Research Status of Silver Nanoparticles for Dental Applications

Abstract

Silver nanoparticles (AgNPs) have emerged as a promising antimicrobial agent in dentistry due to their distinctive physicochemical characteristics and broad-spectrum biocidal activity. For example, silver nanoparticles can be incorporated into oral hygiene products in preventive dentistry, composite resins in restorative treatment, irrigation solutions in endodontic treatment, membranes for guided tissue regeneration in periodontal treatment, acrylic resins and porcelains in prosthodontic treatment, coatings in dental implant treatment, and brackets and wires in orthodontic treatment. This paper focuses on summarizing the current knowledge on the antimicrobial use of silver nanoparticles in dentistry, highlighting their antimicrobial mechanism and potential applications in clinical treatment. The literature indicates that silver nanoparticles are a promising antimicrobial agent in dentistry. However, there are still many issues including fundamental antibacterial mechanisms that need to be completely elucidated before clinical applications.

1. Introduction

The human oral cavity is one of the important parts of the body because of its many significant functions and values. The oral cavity harbors many different habitants, including the teeth, gingiva, hard and soft palates, and tongue, which provide warm growth conditions and available nutrients for a number of colonized microbes [1]. The microbes found in the oral cavity have been defined as the oral microbiome, including bacteria, fungi, and viruses [1]. It has been demonstrated that microbial profiles differ significantly according to the oral sites, and the oral microbiome can therefore be seen as a group of site-specific microbial biofilms [2,3]. It is well known that there is a naturally symbiotic relationship between the oral microbe and the host in health. Alterations in the oral environmental conditions (such as temperature, PH, and nutrients) can do harm to the host microbe homoeostasis, hence leading to many infectious disorders including caries, periodontal diseases, pulp infections, peri-implantitis, and denture stomatitis [4]. Furthermore, growing evidence demonstrates that oral diseases play a significant role in the etiopathogenesis of various major chronic systemic conditions, including cardiovascular diseases, cerebrovascular accidents (strokes), rheumatoid arthritis, diabetes mellitus, and respiratory infections such as pneumonia [4]. This established relationship indicates the critical importance of implementing effective preventive measures and therapeutic interventions for oral infections, which could substantially reduce their contribution to the global disease burden [5]. The prevention and treatment of oral diseases remain significant global public health challenges, with mechanical biofilm removal continuing to be the primary and first-line intervention approach. Meanwhile, many systemic antibiotics have been used to meet this challenge because of their potential efficacy, such as penicillin, tetracyclines, metronidazole, and macrolides [6,7,8,9]. However, their widespread and repetitive use may cause subsequent infections due to their resistance or persistence, thus causing them to lose their effectiveness [10,11]. Many other antimicrobial agents have also been gradually developed and researched to target oral pathogens, including chlorhexidine, sodium hypochlorite, fluoride, and antimicrobial peptides (AMPs). However, a number of these studies showed that they failed to achieve expected results due to their drug resistance and some adverse side effects [9,12,13,14]. Collectively, it is essential to develop alternative strategies to treat dental disorders.

The era of nanotechnology has emerged as a prominent field [15]. Nanotechnology is the manipulation of nanometer-sized objects, which are referred to as nanoparticles. It has the potential to bring enormous changes to nano-dentistry. Nanoparticles are nanoscale objects with three external nanoscale dimensions and exhibit characteristics distinct from the corresponding bulk materials. Nanoparticles represent a promising strategy for enhancing oral health owing to their unique physicochemical properties, including ultra-small size and a high surface-to-volume ratio [16,17]. The positive charge plus increased surface area of nanoparticles makes them easier to interface with more negatively charged microbial membranes, and they can be either combined with polymers or coated onto biomaterial surfaces, thereby enhancing their antimicrobial activities [18,19]. Additionally, microorganisms are less likely to acquire resistance on metal nanoparticles than on traditional antibiotics [20]. Such findings interest researchers in the usage of different kinds of nanoparticles, especially silver nanoparticles.

This review focuses on the latest applications of silver nanoparticles in the dental field, including restorative dentistry, root canal therapy, prosthetic dentistry, periodontology, implantology, and orthodontics. In addition, we also discuss the safety issues and problems faced by AgNPs and their possible development directions in the future.

