Antimicrobial effect of silver diamine fluoride (SDF) in arresting dentine caries of permanent teeth: A Systematic review

Search strategy

An electronic search was conducted using the Google Scholar, Cochrane Library, and PubMed databases. All published in vitro and in vivo studies from January 2010 to September 2022 were included. The review question was formulated using the PICO framework: “Does silver diamine fluoride (I) have an antimicrobial effect (O) on dentinal caries in permanent teeth (P)?” The search keywords used were: (permanent teeth) AND (caries arrest) AND ((SDF) OR (silver diamine fluoride)) AND ((antimicrobial effect) OR (microbial reduction)) AND ((dentin caries) OR (dentinal caries)).

Inclusion and exclusion criteria

The inclusion criteria were:

The exclusion criteria were:

Data collection

Research articles were collected using Mendeley Desktop 1.19.8 for Windows. The electronic data search and analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy and results are summarized in a PRISMA flow diagram (Figure 1).

Figure 1. PRISMA flow diagram.

Screening process

Initially, 566 records were identified and collected from the three databases. After removing 16 duplicates, 40 non-English language articles, 55 theses, 31 books, and 4 conference proceedings, the remaining records were screened. Titles and abstracts were reviewed, and articles meeting the predetermined inclusion criteria were selected. Nine studies were retrieved, and their full texts were screened to ensure they met the eligibility criteria. References from the selected articles were also reviewed to identify additional studies for inclusion.

Data extraction and analysis

Data extraction and analysis were conducted by two authors independently in multiple steps. Any discrepancies were resolved by a third reviewer, who independently reviewed the articles, and a decision was made based on the majority consensus. The extracted data included study design, sample size, interventions, outcomes, and conclusions.

Risk of bias assessment

The risk of bias was assessed using the Cochrane Collaboration assessment tool to evaluate the methodological quality of the included studies. Each researcher conducted the risk assessment independently, and any disagreements were discussed and resolved to reach a mutual decision. The risk of bias for each study was documented as low, unclear, or high and summarized in Table 1.

Table 1. Risk of bias assessment for each article.

: low risk, : unclear risk, : high risk

	Studies	Random sequence generation	Allocation concealment	Blinding of participants and personnel assessment	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
1	Abdullah, et al., 202011
2	Karched et al., 201916
3	Ollie Y. Yu et al., 201810
4	Hertel et al., 201815
5	Irene Zhao et al., 201714
6	Mei et al., 20138
7	Mei et al., 201312
8	Mei et al., 201313
9	CHY et al., 20119

Data synthesis

A narrative synthesis of the results was performed due to the heterogeneity of the included studies. The antimicrobial effect of SDF on dentinal caries in permanent teeth was evaluated based on the reported outcomes. Meta-analysis was not conducted due to the variability in study designs, sample sizes, and outcome measures. Table 2

Ethical considerations

As this study is a systematic review, it does not involve direct human or animal subjects, and thus, ethical approval was not required. However, all included studies were checked for their ethical approvals and declarations of informed consent.

In vivo and in vitro studies

Seven clinical studies were retrieved to investigate the effect of SDF treatment on dentinal caries in permanent teeth.

Mei et al., 2013 evaluated the effect of 38% SDF on cariogenic biofilms and dentin carious lesions using five common cariogenic bacteria. Twelve dentin blocks were treated with SDF, and 12 with water, then incubated for 21 days. The results showed reduced bacterial growth and improved tooth mineral content in the SDF group compared to the control group (p < 0.01).⁸

In 2011, Chu et al. conducted a study to examine the effects of SDF on dentine caries induced by Streptococcus mutans and Actinomyces naeslundii using artificially demineralized human dentine blocks. The results indicated reduced biofilm counts in the SDF group compared to the control (p < 0.01). Surfaces of carious lesions due to S. mutans were harder (p < 0.05) in the SDF group, while calcium and phosphate content also showed significant reductions after SDF treatment (p < 0.05). These findings suggest that SDF has antimicrobial activity against cariogenic biofilms of both bacteria and slows down dentine demineralization.⁹

Yu et al., 2018 conducted a study on the effects of SDF solution followed by NaF varnish in treating dentine caries. They used 104 dentine blocks from human third molars, with different groups receiving various treatments and assessments for demineralization and biofilm. The results indicated that the combination of SDF and NaF had a more significant effect on lesion depth compared to individual treatments, showing higher antibacterial effects as well.¹⁰

Abdullah et al., 2020 conducted a study to assess the antimicrobial effectiveness of various SDF materials. They used in-situ biofilms from five participants and allowed them to grow for 6 hours. The study compared the anti-biofilm efficacy of different concentrations of SDF, as well as combinations with potassium iodide. The results indicated that all samples treated with 38% SDF showed a significant decrease in viable bacteria compared to the negative control (sterile distilled water). There was also no additional antibacterial effect observed when KI was supplemented with SDF.¹¹

