Dentin–Pulp Interaction with Silver Diamine Fluoride

Abstract

Silver diamine fluoride (SDF) is increasingly used as a non-invasive treatment modality for caries management, particularly in pediatric and geriatric populations. Understanding its impact on the dentin–pulp complex is crucial for assessing its efficacy and safety in preserving pulp health while arresting carious lesions. SDF application directly affects the dentin–pulp complex by interacting with dentin, potentially influencing pulp health and function. Exploring how SDF interacts with dentin and its effects on pulp tissue would provide valuable insights into the dentin–pulp complex. Also, dentists and clinicians need to be aware of the potential effects of SDF on the dentin–pulp complex when considering its use in caries management protocols. Discussing clinical considerations, such as indications, contraindications, application techniques, and patient selection criteria, would be valuable for dental practitioners.

1. Introduction

Silver diamine fluoride (SDF) has emerged as a valuable tool in contemporary dentistry, particularly for its unique properties in arresting dental caries and managing hypersensitivity. This innovative solution, composed of silver, fluoride, and ammonia, presents a non-invasive approach to caries management, especially in populations where traditional restorative interventions may be challenging or impractical.

Beyond its antimicrobial and remineralizing properties, SDF has gained attention for its efficacy in managing dentin hypersensitivity, a common complaint among patients. The application of SDF results in the formation of a silver protein layer over exposed dentin tubules, effectively blocking the transmission of stimuli that cause sensitivity, thereby providing relief to patients.

In recent years, SDF has garnered significant interest due to its simplicity of application, cost-effectiveness, and potential to improve oral health outcomes, particularly in underserved communities and pediatric populations. However, despite its promise, concerns persist regarding its esthetic impact, potential discoloration, and long-term effects on dental tissues, especially the dental pulp.

Understanding the interaction between SDF and the dental pulp is crucial for optimizing its clinical application and ensuring patient safety. This chapter aims to explore the chemistry, mechanisms of action, clinical applications, and potential impacts of SDF on dental pulp tissues, shedding light on its role in modern dental practice and guiding evidence-based decision-making.

2. Chemistry and mechanism of action of SDF

SDF’s mechanism of action is multifaceted. It leverages silver ions to inhibit the growth and metabolism of cariogenic bacteria, thereby halting the progression of dental caries. Fluoride ions contribute to the remineralization of enamel and dentin, promoting the formation of fluorapatite crystals, which enhance the structural integrity of the tooth. This dual action not only arrests decay but also fortifies tooth structure, offering a conservative alternative to conventional restorative treatments.

SDF is a transparent aqueous solution of silver ions and fluoride ions. Unlike silver fluoride (AgF), SDF exhibits a lower alkalinity with a pH ranging between 8 and 9. This characteristic eliminates the need for a reducing agent, simplifying its application process. SDF is recognized for its stability and ability to maintain a consistent concentration over time, making it a preferred choice for caries arrest in various countries, including China and Japan [1]. The longevity of SDF’s effectiveness in halting dental caries has been established through years of practical application and research.

Fung et al. [2] proposed that SDF exerts its effects through two primary mechanisms: fluoride ions primarily act on the tooth structure, while the silver phosphate component combats cariogenic bacteria. When applied, SDF interacts with the hydroxyapatite in enamel, resulting in the formation of fluorapatite [Ca10(PO4)6F2], which has demonstrated greater resistance to acidic environments compared to hydroxyapatite. Furthermore, SDF exhibits antimicrobial properties against Streptococcus mutans and Actinomyces naeslundii on dentin surfaces. Studies have also indicated that SDF inhibits the adherence of biofilms, consequently reducing bacterial colonization on enamel surfaces. The characteristic black-stained layer associated with arrested dentin caries manifests as a durable and impermeable layer of silver phosphate, effectively shielding collagen exposure [3]. These findings underscore the multifaceted nature of SDF’s action, highlighting its potential in caries management and microbial control.