2. Antimicrobial Mechanism of AgNPs Acting on Bacteria

On account of their unique physical, chemical, and biological properties, AgNPs are one of the most commonly used nanoparticles in nanotechnology around the world [21]. They have been applied in diverse fields of dentistry, including restorative dentistry, root canal therapy, orthodontics, prosthetic dentistry, periodontology, and implantology. Because of their greater capacity and higher surface-area-to-volume ratio, silver ions can generate pits and perforations in the cell membrane. AgNPs have gained much attention from scientists and researchers and have shown potent antimicrobial properties [22]. As representatives of inorganic nanoparticles, AgNPs have been demonstrated in numerous studies to highly exhibit a broad spectrum of antimicrobial action on multiple Gram-positive and Gram-negative bacteria, viruses, and fungi, including all kinds of antibiotic strains [23,24,25,26]. Although their antimicrobial mechanism has been extensively investigated, the exact mode of action remains unclear. Currently, many antibacterial actions have been proposed (Figure 1a) [27,28,29]. Its antibacterial actions are mainly owed to the release of silver ions (Ag⁺) [30]. Free silver ions can bind to the plasma membrane and increase membrane permeability, thus causing cell leakage; silver ions can also lead to the denaturation of ribosomes and thus inhibit protein synthesis. After silver ions are uptaken into a cell, the respiratory enzymes can be deactivated, terminating adenosine triphosphate (ATP) production; Ag⁺ can also interrupt the electron transfer chain, hence generating reactive oxygen species (ROS) which can oxidize proteins. Silver ions and ROS can interfere with deoxyribonucleic acid, inhibiting its replication and leading to cell death.

3. Clinical Applications of AgNPs in Dentistry

3.1. Preventive Dentistry

Dental lesions are one of the most common disorders in the world, exerting a strong influence on 95% of the human population in various phases of their lives [32]. Different methods have been used for preventing and treating them; however, their incidence and morbidity rate remains high. With advances in nanotechnology, many studies have evaluated the antimicrobial activity of the agents containing AgNPs against cariogenic microbes, mainly against Streptococcus mutans (S. mutans) and in the prevention of dental biofilm formation, suggesting their potential as effective anticariogenic agents [33,34,35,36,37,38,39]. Thus, numerous in vitro studies [31,40,41,42,43,44,45,46,47] as well as clinical trials [48,49,50,51,52,53,54] have been carried out to evaluate the effectiveness of silver nanoparticles in preventing and arresting early-stage dental caries. A study [31] investigated the remineralization efficacy of sodium fluoride (NaF), nano-hydroxyapatite serum (n-HAP), and nano silver fluoride (NSF) using primary sound anterior teeth. Artificial incipient caries lesions created by immersing the teeth in a demineralizing solution for 72 h, followed by a 10-day pH-cycling regimen. The highest surface microhardness (SMH) values were observed in the NSF group (222.90 ± 28.79), followed sequentially by the NaF group (192.48 ± 30.96), n-HAP group (172.65 ± 21.68), and control group (114.11 ± 20.30), with statistically significant differences between groups (p < 0.05). Atomic force microscopy images showed protective layers in treated groups (Figure 1b–e). A similar study evaluated the remineralization potential of NSF for enamel though optical coherence tomography (OCT), showing that NSF is as efficient as NaF in remineralizing dental enamel [45]. In another study, to assess effectiveness of pre-treatment with NSF on secondary caries at the tooth restoration interface, forty specimens with class V cavities were prepared from 20 human premolar teeth [46]. Then, they were randomly distributed into four groups as follows: glass ionomer cement group (GIC), composite group, NSF pretreatment + GIC, and NSF pretreatment + composite, followed by a pH cycling for 14 days. The mean SMH values at enamel of NSF + GIC (287 ± 34.964) and NSF + composite (246.20 ± 17.82) were higher than GIC (230 ± 32.97) and the composite group (223.20 ± 17.96) (p < 0.05), indicating less demineralization and better surface integrity. The mean outer lesion depth at the interface was also lower in the pretreatment group (p < 0.05), showing better interface restoration integrity. A randomized controlled clinical trial was conducted to prevent untreated caries in the deciduous teeth of children from poor communities, with NSF as the treated group and saline as the control group [52]. At one week, 78% of decayed teeth in the NSF group had arrested caries, while none demonstrated this in control group. At 5 months, the NSF group showed 72.91% with arrested decay, while the control group displayed only 34%. At 12 months, in the experimental group, 65.21% of teeth exhibited arrested caries, while in the control group, only 20.88% of teeth had arrested cavities. In a similar randomized clinical trial, 130 decayed deciduous teeth were included and separated at random into two groups, with NSF as the experimental group and water as the control group [48]. On the seventh day, 81% of teeth in the experimental group displayed arrested decay, whereas none showed this in the control group (p < 0.001); At five months, the experimental group exhibited 72.7%, with 27.4% in the control group (p < 0.001). After 12 months, the NSF group showed 66.7%, while 34.7% was shown in the control group (p = 0.003). A related study demonstrated that the 600 ppm NSF solution exhibited significantly greater efficacy in arresting dental caries (72.7%; p = 0.025) compared to the 400 ppm formulation (56.5%) [54]. To determine demineralization of a pit and fissure sealant incorporating silver nanoparticles, eighty permanent molars without caries were collected in a split-mouth clinical trial [51]. After a six-month follow up, the silver nanoparticle group presented an average microleakage of 33.6%, with 30.6% in the conventional group (p = NS). The reduction in fluorescence found in the silver nanoparticle group was three times higher than the conventional group (p < 0.05), indicating that silver nanoparticles could obviously reduce dental demineralization and likely increase remineralization.

