Nano silver used in toothpaste helps prevent tooth decay

Two researchers independently performed a literature search for English-language publications using the Embase, Medline, PubMed, and Scopus databases. The keywords nano silver used were (silver nanoparticles or AgNPs or nano silver or nano-silver) and (cavity or remineralization). They screened titles and abstracts to identify potentially eligible publications. They then retrieved the full text of the identified publications to select the original study that reported on silver nanomaterials for tooth decay prevention.
Results: The search identified 376 publications and 66 articles included in this study. The studied silver nanomaterials (SNPs) were classified as resins with silver nanoparticles (n = 31), silver nanoparticles (n = 21), glass ionomer cements with silver nanoparticles (n = 7) and nano silver fluoride (n = 7). Most (59/66.89%) studies investigated antibacterial properties and all found that silver nanomaterials inhibited the adhesion and growth of cariogenic bacteria, mainly Streptococcus mutans..
Although silver nanomaterials were used as an anti-cavity agent, only 11 (11/66, 17%) studies reported the impact of nanomaterials on the mineral content of teeth. Eight of them were laboratory studies, and they found that the silver nanomaterial prevented the demineralization of enamel and dentin under acid-challenged conditions or cariogenic biofilms. The remaining three trials were clinical trials that reported that silver nanomaterials prevent and arrest dental caries in children.
Conclusion: Silver nanoparticles have been used alone or with resins, glass ionomers, or fluoride to prevent tooth decay. SNPs material inhibit the adhesion and growth of pathogenic bacteria. They also interfere with the demineralization of enamel and dentin.

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Introduce
Nanotechnology is the science, engineering and technology concerned with the synthesis, characterization and application of materials by controlling shape and size at the nanoscale. 1 The development of nanomaterials for medical care is an important part of nanotechnology. The European Commission defined “nanomaterials” in 2011 as natural, incidental or manufactured materials containing particles in an unbound state, either as aggregates or agglomerates. For 50% or more particles in the numerical size distribution, one or more of the outer sizes ranges from 1 nm to 100 nm. 2 Nanomaterials may possess unique physical properties, such as uniformity, electrical conductivity or special optical properties, making them desirable in biology and materials science. Because of their large surface area to volume ratio, they exhibit different biomedical activities than normal sized materials. The application of nanomaterials can significantly improve human health and daily life over the past two decades. 4

Among the different types of nanomaterials, metallic nanomaterials – especially silver nanomaterials – have shown great promise for biomedical applications. Silver nanomaterials in medicine enable researchers and clinicians to enhance medical imaging by providing more detailed images of cellular processes. They support medical diagnosis with molecular contrast agents and materials to enable earlier and more accurate initial diagnosis. Silver nanomaterials also improve drug delivery by increasing solubility and thus enhancing bioavailability. They are also used in cancer therapy to kill drug-resistant tumor cells and improve treatment efficacy by low-targeting and delivery of these anti-cancer drugs to tumor tissues..số 8

SNPs materials also attract public attention because of their exceptional antibacterial activity with low toxicity and low cost. They are used in low concentrations and do not induce bacterial resistance. Different antibacterial activities of silver nanomaterials have been proposed although the exact mechanism of the antibacterial effect of silver nanomaterials has not been fully elucidated. SNPs release silver ions that penetrate the microbial membrane and disrupt deoxyribonucleic acid transcription and protein synthesis. In addition, silver ions can inactivate respiratory enzymes and eventually cause cell lysis. Silver nanoparticles from nanomaterials can accumulate in the pores of the cell wall and cause membrane denaturation. They are also capable of penetrating bacterial cell walls and cytoplasmic membranes, causing denaturation of cell walls and cytoplasmic membranes. 11

Researchers investigated the use of silver nanomaterials in dental materials as an antimicrobial agent for clinical care. For example, silver nanoparticle modified implants have been developed to prevent infection around the implant. Many studies have investigated SNPs material for the prevention of dental caries. Silver nanoparticles are incorporated into orthodontic adhesives and brackets to prevent tooth decay, which is a common complication of orthodontic treatment. Silver nanoparticles can also be added to restorative materials to prevent secondary caries, which is a common cause of unsuccessful restorations.. 14 The application of silver nanomaterials to combat tooth decay, including inhibiting biofilm formation and correcting the balance of demineralization and remineralization, is a promising avenue for prevention and treatment. Caries. However, a search found rare reviews of silver nanomaterials for preventing tooth decay. Therefore, the aim of this study was to perform a systematic review of the use of silver nanomaterials for the prevention of dental caries.

