Developing a New Generation of Antimicrobial and Bioactive Dental Resins

Abstract

Dental caries is prevalent, and secondary caries causes restoration failures. This article reviews recent studies on developing a new generation of bioactive resins with anticaries properties. Extensive effects were made to develop new antimicrobial composites, bonding agents, and other resins containing quaternary ammonium methacrylates to suppress plaque buildup and bacterial acid production. The effects of alkyl chain length and charge density and the antimicrobial mechanisms for chlorhexidine, nano-silver, quaternary ammonium methacrylates, and protein-repellent agents were discussed. Synergistic effects of contact-killing and protein-repellent properties were shown to yield the greatest biofilm-inhibition effects. The combination of antimicrobial, protein-repellent, and calcium phosphate nanoparticle remineralization was suggested to provide maximal anticaries effects. In addition, for use orally, cytotoxicity and biocompatibility were important considerations for the new bioactive materials. Furthermore, rather than kill all bacteria, it would be more desirable to modulate the oral biofilm compositions via bioactive resins to suppress cariogenic/pathogenic species and promote benign species. For widespread clinical use of the new antimicrobial and therapeutic materials, whether they would induce bacterial drug resistance needs to be determined, which requires further study. Nonetheless, the new generation of bioactive anticaries resins with therapeutic and biofilm acid-inhibiting properties has the potential to substantially benefit oral health.

Keywords: anti-caries; antibacterial; composites and adhesives; modulating biofilm compositions; remineralization; therapeutic.

Figure 1.

Effects of alkyl chain length (CL) of quaternary ammonium methacrylates in composite on biofilms: (A) colony-forming units (CFU) of 2-day biofilms on composite; (B) lactic acid production (mean ± SD; n = 6). In each plot, values with dissimilar letters are significantly different (P < 0.05). Note the log scale for the y-axis (A). NACP, nanoparticles of amorphous calcium phosphate. (Adapted from Zhang, Cheng, et al. 2016, with permission.)

Figure 2.

Relationship between 3-dimensional (3D) biofilms and resin charge density. Confocal laser scanning microscopy image of 3D biofilms cultured for 2 d on (A) Scotchbond Multi-Purpose (SBMP; 3M), (B) SBMP + 2.5% dimethylaminohexadecyl methacrylate (DMAHDM), (C) SBMP + 5% DMAHDM, (D) SBMP + 7.5% DMAHDM, (E) SBMP + 10% DMAHDM. The x- and y-axes are parallel to resin surface. The z-axis is perpendicular to resin surface. Live bacteria were stained green. Dead bacteria were stained red. (F) Percentage of live bacteria in 3D biofilm versus resin quaternary amine charge density, which was increased with increasing the percentage of DMAHDM in resin. The top and bottom biofilm surfaces were both plotted (mean ± SD; n = 6). (Adapted from Zhou et al. 2016, with permission.) This figure is available in color online.

Figure 3.

Colony-forming units (CFU) of 2-day biofilms on composites for 4 periodontitis-related species: (A) Porphyromonas gingivalis, (B) Prevotella intermedia, (C) Aggregatibacter actinomycetemcomitans, and (D) Fusobacterium nucleatum (mean ± SD; n = 6). Note the log scale for the y-axis. Bars with dissimilar letters are significantly different (P < 0.05). 3MPC, the composite contained 3% MPC (2-methacryloyloxyethyl phosphorylcholine); 3DMAHDM, the composite contained 3% DMAHDM (dimethylaminohexadecyl methacrylate); EBPM, the resin consisted of ethoxylated bisphenol A dimethacrylate and pyromellitic glycerol dimethacrylate. (Adapted from Wang et al. 2016, with permission.)

Figure 4.

Cytotoxicity and biocompatibility. (A) Representative live/dead images of human gingival fibroblasts in vitro cultured in medium containing monomers. The top titles indicate the monomers; the various monomer concentrations in the culture medium are labeled in the images. Live cells were stained green, and dead cells were stained red. Dimethylaminododecyl methacrylate (DMADDM) had less cell cytotoxicity than bisphenol A glycidyl methacrylate (BisGMA). (B) Composite restorations in rat teeth in vivo at 30 d for control restoration without DMADDM and nanoparticles of amorphous calcium phosphate (NACP) versus DMADDM + NACP group. The star indicates an area with inflammatory cells. Blood vessels are indicated by arrows. Control group had slight inflammatory responses. NACP and DMADDM + NACP showed normal pulp tissue without inflammatory response at 30 d and generated greater tertiary dentin thickness. Values are presented as mean ± SD; n = 6. Values indicated by dissimilar letters are significantly different from each other (P < 0.05). (Adapted from Li, Weir, Fouad, et al. 2013 and Li et al. 2014, with permission.) This figure is available in color online.

Figure 5.

Modulating biofilm compositions via bioactive resin to suppress cariogenic species and promote benign species. (A) The ratio of Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis in biofilms, determined by TaqMan real-time polymerase chain reaction. The percentages on x-axis are for dimethylaminododecyl methacrylate (DMADDM) at 0% (control), 2.5%, and 5%. (B) Fluorescent in situ hybridization images of multispecies biofilms (S. mutans, stained green; S. sanguinis, stained red; S. gordonii, stained blue). (Adapted from Zhang, Wang, et al. 2015, with permission.) This figure is available in color online.

Figure 6.

Bacterial drug resistance to cationic biocides. The minimum inhibitory concentrations (MICs) of chlorhexidine (CHX), cetylpyridinium chloride (CPC) and 12-methacryloyloxydodecyl-pyridinium bromide (MDPB) are plotted for (A) Enterococcus faecalis and (B) Streptococcus mutans. MIC determinations were repeatedly performed from passages of 0 to 10 (P0 to P10). MDPB and CPC caused no resistance for E. faecalis and S. mutans. However, repeated exposure of E. faecalis to CHX induced drug resistance. (Adapted from Kitagawa et al. 2016, with permission.)