From constitutive killing to microenvironment-activated antimicrobial activity: a critical narrative review of antimicrobial dental materials for caries prevention

Dental caries remains one of the most prevalent diseases worldwide. It is a biofilm-mediated, diet-modulated, multifactorial, dynamic disease that poses a substantial public health burden. The ecological plaque hypothesis views caries as a consequence of sugar-induced disruption of oral biofilm homeostasis. Accordingly, plaque control is a key element in caries prevention. Conventional restorative treatment repairs damaged structure but does not directly control the underlying biofilm, motivating development of antimicrobial and antifouling dental materials. This critical narrative review examines seven caries-relevant classes: quaternary ammonium compounds (QACs), including quaternary ammonium polyethyleneimine nanoparticles; metallic nanoparticles; photocatalytic titanium-based materials; graphene-based materials; zwitterionic polymers; biomimetic nanozymes; and antimicrobial peptides. Six material-intrinsic classes are compared using two conceptual axes: predominant antimicrobial action (diffusible, contact-dependent, or antifouling) and activation trigger (constitutive, light-induced, or biofilm-microenvironment-responsive). Antimicrobial peptides are considered separately because their activity is encoded by peptide sequence and molecular design rather than an intrinsic material property. Across classes, in vitro antimicrobial, antibiofilm, or antifouling effects are common, but direct evidence of caries prevention is substantially more limited. QACs and metallic nanoparticles have comparatively mature restorative-incorporation evidence; photocatalytic titanium and nanozymes provide triggered catalytic activity; zwitterionic polymers primarily reduce microbial adhesion; graphene remains largely preclinical; and peptide strategies increasingly emphasize pathogen targeting, virulence modulation, and ecological selectivity. Among antimicrobial peptides, C16G2, a specifically targeted antimicrobial peptide directed against Streptococcus mutans, has progressed further clinically, whereas other caries-relevant peptides remain predominantly preclinical. Major translational gaps include inconsistent outcome measures, limited independent replication, incomplete formulation-specific therapeutic-window assessment, and reliance on microbiological rather than disease-level endpoints. Antimicrobial or antibiofilm activity should therefore be interpreted as surrogate evidence unless accompanied by reduced enamel demineralization, lesion development or progression, or caries incidence/arrest. Future studies should prioritize standardized testing, matched efficacy and host-safety assessment, independent validation, and clinically meaningful anticaries endpoints.