Materials and methods for finding information about nano silver

Search strategy

Two independent investigators (Yin and Zhao) performed literature searches to identify publications using four commonly used databases: Embase, Medline, PubMed, and Scopus. The search is limited to publications in English. They searched the publications using the keywords ((silver nanoparticles) OR (AgNPs) OR (silver nanoparticle) OR (silver nanoparticle)) AND ((cavities) OR (cavities)). No publication year limit has been set and the last search was made on February 29, 2020 ( Image 1 ).

Graph of searching for nano silver documents Graph of searching for nano silver documents Biểu đồ tìm kiếm tài liệu nano bạc Chart nanosilver document search Tìm kiếm tài liệu nano trên biểu đồ

Research selection and data extraction

Two investigators independently checked and excluded duplicate publications from four databases to generate a list of publications. They sifted through the titles and abstracts of the publications to identify a list of potentially eligible articles. They excluded literature reviews, case reports, conference papers, publications on non-nanoscale silver compounds and studies unrelated to caries and abstracts without papers. full. The two investigators took the full text of the remaining publications for review. They selected publications investigating the use of silver nanomaterials in the prevention of tooth decay, including the use of silver nanomaterials to inhibit the growth of pathogenic bacteria and demineralize hard tissue. tooth. Two investigators performed manual screening of the reference lists of selected publications. They then discussed the inclusion of selected publications with another investigator (Chu) to reach agreement on the list of publications to be included in this study.
For included publications, the following information is recorded: publication details (author and year), nanomaterials studied, methods, results of assessments, and other key findings.

Results

An initial literature search found 376 potentially eligible publications (95 articles in PubMed, 67 articles in Embase, 132 articles in Scopus, 82 articles in Medline). A total of 132 duplicate records of publications were removed ( Image 1). Another 164 publications were removed after screening titles and abstracts because these 164 were literature reviews, studies on other silver compounds, non-cavity related studies, and other studies. Other unrelated rescues. Full text was collected for the remaining 80 publications. A manual search of the references of these 80 selected publications did not identify any additional publications that met the inclusion criteria. Fourteen publications were excluded because they did not study the effects of silver nanomaterials on pathogenic bacteria or dental hard tissues. The remaining 66 publications that met the eligibility criteria were included in this review. The studied silver nanomaterials are classified as silver nanoparticles (n=21), silver fluoride nanoparticles (n=7), silver nanoparticle resins (n=31).,

Table 1 Publications on Silver Nanomaterials and Cariogenic Bacteria

Application of silver nanomaterials in tooth decay prevention

21 publications have studied the use of silver nanoparticles to prevent tooth decay. Eighteen of them reported the synthesis of silver nanoparticles and silver nanomaterials, which have the potential to manage caries. One study used silver nanoparticles in dentifrice. 15 One study reported that coating silver nanoparticles on orthodontic brackets to prevent tooth decay. Seven studies have reported the use of fluoride SNPs for early enamel remineralization and prevention of dentin caries.. 16 – 22 31 studies used silver nanoparticles to prevent tooth decay. Silver nanoparticles have been added to restorative materials, such as resins and adhesives, to prevent secondary decay.. 23 ,24 Các Silver nanoparticles are also incorporated into the resin of orthodontic materials, such as adhesives, elastomers and removable spacers, to prevent tooth decay.  A clinical trial reported that dental fillings with SNPs were superior to traditional fillings in preventing caries in first permanent molars. 26 Seven studies examined glass ionomer cements with  SNPs for the prevention of tooth decay. Six of them used ionomer glasses with silver nanoparticles as orthodontic cements to prevent tooth decay. The remaining research applies it as a restorative material to prevent secondary caries. 27