Oral hygiene products, including toothpaste, toothbrushes, and mouthwash, are other important parts of preventive dentistry [55,56,57,58,59,60,61,62]. An in vitro comparative investigation focused on the efficacy of chitosan, AgNPs, and fluorides as antimicrobial ingredients in toothpaste formulations against S. mutans strains through an agar well diffusion array [55]. It showed that AgNPs had the highest efficacy against S. mutans followed by fluoride and chitosan. Another comparative study found that toothpaste containing silver nanoparticles had a better antimicrobial effect than gold nanoparticles; however, its effectiveness is still not as good as traditional toothpaste containing zinc citrate [59]. In 2018, an experimental dentifrice containing NSF was tested in vitro to evaluate its effects on reducing the acidogenecity and adhesion of S. mutans and preventing the demineralization of enamel [56]. All the results demonstrated that the new dentifrice containing NSF had a better antibacterial effect and similar action on enamel demineralization compared to the NaF toothpaste (p < 0.05). Twenty-four healthy people participated in a study to investigate the potential changes in the oral microbiota after toothbrushing with bristles infused with silver nanoparticles or chlorhexidine through the DNA checkerboard hybridization method [60]. After four weeks of toothbrushing, the silver group lowered the total and individual genome counts in both supragingival and subgingival biofilms, while the chlorhexidine group was ineffective in decreasing total counts in the supragingival and subgingival biofilm. But chlorhexidine indeed decreased individual genome counts in supragingival biofilm for the majority of 43 microbial species, including putative periodontal pathogens. Another in vitro study developed an ethanol-free mouthwash containing silver nanoparticles, which could be used for preventing oral infections in immunocompromised patients [61]. Results showed that there was no significant difference in antibacterial effects between ethanol-free mouthwash containing AgNPs and mouthwash containing AgNPs and ethanol (30,000 ug/mL), indicating that silver nanoparticles could be an excellent alternative for ethanol in treating immunocompromised patients.

3.2. Restorative Treatment

Dental caries, a widespread oral disease, adversely affects the health and quality of life of both children and adults [63]. Currently, resin-based composites have gained increasing popularity in dental restorations mainly due to their superior esthetics, good maneuverability, and acceptable biocompatibility [64]. However, these composites are inclined to accumulate more oral microbe and bacterial colonies beside their margins, which may eventually lead to secondary caries [65]. S. mutans are recognized as the main bacteria in cariogenic biofilms responsible for secondary caries [66,67], which are an important factor affecting the life of resin composites. Therefore, to inhibit biofilm formation and prevent microleakage, numerous attempts have been carried out to incorporate antimicrobial agents into composite resins [68,69,70,71,72,73,74,75,76,77,78,79], glass ionomer cement [80], and adhesive systems [81,82,83,84,85,86,87,88,89,90,91,92]. Among them, AgNPs have been extensively investigated as promising antimicrobial agents in dental materials.

In 2010, Banot et al. [69] evaluated the efficacy of AgNP-immobilized halloysite nanotube (HNT/Ag) fillers on the physicochemical and biological properties of a new type of material containing different mass fractions (0, 1, 2.5, 5, 7.5, and 10%). Their findings indicated that the incorporating of 5% HNT/Ag into the resin composite greatly improved mechanical properties, presented satisfactory cure depth and conversion degree, exhibited obvious antibacterial action against S. mutans, and showed no distinct cytotoxicity to NIH3T3 cell lines (Figure 2a–f), evidencing that resin composite containing HNT/Ag has high value in potential dental applications. Similarly, another study (2019) [70] assessed antibacterial and mechanical properties of the new composite resin modified by Ag-doped ZnO nanoparticles. The new material was able to markedly suppress S. mutans on the surface with a slight increase in compressive strength. On account of these results, using Ag/ZnO nanoparticles could be a good choice for developing a novel potential antibacterial resin composite. Various low concentrations of AgNPs were added into the primer of a multi-purpose system; their antibacterial effect, cytotoxicity, and microtensile bond strength were evaluated by Dutra-Correa et al. (2018) [81]. It was observed that the primer containing 250 ppm AgNPs demonstrated excellent antibacterial efficacy and reliable bond strength without cytotoxicity against human dental pulp stem cells. Hence, the addition of AgNPs (250 ppm) seems promising to improve the efficacy of the conventional adhesive system.