Research findings indicate that SDF does not provoke inflammation or necrosis of the dental pulp. Furthermore, studies have demonstrated the potential for SDF to stimulate the formation of tertiary dentin. These observations suggest that SDF holds promise as a viable option for indirect pulp therapy in cases involving deep cavities. This characteristic underscores its potential as a conservative approach to managing deep carious lesions while preserving pulp vitality and promoting dentin repair. However, further research and clinical studies are necessary to validate its efficacy and safety for such applications [4].

3. Clinical applications of SDF

SDF serves as a non-invasive treatment option for managing dental caries, alleviating dentin hypersensitivity, and promoting preventive dental care. Its effectiveness, ease of application, and cost-efficiency make it a valuable tool in various clinical scenarios, ranging from pediatric dentistry to geriatric care. The scope of clinical applications of SDF can be divided into the following categories:

3.1 Pediatric dentistry

SDF proves to be an effective solution for managing early childhood caries, particularly in cases where children may exhibit challenges in cooperation or understanding, rendering them unsuitable candidates for conventional restorative treatments. Additionally, it offers a practical approach when children present with multiple cavitated lesions, potentially reducing the need for multiple visits to address each lesion individually.

3.2 Geriatric dentistry

Older adults often face unique oral health challenges that increase their susceptibility to dental caries. Factors such as exposed root surfaces, periodontal disease, and systemic conditions or medications altering oral flora contribute to their heightened risk. These conditions necessitate tailored dental care approaches to address their specific needs and ensure optimal oral health outcomes. Exposed root dentin resulting from gum recession is susceptible to demineralization at a pH level less acidic than that required for enamel demineralization, exacerbating the risk of dental caries. A substantial portion of tooth decay is attributed to recurrent disease linked with deteriorating restorations. Notably, the majority of dental caries observed in older adults stems from restoration failure specifically at the gingival margin [5]. These lesions can be specifically challenging to restore efficiently.

3.3 Special needs

SDF can be used to manage dental caries in patients with special needs who may have difficulty complying with traditional restorative treatments or who require a less invasive approach to dental care. Many special needs patients experience sensory sensitivities or sensory processing disorders. SDF application is quick and minimally invasive, reducing the potential for sensory overload or discomfort during dental visits. Special needs patients often face challenges with oral hygiene maintenance, putting them at a higher risk for dental caries. SDF can be applied preventively to halt the progression of early carious lesions and prevent the need for more extensive dental treatments in the future. In a recommendation by Crystal et al. in 2017, [6] 38% SDF was advocated to be effective in arresting cavitated caries lesions in children and adolescents, including those with special health care needs.

3.4 Community health care setting

Dental public health initiatives and programs aim to optimize caries prevention and management strategies that are minimally invasive, safe and simple to administer, affordable, and can be carried out by various members of dental treatment teams [7]. Furthermore, in the context of the widespread transmission of the SARS-CoV-2 virus (COVID-19), SDF has emerged as a recommended caries management procedure that is non-surgical, non-aerosolizing, and aligns with directives from public health authorities, regulatory agencies, and professional organizations aimed at minimizing the risk of airborne pathogen transmission [8]. SDF fulfills all these criteria and recent evidence also indicates the acceptance of SDF among dentally underserved patient groups for its application in posterior dentition. When presented to parents as a safe, minimally invasive, and effective alternative to potentially painful procedures or those requiring sedation for their children, SDF has been favored, especially for children with behavioral challenges [9].

4. Interactions of silver diamine fluoride with dentin and dental pulp

4.1 Direct effects

4.1.1 Pulpal irritation and cytotoxicity

In a study by Hosoya et al. direct application of SDF on dental pulp caused severe inflammation and necrosis of dental pulp [10] in most of the teeth in the experimental group. This result was attributed to the high toxicity of silver ions and the short follow-up period that may not have allowed the pulp to clear the SDF out through normal circulation [10]. In the same study, one tooth demonstrated the formation of tertiary dentin after 30 days of direct application of SDF on dental pulp. This finding was credited to the host immune response.