Effect of silver nanomaterials on Cariogenic bacteria

Most of the publications (59/67) showed that silver nanomaterials have antibacterial effects mainly against Streptococcus mutans. Table 1 Summary 59 published research on antibacterial effects of silver nanomaterials against pathogenic bacteria. Among them, studies measured antibacterial properties using monotypic bacteria, such as Streptococcus, Lactobacillus, Enterococcus and Pseudomonas , and studies used oral microcosm. Most studies measured bactericidal properties in vitro, while only four were performed in vivo, including two animal studies and two clinical trials.. 13 , 28 – 30 The results of the minimum inhibitory concentration and the minimum bactericidal concentration of silver nanomaterials against pathogenic bacteria have been highly variable in different studies. 31 – 33 The agar diffusion test demonstrated that the disc treated with SNPs material had a larger zone of inhibition than that treated with water. 34 In addition, the number of colony forming units demonstrates that silver nanomaterials have the ability to inhibit bacterial growth. 29 They also revealed that biofilms treated with silver nanomaterials had fewer bacteria than membranes treated with water. 35 The survival rate of bacteria in the biofilm was significantly lower after the application of silver nanomaterials than after the application of water. 36 Furthermore, biofilms treated with SNPs reduced metabolic activity, lactic acid production and glucosyltransferase gene expression.. 37 It has been shown that silver nanoparticles with smaller sizes have stronger antibacterial effects. 38 Meanwhile, the antibacterial properties improved with increasing concentration of silver nanoparticles in the material. 39 Capping agents can also affect the bacteriostatic action of silver nanoparticles. 40

Effect of silver nanomaterials on enamel and dentures

Several (11/67) studies reported inhibition of enamel and dentin demineralization under acid or cariogenic effects. Table 2 summarizes published studies on the influence of silver nanomaterials on the mineral content of enamel and dentin. Acoustic glazes treated with silver nanomaterials had a shallower depth of injury than glazes treated with water after biofilm challenge. 23 Also, artificially decayed enamel can be treated with silver nanoparticles to increase micro-hardness. 41 An orthodontic frame coated with silver nanoparticles reduces the incidence of caries on the incisor surface in the rat mouth. In addition, resins with silver nanoparticles can increase the microscopic hardness of caries after acid challenge (pH cycle). A dental filling with silver nanoparticles reduced mineral loss of children’s first molars in a clinical trial. 26 Six studies investigated the remineralization effect of fluoride SNPs. Acoustic glaze treated with nanosilver fluoride has similar value in micro-hardness to glaze treated with sodium fluoride. 18 , 19 The micro-hardness value of enamel caries treated with nano silver fluoride was higher than that of caries treated with sodium fluoride. 20However, no difference in mineral content could be detected between decayed enamel treated with nano silver fluoride and sodium fluoride by optical coherence tomography. 16 Nano silver fluoride prevented tooth decay in children in two clinical trials. 17 , 21

Table 2 Claims on silver nanomaterials and tooth mineral content (n = 11)