The experimental data demonstrated that incorporating AgNPs into composite resins and dental adhesive systems can confer significant antimicrobial efficacy while maintaining their original physicochemical properties, biological performance, and cytocompatibility. These findings suggest that AgNP-modified restorative materials may serve as effective filler components in dental applications, potentially reducing the risk of secondary caries development through their bacteriostatic functionality.

3.3. Endodontic Treatment

Endodontic infections are inflammatory conditions of pulp associated with many various microorganisms. The goal of root canal therapy is to achieve complete eradication of microorganisms from root canal systems through a combination of mechanical and chemical debridement [93,94]. Owing to the anatomical complexity of the root canal system, the power of microorganisms to tolerate harsh environmental conditions and the intrinsic resistance of root canal biofilms, it is a great challenge to completely clean the root canal. Additionally, one of the most common bacteria related to treatment failure is Enterococcus faecalis (E. faecalis) [95]. They are able to survive without nutrients for a long time, infiltrate deeply into dentin tubules, and resist most of the root canal disinfectants and even a few antibiotics. Hence, new disinfection strategies need to be developed. Due to their antibacterial and anti-inflammatory abilities, the incorporation of nanoparticles, especially silver nanoparticles, has gained much attention and interest in the recent years [96,97]. Hou et al. (2020) employed an RNA-sequencing technique to explore the transcriptome variations in E. faecalis treated with silver nanoparticles [97]. This study demonstrated that AgNPs greatly suppressed the growth of E. faecalis by lengthening the lag period in a dose-dependent approach. Moreover, functional analyses of explored genes suggested that the two pathways related to environmental information processing and energy metabolism may be mainly involved in the suppressive effect. Since silver nanoparticles have been shown to have a destructive effect on E. faecalis, they have been evaluated as endodontic irrigants [98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117], intracanal medicaments [101,118,119,120,121,122,123], dental pulp regeneration [124,125], and root-filling materials, including modified gutta-percha [126,127,128,129,130] and incorporated mineral trioxide aggregate (MTA) [131,132,133,134,135,136,137,138].

At present, sodium hypochlorite (NaOCl, 1–5%) is considered as the gold standard for the chemical cleaning of the root canal system in endodontic treatment [98]. Nevertheless, this irrigant is known for its deleterious effects on bond strength and its cytotoxicity to periapical tissues in the case of entering the peri-radicular space [139,140]. Other agents used as irrigant solutions include chlorhexidine (CHX, 2%) and ethylenediamine tetra-acetic (EDTA, 17%) [141,142]. However, both of them have a significantly lower ability to disrupt biofilms compared with sodium hypochlorite. Some studies indicated that silver nanoparticles possessed the same antibacterial effect as NaOCl [99,103,107,114,115,117]. One study demonstrated that a combination of 10-nm silver nanoparticles and 17% EDTA exhibited efficacy equivalent to sodium hypochlorite in eliminating E. faecalis, with no statistically significant difference observed between the two treatments [117]. Additionally, silver nanoparticles exhibited notable efficacy in the removal of the smear layer (Figure 3a–c). Similarly, Abbaszadegan et al. evaluated the cytotoxicity and bactericide activity of silver nanoparticles with different charges, 2.5% NaOCl, and 0.2% CHX, indicating that the positively charged silver nanoparticles were comparable to 2.5% NaOCl against E. faecalis [99]. Furthermore, compared with NaOCl and CHX, those nanoparticles presented a lower cytotoxic effect against L929 fibroblast cell lines. Moghadas et al. (2012) evaluated the antimicrobial effect of a nanosilver particle for the eradication of E. faecalis and Staphylococcus aureus (S. aureus) in comparison to 5.25% NaOCl [114]. These results found this new irrigant was equivalent to 5.25% NaOCl against E. faecalis and S. aureus [114]. However, some other studies showed contradictory results in which silver nanoparticles were not considered as better than sodium hypochlorite [98,101,102,106,112,113,116]. In 2021, Hendi investigated the antibacterial efficacy of a 940 nm diode laser with or without AgNPs against E. faecalis [112].

