Inorganic Compounds as Remineralizing Fillers in Dental Restorative Materials: Narrative Review

Abstract

Secondary caries is one of the leading causes of resin-based dental restoration failure. It is initiated at the interface of an existing restoration and the restored tooth surface. It is mainly caused by an imbalance between two processes of mineral loss (demineralization) and mineral gain (remineralization). A plethora of evidence has explored incorporating several bioactive compounds into resin-based materials to prevent bacterial biofilm attachment and the onset of the disease. In this review, the most recent advances in the design of remineralizing compounds and their functionalization to different resin-based materials' formulations were overviewed. Inorganic compounds, such as nano-sized amorphous calcium phosphate (NACP), calcium fluoride (CaF₂), bioactive glass (BAG), hydroxyapatite (HA), fluorapatite (FA), and boron nitride (BN), displayed promising results concerning remineralization, and direct and indirect impact on biofilm growth. The effects of these compounds varied based on these compounds' structure, the incorporated amount or percentage, and the intended clinical application. The remineralizing effects were presented as direct effects, such as an increase in the mineral content of the dental tissue, or indirect effects, such as an increase in the pH around the material. In some of the reported investigations, inorganic remineralizing compounds were combined with other bioactive agents, such as quaternary ammonium compounds (QACs), to maximize the remineralization outcomes and the antibacterial action against the cariogenic biofilms. The reviewed literature was mainly based on laboratory studies, highlighting the need to shift more toward testing the performance of these remineralizing compounds in clinical settings.

Keywords: bioactive; biofilm; dental; resin composite; secondary caries.

Figure 1

Different compounds that were incorporated in different resin-based materials to impart bioactivity and remineralize the surrounding dental tissues subjected to demineralization. (A,B) Scanning electron micrograph showing bioactive glass particles. Reprinted/adapted with permission from Ref. [49]. 2016, © Elsevier. Transmission electron microscope illustrating the size of (C) calcium fluoride (CaF₂) nanoparticles. Reprinted/adapted with permission from Ref. [50]. 2020, Mitwalli et al. Another transmission electron microscope illustrating the size of (D) nano-sized amorphous calcium phosphate (NACP) fillers. Reprinted/adapted with permission from Ref. [51]. 2022, © Elsevier.

Figure 2

The biofilm inhibition of the NACP-DMAHDM against (A) Total microorganisms, (B) Total streptococci, (C) mutans streptococci, and (D) Total lactobacilli. More biofilm inhibition of 4- to 6-log reduction was observed when the DMAHDM was combined with the nano-sized amorphous calcium phosphate (NACP) fillers. Values indicated by different letters are statistically different from each other (p < 0.05). Reprinted/adapted with permission from Ref. [65]. 2020, Balhaddad et al.

Figure 3

(A) The amount of lactic acid produced by multi-species cariogenic biofilms. Higher values indicate more lactic acid production. Values indicated by different letters are statistically different from each other (p < 0.05). (B) The percentage of lactic acid production inhibition shows the capabilities of nano-sized amorphous calcium phosphate (NACP) fillers to prevent demineralization and promote the remineralization process. Reprinted/adapted with permission from ref. [65]. 2020, Balhaddad et al.

Figure 4

Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM-EDX) illustrating the mineral contents of enamel restored with pit and fissure sealant containing nano-sized amorphous calcium phosphate (NACP) fillers. (A) SEM-EDX spectrum highlighting the mineral contents of the enamel surface restored with NACP-containing sealant. (B) Percentage of elemental concentration in weight of calcium, phosphate, and oxygen within the enamel restored with NACP-containing sealant. EDX mapping of elemental (C) calcium and (D) phosphate. (E) EDX mapping shows the overlay of C and D images, where the calcium is indicated in the pink color, and the phosphate is displayed in the green color. Reprinted/adapted with permission from Ref. [72], 2020, © Elsevier.

Figure 5

Polarized light photomicrograph showing dark bands (white arrows) at the enamel surface restored with parental resin-based sealant (A,B) and NAC-containing resin-based sealants (C,D), which represent the demineralized areas. It can be observed that enamel restored with the NAC-containing resin-based sealants is associated with a narrow dark band, compared to the wide one in the control group, suggesting the capabilities of these bioactive resin-based sealants to resist demineralization and mineral loss. Reprinted/adapted with permission from Ref. [72], 2020, © Elsevier.

Figure 6

Scanning electron microscope images showing the growth of cariogenic multi-species saliva-derived biofilms over different bioactive resin-based composites. White arrows are showing the biofilm colonies over the resin-based composites. Combining calcium fluoride nanoparticles and DMAHDM was associated with the least biofilm formation. Reprinted/adapted with permission from Ref. [50]. 2020, Mitwalli et al.

Figure 7

Resin-based dental cement containing 25 wt.% of calcium fluoride (CaF₂) or 12.5 wt.% of CaF₂ and 12.5 wt.% of nano-sized amorphous calcium phosphate (NACP) fillers, releasing high amounts of (A) calcium, (B) phosphate, and (C) fluoride ions. After 80 days of continuous release, the remineralizing resin-based cements were recharged for three consecutive cycles, indicating their capabilities of long-term clinical service inside the oral cavity. Reprinted/adapted with permission from Ref. [104]. 2022, © Elsevier.

Figure 8

Different fluorescence images of six different samples (A–F) showing the capabilities of a resin-based composite containing 15 wt.% of bioactive glass (BAG) to prevent bacterial penetration (red color) and dentin demineralization (green color) by an average of 40%, compared to the control that allowed 100% bacterial penetration. Reprinted/adapted with permission from Ref. [49]. 2016, © Elsevier.

Figure 9

Evaluation of the mineral deposition using Raman analysis after immersion in artificial saliva for different time points. (A) Resin-based sealant showing the scanned surface (500 µm × 500 µm). (B) Phosphate ion (PO₄³⁻) peak at 960 cm⁻¹. (C) As in the legends, color changes from blue to orange indicate more phosphate deposition. More phosphate deposition was observed as more boron nitride nanotubes were incorporated. Reprinted/adapted with permission from Ref. [136]. 2019, Bohns et al.