Discussion about silver nano
Although no time limit was used as part of the search strategy, publications using silver nanomaterials for caries control appeared in 2008. Almost half (32/67.48) %) of these publications were published between 2016 and 2019. Silver nanoparticles of different sizes, concentrations, and with different composites have been synthesized to investigate the usability their use in preventing tooth decay. The researchers also combined silver nanoparticles with other nanoparticles, such as calcium glycerophosphate and zinc oxide, to develop multifunctional nanocomposites to prevent tooth decay.
Sodium fluoride with SNPs may act as a strategy to prevent and capture tooth decay. In addition, the addition of SNPs to restorative materials, such as adhesives and resins, can prevent secondary caries without affecting the mechanical properties. Silver nanoparticles can further be used in orthodontic treatment to prevent primary caries by collaborating with adhesives, brackets, elastic cords and removable retainers.
Studies have used cariogenic monotypic strains of the genera  Streptococcus, Lactobacillus, Enterococcus, Pseudomonas  and  Candida  to demonstrate the antibacterial effect of silver nanomaterials on microbial growth.. 33 , 34 , 40
Streptococcus mutans  are the bacteria commonly used in these studies. These are the most common pathogenic bacteria found in a severe lesion.
Streptococcus mutans  is also implicated in the initiation and progression of dental caries. In the oral environment, bacteria collect in the extracellular matrix to form biofilms. Biofilms can increase the resistance of microorganisms to antimicrobial agents by impeding their transport.42 Therefore, the inhibitory effect of biofilm adhesion is very important. important for estimating the antibacterial efficacy of silver nanomaterials. Some researchers have chosen the mono-species biofilm model in their study because it is stable and easy to operate. However, monotypic biofilms are very different from dental biofilms. Dental biofilm is a complex ecosystem containing 1000 species of bacteria. In addition, microarrays were cultured using materials composed of various bacteria and extracellular matrix removed from the oral medium. It can effectively simulate the complexity and heterogeneity of biofilms in the human mouth.
Therefore, the miniature model frequently selected in the publications has been evaluated to test the antibacterial effect of silver nanomaterials.39 , 44 In situ models are still needed to test the anti-biofilm efficacy. study because even miniature models cannot fully mimic the actual oral environment. Four claims use an animal study or clinical trial to capture the true antibacterial effect of silver nanomaterials. 13 , 28 – 30

Silver nanoparticles give antibacterial effect to silver nanomaterials. Although the exact mechanism of the antibacterial effect of silver nanoparticles has not been fully elucidated, different antibacterial activities have been proposed. Silver nanoparticles can release silver ions. The released silver ions can enhance the permeability of the cytoplasmic membrane and lead to the disruption of the bacterial envelope. After penetrating the cell membrane, silver ions can inactivate respiratory enzymes and disrupt the production of adenosine triphosphate. Silver ions can also inhibit deoxyribonucleic acid replication and protein synthesis. 45

In addition to releasing silver ions, SNPs can kill bacteria on their own. SNPs can accumulate in pits that form on the cell wall after they attach to the cell surface. In addition, the accumulated silver nanoparticles can cause denaturation of cell membranes. Silver nanoparticles are also capable of penetrating bacterial cell walls and subsequently altering the structure of cell membranes due to their nanoscale size. 46

The antibacterial effect of SNPs against pathogenic bacteria is related to the properties of silver nanoparticles in nanomaterials. The literature reviews concluded that the smaller silver nanoparticles exhibited stronger antibacterial activity against planktonic Streptococcus mutans. . 31 , 38 , 47 – 49

Small silver nanoparticles are easy to release silver ions due to their larger surface-to-volume ratio. A large number of silver ions are released strongly increasing the inhibitory effect of silver nanoparticles.

In addition, capping agents affect the ability of silver nanoparticles to inhibit pathogenic bacteria . 40

The capping agents alter the surface of the SNPs and subsequently the dissolution efficiency of the SNPs. Positively charged SNPs have potent bactericidal activity against Streptococcus mutans . On the other hand,  Cariogenic bacteria, such as  Streptococcus mutans , have a negatively charged cell membrane.
Positively charged SNPs tend to approach pathogenic bacteria due to the presence of electrostatic attraction between them. In general, silver nanoparticles showed effective inhibition on both gram-positive and gram-negative bacteria. Note that gram-negative bacteria are generally more resistant to antibiotics than gram-positive bacteria. The outer cell membrane of gram-negative bacteria acts as a unique barrier to prevent many antibiotics from entering the cell.
In addition, silver nanoparticles are nano-sized, which can contribute to penetration into the outer cell membrane. Most of the studies used silver nanoparticles smaller than 50 nm in size, as larger silver nanoparticles would have a harder time penetrating the biofilm.. 51