Among the intracanal medicaments, calcium hydroxide (Ca(OH)₂) is considered as the most commonly used medicament due to its high alkalinity that seems to have an inhibitory effect on most microorganisms [143]. However, its efficacy is not uniform across all endodontic pathogens [143]. Many researchers have suggested that silver nanoparticles as an intracanal medicament could be used as a substitute for calcium hydroxide [101,118,119,120,121]. An in vitro study concluded that the combination of silver nanoparticles with Ca(OH)₂ and CHX was the best for eliminating E. faecalis biofilm [121]. In 2018, Zheng et al. performed a new intracanal disinfection based on lyotropic liquid crystal (LLC) precursor incorporation with 0.5% CHX and 0.02% AgNPs [120]. The precursor formulation demonstrated sustained bactericidal activity against E. faecalis, maintaining a ≥98.5% bacterial inactivation rate for over one month (Figure 3d). Moreover, the CCK8 assay demonstrated that the CHX-AgNPs containing the LLC precursor were safe and nontoxic (Figure 3e). Another study found that 0.02% AgNP gel as a root canal medicament had a stronger bactericidal effect against E. faecalis than calcium hydroxide (p < 0.05) [101]. However, there are also some inconsistent data about the antibacterial effect of AgNPs for root canal disinfection [122,123]. One report showed that calcium hydroxide performed better antimicrobial actions than AgNPs of aloe vera at a concentration of 500, 1000, or 2000 ug against E. faecalis, S. mutans, and Candida albicans (C. albicans) after 48 h incubation (p < 0.001). Another report also found that the antibacterial effect of Ca(OH)₂ was higher than AgNPs of 2 nm alone or in combination with both materials [123]. Gutta-percha with endodontic sealers is the most widely used obturating material. However, gutta-percha has a minor antimicrobial effect. In addition, although root canal sealers exhibit some antibacterial properties, those abilities usually diminish after setting [144]. Thus, many efforts have been made to look for a new antibacterial agent [126,127,128,129,130]. Baras et al. (2019) developed a new endodontic sealant combined with dimethylaminohexadecyl methacry (DMAHDM) and AgNPs [130]. The data demonstrated that the sealer containing 5% DMAHDM and 0.15% AgNPs significantly reduced both dental biofilm formation and viability while maintaining its physical properties. In 2018, Seung et al. concluded that the addition of 2.5% DMAHDM and 0.15% AgNPs into the AH Plus sealer made it more antibacterial against E. faecalis without changing its physical properties when compared with the conventional AH Plus sealer [128]. In contrast to conventional gutta-percha, Mozayeni et al. (2017) demonstrated that nanosilver-coated gutta-percha elicited a heightened inflammatory response when implanted subcutaneously in a rat model [127]. Researchers did not find that the incorporation of silver nanoparticles into the AH Plus sealer could improve its bacterial leakage resistance property [129].

Mineral trioxide aggregate (MTA) has extensive applications in endodontics, such as direct pulp-capping, apexification, repair of furcation and lateral canal perforations, and external/internal root resorption repair [145]. Nevertheless, long solidification time, operational difficulties, and restricted antimicrobial effects have been reported as the drawbacks of MTA [146]. Therefore, it is essential to add antimicrobial agents into MTA to improve its antimicrobial properties. Based on the in vitro study, adding silver nanoparticles to MTA could significantly enhance its antimicrobial efficacy against E. faecalis, C. albicans, and Pseudomonas aeruginosa [137]. Moreover, research has reported that the combination of silver nanoparticles (100 or 200 ppm) with MTA or calcium-enriched mixture (CEM) significantly increased their antibacterial efficacy against all the tested microorganisms (p < 0.05) [132]. Researchers revealed that mixing MTA with 2% zeolite–silver–zinc (Ze-Ag-Zn) had an adverse influence on the compressive strength of MTA, although this incorporation had no cytotoxic effects [136]. Zand et al. found that the incorporation of 1% AgNPs to MTA had a similar inflammatory response in subcutaneous tissue in a rat model when compared with MTA [131]. Additionally, Fernando et al. investigated the impact of AgNPs on the physicochemical and antibacterial natures of white MTA (WMTA) and Portland cement (PC) combined with zirconium oxide (ZrO₂) [138]. The incorporation of AgNPs into WMTA increased the pH and reduced the solubility and setting time. Adding AgNPs into PC/ZrO₂ maintained the pH value, decreased solubility, and improved setting time and compressive strength. After 15 h of contact with an E. faecalis biofilm, WMTA/AgNPs and PC/ZrO₂/AgNPs demonstrated higher levels of bacterial decline.

Collectively, although some contradictory findings have been reported, silver nanoparticles demonstrate significant potential as valuable adjuncts for cleaning of the root canal system in endodontic treatment. However, prior to clinical implementation, further studies are required to completely investigate and confirm antimicrobial, mechanical, physicochemical, and biological properties of silver nanoparticles associated with root canal materials.

