Nanotechnology strategies for antibacterial and remineralizing composites and adhesives to tackle dental caries

Abstract

Dental caries is the most widespread disease and an economic burden. Nanotechnology is promising to inhibit caries by controlling biofilm acids and enhancing remineralization. Nanoparticles of silver were incorporated into composites/adhesives, along with quaternary ammonium methacrylates (QAMs), to combat biofilms. Nanoparticles of amorphous calcium phosphate (NACP) released calcium/phosphate ions, remineralized tooth-lesions and neutralized acids. By combining nanoparticles of silver/QAM/NACP, a new class of composites and adhesives with antibacterial and remineralization double benefits was developed. Various other nanoparticles including metal and oxide nanoparticles such as ZnO and TiO2, as well as polyethylenimine nanoparticles and their antibacterial capabilities in dental resins were also reviewed. These nanoparticles are promising for incorporation into dental composites/cements/sealants/bases/liners/adhesives. Therefore, nanotechnology has potential to significantly improve restorative and preventive dentistry.

Keywords: amorphous calcium phosphate nanoparticles; dental caries; oral biofilms; quaternary ammonium methacrylate; silver nanoparticles; tooth lesion remineralization.

Figure 1

Representative transmission electron microscopy image of nanoparticles of silver formed in situ in a dental resin matrix. The nanoparticles of silver appeared to be well dispersed in the resin without noticeable agglomerates. The nanoparticle of silver sizes were measured via high-magnification transmission electron microscopy to be 2.7 ± 0.6 nm [35]. Adapted with permission from [38].

Figure 2

Antibacterial activity of dental primer containing nanoparticles of silver and quaternary ammonium dimethacrylate. (A–D) Uncured primer in the agar disk diffusion test: (A) control primer (Scotchbond Multi-Purpose [SBMP], 3M, MN, USA); (B) control primer + 10% QADM; (C) control primer + 0.05% NAg; and (D) control primer + 10% QADM + 0.05% NAg. Note a small inhibition zone for control primer, and much wider inhibition zones for primers with QADM and NAg. (E) Inhibition zone size (mean ± standard deviation; n = 6). (F) Lactic acid production by biofilms cultured for 2 days on various cured resins. Values with dissimilar letters are significantly different from each other (p < 0.05). NAg: Nanoparticles of silver; QADM: Quaternary ammonium dimethacrylate. Adapted with permission from [54].

Figure 3

Killing bacteria inside dentinal tubules in dentin. (A) Dentinal tubules before Streptococcus mutans impregnation, (B) S. mutans impregnation into tubules on the external surface of dentin with the tubules perpendicular to the surface, (C) S. mutans in tubules parallel to the surface on the cross section of dentin by opening the dentin block after bacteria impregnation and (D) higher magnification of the cross section as in (C). 'T' indicates dentinal tubules. Scotchbond Multi-Purpose (SBMP; MN, USA) is a control primer. Arrows indicate S. mutans in tubules. (E) S. mutans CFU in dentin blocks harvested by sonication (mean ± sd; n = 6). The CFU of the bacteria-impregnated dentin without primer was 2.51 × 10⁶ (CFU/dentin block). The other groups had the units of 10⁴ CFU/dentin block. CFU in dentin treated with 10% QADM + 0.1% NAg was three orders of magnitude less than the CFU of control dentin. CFU: Colony-forming units; NAg: Nanoparticles of silver; QADM: Quaternary ammonium dimethacrylate. Adapted with permission from [64].

Figure 3

Killing bacteria inside dentinal tubules in dentin. (A) Dentinal tubules before Streptococcus mutans impregnation, (B) S. mutans impregnation into tubules on the external surface of dentin with the tubules perpendicular to the surface, (C) S. mutans in tubules parallel to the surface on the cross section of dentin by opening the dentin block after bacteria impregnation and (D) higher magnification of the cross section as in (C). 'T' indicates dentinal tubules. Scotchbond Multi-Purpose (SBMP; MN, USA) is a control primer. Arrows indicate S. mutans in tubules. (E) S. mutans CFU in dentin blocks harvested by sonication (mean ± sd; n = 6). The CFU of the bacteria-impregnated dentin without primer was 2.51 × 10⁶ (CFU/dentin block). The other groups had the units of 10⁴ CFU/dentin block. CFU in dentin treated with 10% QADM + 0.1% NAg was three orders of magnitude less than the CFU of control dentin. CFU: Colony-forming units; NAg: Nanoparticles of silver; QADM: Quaternary ammonium dimethacrylate. Adapted with permission from [64].

Figure 4

Durability of dentin bonding agent containing nanoparticles of silver, dimethylaminododecyl methacrylate and nanoparticles of amorphous calcium phosphate. (A) Dentin–adhesive interface showing resin tags ‘T’; (B) higher magnification of a resin tag showing numerous NACPs inside a dentinal tubule; (C) higher magnification showing both NAg and NACP in dentinal tubule and (D) dentin shear bond strength (mean ± SD; n = 10). Values with dissimilar letters are significantly different from each other (p < 0.05). There was a 35% loss in bond strength for commercial bonding agent in 6 months’ water-aging. There was no bond strength loss for antibacterial bonding agents incorporating DMADDM, NAg and NACP. DMADDM: Dimethylaminododecyl methacrylate; NACP: Nanoparticles of amorphous calcium phosphate; NAg: Nanoparticles of silver. Adapted with permission from [68].

Figure 5

SEM images of biofilms grown for 2 days on composites. (A–C) Lower magnification and (D–F) higher magnification. Three composites were tested: CompositeR (Renamel, Cosmedent, IL, USA); CompositeF (Heliomolar, Ivoclar, NY, USA) and composite containing NACP and QADM. For each composite, water-aging for 1–180 days made no difference in biofilm appearance. The images shown here are for composites aged for 180 days, to demonstrate the long-term antibacterial activity of the NACP-QADM nanocomposite. Commercial composites had dense biofilms. NACP-QADM had much less biofilm coverage. In (C & F), ‘R’ indicates the resin composite surface not covered by biofilms. (F) The Streptococcus mutans chains were much shorter on NACP-QADM nanocomposite. d: Days; NACP: Nanoparticles of amorphous calcium phosphate; QADM: Quaternary ammonium dimethacrylate. Adapted with permission from [54].

Figure 6

Remineralization of enamel lesions via nanoparticles of amorphous calcium phosphate nanocomposite. (A & B) NACP made by a spray-drying technique. Arrows in (A) indicate NACP at a lower magnification. At a higher magnification in (B), arrows indicate the small NACP with particle sizes of the order of 10 nm, which adhered together to form a larger particle. (C) Enamel lesion before the 30-day cyclic demineralization/remineralization regimen, and successful remineralization of the lesion after the 30-day regimen. (D) Percentage of remineralization (mean ± standard deviation; n = 6) of human enamel lesions in the 30-day cyclic demineralization/remineralization regimen. These three values are different from each other (p < 0.05). NACP: Nanoparticles of amorphous calcium phosphate. Adapted with permission from [70,72].