Silver nanomaterials reduce lactic acid production in biofilms. It is incidental evidence that silver nanomaterials have the ability to reduce tooth demineralization. The assessment of mineral content is essential to demonstrate that silver nanomaterials can inhibit tooth demineralization. Soundproof enamel treated with SNPs reduces mineral loss after biofilm challenge. This demonstrated that SNPs could prevent tooth decay by reducing the demineralization effect through reducing the acid produced by the biofilm. A study using chemical modeling (i.e., no bacteria) showed that silver nanoparticles increased the microscopic hardness of enamel caries. SNPs can penetrate severe lesions and attach to hydroxyapatite crystals.20

In addition, silver ions released from SNPs can produce insoluble silver chloride on dental hard tissues. Precipitated silver nanoparticles and insoluble silver chloride increase the mineral density of dental hard tissue. In addition, silver nanomaterials can preserve exposed collagen in caries. In the oral environment, exposed collagen can be degraded by bacterial collagenase as well as by proteinases in saliva and dentin matrix, such as activated matrix metalloproteinase and cysteine ​​cathepsin. SNPs can inhibit and disable these enzymes. The preserved collagen can then act as a scaffold for the deposition of a mineral crystal and prevent further diffusion of calcium and phosphate.

Despite the fact that SNPs have a positive effect on the hard tissue of teeth, fluoride has a deeper remineralization effect than SNPs.. 23 , 41

Fluoride and its derivatives have been clinically used to prevent tooth decay. Fluoride can bond with calcium ions and hydrogen phosphate ions to form fluorapatite and fluorhydroxyapatite, which are more acid stable than hydroxyapatite. Fluoride also inhibits collagenase and thus impedes collagen degradation in dentin. Therefore, the researchers suggest using fluoride SNPs to promote remineralization of enamel and dentin.
Studies show that fluoride SNPs have a remineralization effect on caries using  optical coherence tomography and micro-hardness test. In addition, a clinical study demonstrated that nano silver fluoride was as effective as silver diamine fluoride in preventing tooth decay. However, nanosilver fluoride did not stain severe wounds with yellow, while silver diamine fluoride blackened severe wounds. However, many studies have not reported on the concentration of silver and fluoride nanoparticles. Therefore, further research is needed to investigate the optimal concentrations of SNPs and fluoride for the prevention of dental caries.
The toxicity of SNPs materials mainly depends on the free silver ions released from silver nanoparticles. Silver ions can penetrate mammalian cells, stimulating the production of reactive oxygen species. This increases oxidative stress and produces harmful effects.  SNPs exhibit lower cytotoxicity against human oral cells, such as gingival fibroblasts and dental pulp stem cells, compared with other silver compounds.  And resins containing SNPs  did not compromise the viability of the fibroblasts when they were dipped into the typical human salivary stream. No toxicity and side effects of 5% nano silver fluoride were observed in clinical trials. 17

Although silver nanomaterials have antibacterial and remineralizing properties, they are very susceptible to oxidation and agglomeration. The stability of silver nanomaterials is an important factor affecting the antibacterial effect of silver nanomaterials. However, no publications have reported their long-term stability, and very few studies have investigated the long-term antibacterial effects of SNPs..

Conclusion

In this review, the silver nanomaterials used for the prevention of tooth decay were classified as silver nanoparticles, silver nanoparticle resins, glass SNPs polishing agents, and nano silver fluoride. Silver nanomaterials can inhibit the growth of pathogenic bacteria and the adhesion of biofilms. They also inhibit collagenase activity and preserve the collagen matrix. In addition, they also interfere with the demineralization of enamel and dentin. Therefore, silver nanomaterials are promising materials for the prevention of dental caries. Because most studies are laboratory studies, further clinical studies are needed before they can be used to care for patients.

References: Use of Silver Nanomaterials for Caries Prevention: A Concise Review

Yin IX, Zhao IS, Mei ML, Li Q, Yu OY, Chu CH