3.4. Periodontal Treatment

Peridontitis, provoked by various types of microorganisms, is a prevalent global chronic inflammatory disease that can trigger the progressive failure of periodontal tissues, thereby forming a deep periodontal pocket and gingival recession. The most important pathogens associated with periodontitis are Aggregatibacter actinomycetemcomitans (A. actinomycetem), Porphyromonas gingivalis (P. gingivalis), and Fusobacterium nucleatum (F. nucleatum) [147]. Guided tissue regeneration (GTR), one of the successful clinical therapies for repairing periodontal defects, uses a barrier membrane to inhibit epithelial downgrowth and fibroblast transgrowth into a wound space, thus keeping space for periodontal tissue regeneration [148]. However, bacterial contamination of the wound site is known to markedly compromise the desired results. Thus, some reports with silver nanoparticles as potential antimicrobial agents against periodontal microorganisms have been developed [149,150,151,152,153]. An in vitro study investigated the colonization and penetration of four microorganisms on AgNP-impregnated GTR membranes [151], including S. mutans, A. actinomycetem, F. nucleatum, and P. gingivalis. In this study, three types of GTR membranes were evaluated, including a plain GTR membrane serving as the negative control (GTR-C), (2) a silver nanoparticle-incorporated GTR membrane as the experimental group (GTR-NS), and a doxycycline hydrochloride-loaded GTR membrane as the positive control (GTR-DOX). Results showed that silver nanoparticles were comparative with doxycycline in controlling bacterial adherence across all four organisms, but they were as effective as doxycycline in preventing penetration into the GTR membrane only for A. actinomycetem and P. gingivalis. Craciunescu et al. (2018) biosynthesized stable AgNPs combined with nondenatured type I collagen [152]. The results showed that AgNPs prepared in collagen gel enhanced physiochemical and biological characters, such as spherical morphology, small size (30 nm), positively charged surface, high biocompatibility with human gingival fibroblasts, a wide scope of concentrations, and better antimicrobial activity than AgNPs in citrate, indicating a greater treatment potential in periodontal disease therapy. In 2019, another similar study developed a new AgNP-modified/collagen I-coated electrospun PLGA/PCL scaffold with uncompromising physico-mechanical abilities, excellent biocompatibility, sustained antibacterial effects, and enhanced osteogenic characters, indicating their treatment potential for oral and craniofacial GTR and bone regeneration (GBR) [150]. However, an Indonesian study demonstrated that the periodontal dressing containing silver nanoparticles could provoke foreign body reaction and increase inflammation in rats by ^99mTc-ciprofloxacin [154].

3.5. Prosthodontic Treatment

Denture stomatitis characterized by red focal areas is an inflammatory condition of the denture-bearing mucosa, influencing 50–70% of complete denture wearers. Its etiology is multifactorial and C. albicans is the most important etiologic agent. Denture stomatitis poses a significant clinical challenge in the field of dentistry, and silver nanoparticles as antibacterial agents can be mixed into acrylic resins [77,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172], tissue conditioners [173,174,175], impression materials [176,177], dental cements [178,179], facial prostheses [180,181], and even porcelain for crowns and bridges [182,183,184,185,186].