Mei et al., 2013 conducted an in vitro study to investigate the antimicrobial effect of SDF on Streptococcus mutans and Lactobacillus acidophilus co-cultured dual-species biofilm and dentine caries lesions. Dentine blocks from human third molars were inoculated with bacteria, divided into test and control groups, treated with SDF or water, and incubated for 7 days at 37°C. The results showed a significant reduction in CFU counts of both bacteria in the SDF group compared to the control group. SEM images indicated that more bacteria were dead in the SDF group than in the control group. CLSM images also demonstrated a higher dead-to-live ratio after SDF application compared to water. FTIR analysis revealed differences between the log Amide I:HPO42- ratio of the two groups, as did gold-labeling density.¹²

Mei et al. (2013) further investigated the antagonistic impact of 38% SDF on demineralized dentin. The experiment included 18 blocks of demineralized human dentine that were divided into four groups: one that received a 38% SDF solution, another that received a 10% sodium fluoride solution, a fourth that received a 42% silver nitrate solution, and the control group received deionized water. In the SDF group, smooth, unexposed collagen fibers of dentin were observed. Some collagen fibers were exposed and relatively rough in the sodium fluoride group. In contrast, demineralization resulted in evident exposure of collagen fibers in the silver nitrate and water groups. The mean lesion depth of the silver nitrate and water groups were 259 ± 42 mm and 265 ± 40 mm, respectively, which were significantly higher than those of the SDF and sodium fluoride groups, which were 182 ± 32 mm and 204 ± 26 mm, respectively. The amount of hydroxyproline (HYP), a non-proteinogenic amino acid, in the remineralization solution was used to measure collagen degradation. In contrast to the water (469 ± 63 mg/mL) and sodium fluoride (189 ± 85 mg/mL) groups, the amounts in the SDF (346 ± 57 mg/mL) and silver nitrate (349 ± 18 mg/mL) groups were noticeably higher.¹³

Irene Zhao et al. (2017) performed an in vitro investigation to see whether a silver nitrate solution and a sodium fluoride varnish might halt the progression of caries. A total of fifty-four dentine slices taken from human third molars were demineralized and processed. After that, the slices were split into three groups: SF, which consisted of 25% silver nitrate and 5% sodium fluoride varnish; SDF, which was a 38% silver diamine fluoride solution and was used as a positive control; and deionized water, which as a negative control. The water group showed exposed dentine collagen fibres, but the SF and SDF groups showed intact and smooth fibres, according to scanning electron microscopy. Both the SDF and SF groups showed less depth of lesion in typical micro-CT images when compared to the water group. There was a statistically significant difference between the water group’s lesion depth (258 ± 53 μm) and the SDF and SF groups, with the former having a mean lesion depth of 135 ± 24 μm and the latter of 128 ± 19 μm, respectively. Moreover, in comparison to the water group (339 ± 16 μg/ml), the SF and SDF groups had a noticeably reduced concentration of hydroxyproline (HYP) in the remineralization solution (312 ± 11 μg/ml and 317 ± 16 μg/ml, respectively).¹⁴

SDF behavior on occlusal and root dentin caries

Hertel et al.’s 2018 in vitro study aimed to assess the bactericidal efficacy of silver diamine fluoride (SDF), cold atmospheric plasmas (CAPs), and chlorhexidine (CHX) in root caries lesions. They created artificial root carious lesions in 50 human dentin samples, dividing them into four groups: two test groups (plasma jet and dielectric barrier discharge source) and two control groups (CHX and SDF varnishes), with a negative control group treated using a blank micro brush to remove nonadherent biofilm. All applied agents resulted in significantly lower colony-forming unit (CFU) counts compared to the control (p ≤ 0.01). When comparing the four treatment agents, only SDF showed a significant decrease in CFU counts (p = 0.004) compared to the dielectric barrier discharge source.¹⁵

On the other hand, Karched et al.’s 2019 in vivo study aimed to determine the antimicrobial efficacy of SDF and SDF with potassium iodide. They conducted their study on five patients, each with at least five lesions. Four different agents (SDF, SDF + potassium iodide, chlorhexidine, and sterile saline) were applied to four carious lesions separately in each patient. The mean inhibition zone of S. mutans CCUG 11877 was 25.7 mm, displaying the highest susceptibility to SDF. In the SDF + KI group, the inhibitory zone decreased to 15.15 mm. The inhibition zone of chlorhexidine was 23 mm, while no inhibition was observed in the negative control saline group. The total viable counts of anaerobes were reduced by over 90% after treatment with SDF or SDF + KI, with complete reduction observed in total viable counts of mitis salivarius-bacitracin (MSB) agar. Treatment with SDF decreased the median CFU counts from 9 × 105 to 1.6 × 102 per mg dentin, while in the SDF + KI group, the counts reduced from 2.9 × 105 to 9.2 × 10 per mg dentin. Treatment with chlorhexidine also significantly reduced the median CFU counts. Lesions treated with sterile saline showed no effect on viable counts. Following treatment with SDF, complete inhibition of bacterial growth on Brucella agar was observed in two out of five subjects, with all subjects treated with SDF showing no bacterial growth on MSB agar plates. Complete inhibition of bacterial growth was evident in four out of five subjects following SDF + KI treatment.¹⁶ Neither study mentioned a difference in the mechanism of action or behavior of SDF in the crown or root of the tooth. All studies revealed bacterial inhibition after using SDF in both root and occlusal caries.