The SDF solution can swiftly penetrate dentin. A concern arises regarding the potential cytotoxic effects on the dentin–pulp complex due to the abundance of reactive ions in SDF. Studies have shown that reactive ions, such as silver ions, can permeate dentin to a depth ranging from 5 to 40 μm [11]. Some studies have also detected penetration of silver precipitates deeper than 2 mm in artificially demineralized dentin [12] and primary teeth [13]. In another study by Shijia Hu et al., it was demonstrated that the application of 38% SDF in teeth with a remaining dentin thickness of less than 1.0 mm, SDF was capable of causing the death of viable dental pulp stem cells [14]. A more recent study evaluated pulp cell response to SDF and potassium iodide and concluded that SDF applied alone caused cytotoxic effects on dental pulp, but a combination of SDF+ KI reduced the cytotoxic effects [15].

Studies have indicated that the toxic effects of silver and fluoride ions include depletion of glutathione and elevated oxidative stress or lipid peroxidation [16]. These processes diminish the antioxidant capabilities within the dental pulp, ultimately leading to cellular death and inflammation. Furthermore, research has demonstrated that the cytotoxic impact persists even after rinsing hydroxyapatite discs treated with SDF for 77 days [17]. In response, a proposed solution involves the application of glutathione alongside SDF to bolster antioxidant functions and mitigate the toxic effects exerted by SDF on dental pulp cells [16].

It has been studied that different chemical forms of silver may affect the viability of pulp cells to varying levels. Also, the nature of remaining dentin could affect the level of penetration of SDF. The remaining carious dentin could potentially be comprised of less tubular dentin or translucent dentin, or could even be partially or completely obstructed with sclerotic dentin [18].

4.1.2 Tertiary dentin formation

Tertiary dentin can be categorized as either reactionary or reparative in nature. Reactionary dentin is produced by existing odontoblasts, whereas reparative dentin is synthesized by newly differentiated odontoblast-like cells. Numerous factors influence the formation of tertiary dentin, including the method of cavity preparation, the condition of the dentin–restoration interface, the presence of bacteria, the type and application technique of the restorative material employed, and the amount and nature of remaining dentin thickness, among others.

An in-vivo comparative study by Korwar et al., conducted histological analysis, showcasing the deposition of tertiary dentin within the space between the pulp and the remaining dentin thickness [4], suggesting that SDF can be effectively used as an indirect pulp therapeutic agent. In a study conducted by Gotjamanos, silver fluoride displayed a positive pulp response, marked by the presence of ample reparative dentin and a broad odontoblastic layer [19].

Following SDF application, dentin remineralization is facilitated, resulting in the formation of an outer layer of highly mineralized dentin measuring approximately 150 μ. This layer exhibits a notable presence of calcium and phosphate ions [20] As a result of this remineralization process, dentin carious lesions treated with 38% SDF demonstrate increased microhardness. Microhardness serves as an indirect measure, or surrogate outcome, to gauge alterations in the mineral content of mineralized tissue. This effect was demonstrated in an ex vivo study involving primary upper anterior teeth with dentin carious lesions, which received 38% SDF treatment (administered once every 12 months) [21].

In a recent case report and review of literature, D. Mudumba illuminated a compelling instance of reparative dentin formation observed in a primary molar. This phenomenon effectively obviated the necessity for a more extensive pulp therapy procedure [22].

4.2 Indirect effects

4.2.1 Pulp cell activity after indirect application

The indirect application of SDF has been shown to increase the activity of pulpal cells adjacent to the carious lesion. It was also observed that the odontoblasts within the pulp close to the area of SDF application retained their flattened appearance [23]. This shape of odontoblasts might indicate their status after forming tertiary dentin3 [24]. Another indication of change in odontoblastic activity after SDF application is the presence of the Line of Owen that marks changes in cellular activity [4].