In 2016, the authors conducted a study to evaluate the flexural strength, impact strength, elastic modulus, and glass transition temperature (Tg) of two types of acrylic denture base resins: heat-polymerized and microwave-polymerized [162]. The incorporation of 0.8% and 1.6% AgNPs significantly reduced the flexural strength and elastic modulus of the microwave-polymerized resin, whereas their addition had little effect on the impact strength of both resin groups. Moreover, the incorporation of AgNPs decreased Tg in both denture base resins. In their study, Li et al. (2016) found that denture base resin containing 5% AgNPs exhibited an inhibitory influence on C. albicans adhesion. The average thickness and the living cell percentage of biofilm that formed on the resin specimens sequentially declined with the increase in AgNP solution concentration [161]. Sun et al. carried out an animal study (2021) in which AgNP solution (NS) was incorporated into acrylic acid and then into methyl methacrylate (MMA) and poly methyl methacrylate (PMMA) in order to prepare the NS/PMMA denture base [155]. Those data indicated that the NS/PMMA group exhibited better esthetic performance and higher antimicrobial properties against C. albicans, E. coli, and S. mutans. Meanwhile, the NS/PMMA material displayed excellent anti-aging properties and exceptional biocompatibility, with little cytotoxicity to L929 cells. A similar study by Bacali et al. in 2020 demonstrated that the PMMA resin loaded with graphene–Ag nanoparticles inhibited the bacterial growth of S. aureus, S. mutans, and E. coli in a dose-dependent manner, with minimal toxicity to human cells as well as improved flexural properties [158]. In another study (2012), compared to an unmodified group, a significantly reduced CFU of the C. albicans strain was found at the modified denture acrylic combined with AgNPs at 20% and 30% [168]. In addition, considering the minimal inhibitory concentration was 3.0 mg/L, Ag⁺ elution contributed little to the antifungal activity in this study (maximum 0.356 ± 0.11 mg/L). However, the poor color stability still required improvement. In a study by Nam et al. (2011), the combination of 0.1% AgNPs and tissue conditioner presented the least significant bacterial effect against S. aureus and S. mutans, and the bacterial effect on C. albicans was 0.5% [174]. There was no statistical difference between 24 h and 72 h incubation times in terms of the microbial inhibitory effect. In their study, Ginjupalli et al. indicated that the addition of silver nanoparticles into irreversible hydrocolloid impression materials produced excellent antimicrobial activity without adverse effects on physical properties (such as gel strength, permanent deformation, flow, and gel time) [176]. Meran et al. (2018) investigated the biocompatibility and antifungal behaviors of silicone facial protheses coated with silver nanoparticles in vitro [180]. Data showed that the AgNP coating was effective against the growth of C. albicans measured by ethanol production by the yeast without damaging human fibroblasts (Hs68). Uno et al. in Japan modified Noritake Super porcelain with the addition of different concentrations of AgNPs (100, 200, 500, and 1000 ppm) [186]. Results indicated that the incorporation of AgNPs significantly increased the fracture toughness and Vickers hardness of porcelain. However, the higher concentrations (500 and 1000 ppm) could cause a color change. Hashem et al. conducted a similar study and concluded that the addition of silver nanoparticles could improve the fracture strength of dental ceramic with an adverse color change [185]. Fujieda et al. used a post-indentation method to investigate the effect of AgNPs on subcritical crack growth (SCG) behaviors of porcelain [182]. Data showed that the incorporation of silver nanoparticles enhanced the fatigue parameter n, which characterized the SCG behavior and indicated that fatigue life would be extended.

3.6. Dental Implant Treatment

Titanium (Ti) implants are widely used to replace missing teeth in dentistry. Unfortunately, the infections associated with Ti implants, including peri-implant mucositis and peri-implantitis, can cause implant breakdown and additional surgical interventions [187]. In order to address these infections, AgNP coatings have been developed and proven to effectively endow implants with inherent antibacterial properties [188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219].

Qiang et al. (2021) fabricated Ti surfaces functionalized with catechol moiety-containing silk sericin (SSC) and AgNPs [206]. As shown in the growth curve, inhibition zone, live/dead staining assay, and quantitative measurement, the AgNP/SSC-coated Ti surface significantly prevented the adhesion of S. aureus and E. coli, as well as early formation of the biofilm (Figure 4a–c). Additionally, the cell toxicity of the c-SSC-Ag surface to L929 mouse fibroblasts was negligible (Figure 4d). Ye et al. (2022) designed a hybrid nanocoating composed of silver nanoparticles decorated with antimicrobial peptides (AMPs) and GL13K was used in this study (Figure 5a) [212]. The results demonstrated that following a 6-h incubation period, the hybrid AgNP-dGL13K coating displayed the strongest antimicrobial efficacy against methicillin-resistant S. aureus (MRSA) and P. aeruginesa. In addition, a subcutaneous infection model in rats demonstrated that more dead bacteria were found with the hybrid AgNP-dGL13K coatings and a denser neutrophilic infiltration was found around the noncoated etched Ti (eTi) (Figure 5b–e). In a study performed by Zhou et al. (2022), devising AMPs with osteogenic fragments were on the surface of AgNPs, and the silk fibroin (SF) was used to take AgNPs@AMPs which are constructed on Ti implants [215]. The 21-day antibacterial evaluation against S. aureus demonstrated that Ag@AP/SF maintained above 99% inhibitory efficacy against both planktonic and adherent bacteria throughout the testing period. Following 7- and 14-day co-culture periods with bone marrow stem cells (BMSCs), the AgNP/AMP-loaded silk fibroin (SF)-based coatings demonstrated enhanced promotion of BMSC adhesion, proliferation, and osteogenic differentiation, as shown in Figure 6a–j. Furthermore, after 4 and 8 weeks of implantation in a rat model, the Ag@AP/SF coatings not only significantly promoted new bone formation but also enhanced osseointegration at the implant interface (Figure 7a,b). In a related study, Zhou et al. (2017) developed silk fibroin (SF)-based coatings loaded with AgNPs and gentamicin (Gen) on titanium implants using polydopamine (PD)-assisted deposition and a cyclic drying process [216]. The PD-S, PD-S-Ag, and PD-S-Ag/g coatings were gained, respectively, in SF, SF/AgNP, and SF/AgNP/Gen solutions. The cell-bacteria co-culture experiment demonstrated that the PD-S-Ag/g coatings significantly enhanced MC3T3 cell proliferation while effectively inhibiting S. aureus adhesion and growth. Furthermore, AgNP/Gen-contained coatings benefited the osteogenic differentiation of MC3T3 cells, such as the production of alkaline phosphatase, secretion of collagen, and calcification. In a split-mouth randomized clinical trial by Odatsu et al. (2020), the AgNP coating applied to the healing abutments was prepared with microwave-assisted synthesis [204]. These data showed that the nano-Ag coating strongly suppressed bacterial attachment on the healing abutments without cytotoxicity on human gingival fibroblasts.

