From constitutive killing to microenvironment-activated antimicrobial activity: a critical narrative review of antimicrobial dental materials for caries prevention
9 affiliations
- 1College of Dentistry, The Ohio State University, Columbus, OH, United States
- 2School of Dentistry, University of Washington, Seattle, WA, United States
- 3Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH, United States
- 4The ADA Forsyth Institute, Somerville, MA, United States
- 5Department of Comprehensive Dentistry, University of Texas at San Antonio School of Dentistry, San Antonio, TX, United States
- 6Department of Restorative Dentistry, School of Dentistry, University of Washington, Seattle, WA, United States
- 7Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, United States
- 8Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, United States
- 9Division of Restorative and Prosthetic Dentistry, College of Dentistry, The Ohio State University, Columbus, OH, United States
Abstract
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.
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BibTeX
@article{xin2026from,
title = {{From constitutive killing to microenvironment-activated antimicrobial activity: a critical narrative review of antimicrobial dental materials for caries prevention}},
author = {Xiwen Xin and Ziying Tang and Yuejia Deng and Yulong Zhang and Hai Zhang and Bennett T. Amaechi and Andre V. Ritter and Alvin G. Wee and Justin Kaspar and Jing Zhao and Andréa Ferreira Zandoná and Xuelian Huang},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1983359},
url = {https://doi.org/10.3389/fcimb.2026.1983359},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From constitutive killing to microenvironment-activated antimicrobial activity: a critical narrative review of antimicrobial dental materials for caries prevention
AU - Xiwen Xin
AU - Ziying Tang
AU - Yuejia Deng
AU - Yulong Zhang
AU - Hai Zhang
AU - Bennett T. Amaechi
AU - Andre V. Ritter
AU - Alvin G. Wee
AU - Justin Kaspar
AU - Jing Zhao
AU - Andréa Ferreira Zandoná
AU - Xuelian Huang
PY - 2026
DA - 2026/10/12
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1983359
UR - https://doi.org/10.3389/fcimb.2026.1983359
AB - 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.
SN - 2235-2988
ER -