4.2.2 Antimicrobial activity

Oral flora is comprised of numerous species of bacteria, but Streptococcus, Lactobacillus, and Actinomyces naeslundi have been found to be associated with dentin and root caries [25]. The antimicrobial nature of SDF can be attributed to silver and fluoride ions. Silver ions are well-known for their broad-spectrum antimicrobial properties. They have the ability to disrupt multiple cellular processes in microorganisms, including bacterial cell wall synthesis, DNA replication, protein function, and enzymatic activity. Upon application, silver ions released from SDF penetrate the bacterial cell membrane, leading to structural damage and cell death [26]. Silver ions can also inhibit bacterial adhesion and biofilm formation on tooth surfaces, thereby reducing the colonization and growth of cariogenic bacteria like Streptococcus mutans and Lactobacillus species. Additionally, in a recent investigation by Sulyanto et al. (Figure 1) examining the impact of SDF on microbial communities within subsurface dentin with the help of 16S rRNA gene amplification and sequencing, it was found that SDF did not have much effect on microbial population on dentin surface but definitely altered the microbial composition deep within the dentin tubules [27].

Figure 1.

The impact of silver diamine fluoride (SDF) treatment on the microbial population within dentin structures.

Silver ions exhibit high reactivity and have a strong affinity for thiol groups (SH), which are prevalent in enzymes. When silver ions bind to these thiol groups, they denature the enzymes, rendering them non-functional. Consequently, the organism’s energy system is disrupted, leading to the inability to maintain osmotic pressure. This disruption ultimately results in leakage of vital substrates, leading to cellular death [28].

The reaction of SDF with the thiol groups is based on the following equation:

$$\text{A}/\text{N}-\text{SH}+\text{AgX}\to \text{A}/\text{N}-\text{S}-\text{AgX}+\text{HX}$$E1

(A/N is amino or nucleic acid; SH is the thiol group; Ag is silver; and X is diamine fluoride).

SDF inhibits the formation of biofilm and caries progression by killing bacteria [29]. SDF is effective against Streptococcus mutans and also Actinomyces, Lactobacilli, and other species [30]. Silver particles observed on the dentin surface following SDF treatment in vitro have been correlated with reduced bacterial counts and an increased presence of deceased bacteria [30]. Further in vitro investigations have demonstrated that SDF exhibits superior efficacy against Streptococcus mutans compared to silver nitrate or sodium fluoride alone. This suggests the combined contributions of both the silver and fluoride components of SDF to its potent antibacterial activity [30]. Alongside its cariostatic properties, the application of 38% SDF creates an environment that hinders the activation of dentin collagen enzymes [31].

Dentine surfaces treated with SDF exhibited significantly lower growth of Streptococcus mutans compared to untreated surfaces [32]. It was also demonstrated in another study that the colony-forming unit (CFU) counts of monospecies strains of Streptococcus mutans and Actinomyces naeslundii were notably reduced following SDF application, with few viable bacteria remaining [3]. Furthermore, CFU counts of dual-species biofilms containing Streptococcus mutans and Lactobacillus acidophilus were markedly lower on demineralized dentine treated with SDF compared to those treated with water alone. Additionally, the dead-to-live ratios of bacteria were significantly higher after SDF application than after water application [33].

It was also noted in another study that the adhesiveness and growth of Lactobacillus casei, Streptococcus mutans, and Streptococcus oralis reduced after treating the surface with SDF [34].

4.2.3 Dentin remineralization

To understand the physiology of dentin remineralization, it is necessary to understand the following chemical reaction that takes place when SDF is applied to the tooth surface,

$$C{a}_{10}{\left(P{O}_4\right)}_6{\left(OH\right)}_2+Ag\left(N{H}_3\right)\text{2F}\to Ca{F}_2+{\text{AgPO}}_4+N{H}_{4}OH$$E2

(hydroxyapatite+ silver diamine fluoride calcium fluoride+ silver phosphate+ ammonium hydroxide)

Later, calcium fluoride dissociates into calcium and fluoride, leading to the formation of insoluble fluorapatite. The calcium fluoride formed after the application of SDF functions like a pH-regulated fluoride reservoir on the tooth surface [35]. It is important to note here that 38% of SDF contains 44,800 ppm fluoride, which is probably the highest among the fluoride agents in dentistry. This fluoride promotes the remineralization of carious dentin.

Also, silver phosphate is unstable and highly soluble and gets reduced back into silver ions that may react with the readily available chloride ions to form lower-soluble silver chloride (AgCl₂). The deposition of silver chloride causes the black appearance of tooth surface after the application of SDF [36]. The silver ions also react with the collagen in the dentin and get reduced to metallic silver. The more demineralized the dentin is, the more collagen is exposed and available to react with silver ions, thus resulting in more metallic silver formation. This process results in black discoloration [37].