3.7. Orthodontic Treatment

White spot lesions (WSLs) represent a well-documented complication associated with fixed orthodontic treatment. The placement of fixed orthodontic devices creates a beneficial environment for the accumulation of microorganisms and formation of dental biofilm. Cariogenic microorganisms, particularly S. mutans and Lactobacilli, have been identified as primary etiological agents. If left untreated, progressive WSLs may evolve into frank caries lesions requiring restorative intervention. AgNPs have been demonstrated as antimicrobial coatings on orthodontic components (such as brackets [220,221,222,223,224,225], wires [226,227,228,229], elastomeric modules [230], micro-implants [231]) and also as antimicrobial agents for orthodontic adhesives [84,232,233,234,235,236,237,238], cements [239,240,241,242], resin-based composite and acrylic resins [243,244,245,246,247,248,249,250,251], and mouthwash [252].

Recent investigations have demonstrated the significant antimicrobial potential of AgNPs in various orthodontic applications. In a 30-day rat model study [221], AgNP-coated orthodontic brackets exhibited markedly reduced Streptococcus mutans colonization (p = 0.015) and decreased smooth surface caries incidence (p = 0.041) compared to conventional brackets. These findings align with earlier surface modification research by Lee et al. (2011), who developed nanocomposite coatings through a layer-by-layer deposition of polydopamine, functionalized poly(3,4-ethylenedioxythiophene), and AgNPs. Their SS-DO-OH-Ag and SS-DO-OH-PC-Ag coatings exhibited potent bactericidal efficacy against both E. coli and S. mutans, while demonstrating minimal cytotoxicity associated with Ag⁺ ion release [227]. The incorporation of AgNPs into orthodontic adhesives has shown dose-dependent antimicrobial effects. Bahador et al. (2020) identified 5% w/v as the minimum effective concentration for a significant inhibition of Streptococcus sanguinis, S. mutans, and Lactobacillus acidophilus in rat models [233]. This concentration optimization was corroborated by Moreira et al., whose AgNP-modified orthodontic adhesive maintained mechanical properties while achieving statistically significant reductions in cariogenic pathogens [241].

4. Future Perspectives and Conclusions

Extensive research highlighted in this review demonstrates that silver nanoparticles exhibit promising antimicrobial properties, positioning them as a versatile therapeutic agent with diverse applications across dental specialties. Their potential utility spans preventive care, restorative procedures, endodontic therapy, periodontal management, implantology, and orthodontic interventions.

Despite considerable progress in this field, several critical aspects remain insufficiently understood and warrant further investigation. Comprehensive studies are imperative to establish optimal parameters for silver nanoparticle (AgNP) integration, including safe dosage thresholds relative to cellular toxicity, ideal concentration ranges, and particle size specifications. Moreover, researchers should prioritize elucidating potential adverse effects associated with incorporating AgNPs into dental materials, particularly regarding chromatic stability and alterations in mechanical properties. The cytotoxic effects of AgNPs have been primarily attributed to free silver ion release, necessitating rigorous toxicological assessments to evaluate potential risks in dental applications. Current research limitations must be acknowledged that most available data originate from in vitro studies, while robust longitudinal evidence from animal models and clinical trials remains conspicuously absent. Furthermore, the fundamental antibacterial mechanisms of AgNPs have not been fully understood, demanding systematic investigations to unravel the precise molecular interactions and pathways involved.

Artificial intelligence (AI) has emerged as a transformative emerging technology for processing multidimensional information with minimal human intervention through advanced deep learning capabilities. The integration of AI with silver nanoparticles (AgNPs) has demonstrated significant potential across diverse biomedical applications, including pesticide molecular analysis within plants, the diagnosis of invasive fungal infections (IFIs), discrimination of volatile organic compounds (VOCs), and characterization of tumor suppressor genes. These interdisciplinary advances suggest substantial opportunities for implementing AI-enhanced AgNP systems in dental applications. We anticipate that the current findings will establish a valuable framework for optimizing AI-driven AgNP technologies in dentistry, potentially paving the way for innovative diagnostic tools, targeted therapeutic approaches, and enhanced biomaterial development within oral healthcare.