven largely by bond strength and morphological outcomes rather than direct surface-chemical confirmation. Heat remains a proof-of-principle method rather than a clinical option, whereas laser protocols are highly parameter-sensitive. Overall, deproteinization should be interpreted through a combined framework of surface chemistry, adhesive compatibility, aging behavior, biosafety, and chairside feasibility. Current evidence supports cautious, protocol-specific development rather than routine clinical adoption, with priority given to clinically realistic time-dose windows and paired surface/aging outcomes.
Costa et al. (2026) studied this question.