4.2.4 Reduction in dentin hypersensitivity

There is still no consensus on the exact mechanism of dentin hypersensitivity, but Brannstrom’s hydrodynamic theory is the most plausible hypothesis. It states that any thermal, chemical, or mechanical stimuli can alter the direction or flow of dentinal tubular fluid, which in turn stimulates the A-delta fibers surrounding the odontoblasts.

SDF was cleared by The United States Food and Drug Administration in 2014 to treat dentine hypersensitivity. One proposed mechanism of action of SDF is the formation of a squamous layer formed by the aqueous solutions of silver and fluoride over the exposed dentin and that seals the dentinal tubules, thus reducing the fluid shift in the tubules that is responsible for sensitivity [10]. Another hypothesis is the formation of calcium fluoride by the interaction of fluoride ions and free calcium ions that block the dentinal tubules [38]. This calcium fluoride is partially soluble in saliva [39]. Scanning electron microscopic studies of SDF-treated dentin have revealed the presence of silver particles within the tubules, thereby decreasing their diameter and eventually decreasing the tubular fluid movement [40].

A systematic review by Piovesan et al. in 2023 concluded that 38% SDF is beneficial in treating dentin hypersensitivity, but longer evaluation periods are required to assess its efficacy in the long term [41]. Not much consistency has been seen in various studies testing the effect of SDF in reducing dentin hypersensitivity.

Castillo JL studied the clinical effectiveness of topical SDF as a desensitizing agent and concluded SDF to be safe and efficient in treating dentin hypersensitivity after 24 h and 7 days [42]. Another study analyzed the efficacy of SDF and CO₂ laser in dentin hypersensitivity and found a reduction in visual analog scale (VAS) and DIAGNOdent scores after the application of SDF alone or along with Co2 laser [43]. A more recent study evaluated the effectiveness of 38% SDF in reducing dentine hypersensitivity in exposed root surfaces in older Chinese adults. This study concluded that 38% SDF was more effective than 5% potassium nitrate solution in reducing hypersensitivity on exposed root surfaces [44].

5. Adverse effects of SDF

The most common adverse effects of the application of SDF are pulpal irritation, staining, and soft tissue irritation [29]. It has been studied that tooth staining can be reduced by the application of potassium iodide immediately after SDF [32].

Pulpal irritation is found to be more pronounced in deep cavities where the remaining dentin thickness is less than 1.0 mm [14]. Temporary staining on skin or submucosa resolves within 2 weeks by natural exfoliation [45].

In the event of accidental ingestion of a large volume of SDF, a 10% calcium gluconate solution can be administered to facilitate the formation of insoluble calcium fluoride that will eventually be eliminated from the body [45].

6. International guidelines

The American Academy of Pediatric Dentistry’s policy statement (2023) supports the use of SDF as a minimally invasive caries management option to prevent or delay the need for more extensive procedures and promotes the appropriate training and education to dental personnel in accordance with the respective state’s dental practice act. It also encourages further practice-based research aimed at evaluating the efficacy and impact of SDF on the health-related quality of life of infants, children, adolescents, and individuals with special healthcare needs [46].

7. Conclusion

In conclusion, SDF emerges as a valuable tool in contemporary dentistry, offering multifaceted benefits for caries management, dentin hypersensitivity relief, and preventive care. Its non-invasive nature, cost-effectiveness, and ease of application make it particularly well-suited for addressing the diverse needs of various patient populations, including children, older adults, and individuals with special healthcare needs. Moreover, amidst the challenges posed by the COVID-19 pandemic, SDF stands out as a safe and compliant alternative that aligns with public health guidelines. However, further research and practice-based studies are warranted to fully elucidate its long-term efficacy and impact on oral health-related quality of life across different demographics. Overall, SDF represents a promising advancement in modern dental practice, poised to enhance preventive care strategies and improve oral health outcomes for patients worldwide.

Conflict of interest

The authors declare no conflict of interest.