**1. Introduction**

The oral microbiota colonizes oral biofilm on the surface of the tooth or on the mucosa within the mouth. The accumulation of oral biofilm can lead to oral diseases such as dental caries or periodontitis [1]. Oral biofilm can lead to dental caries in two ways. First, bacteria within the oral biofilm produce acid through sugar metabolism. Second, the acid causes a subsequent decrease in the environmental pH value. Both of the above are responsible for the demineralization of the tooth surface and the formation of dental caries [2]. The amount of tooth mineral and other calcium phosphates in the plaque fluid decreases rapidly after exposure to fermentable carbohydrates. Lactic acid production and a reduction in the plaque fluid volume can result in the formation of caries [3].

Acid-base-producing bacteria, in varying numbers and proportions, are the key pathogens associated with dental caries [4]. Among the suspected acid-producing bacteria, *Mutans streptococci* (MS) has been confirmed, in a systematic literature review, to play a central role in the initiation of dental caries on both enamel and root surfaces [5]. This is the case for several reasons: first, MS is the most frequently isolated species from a caries

**Citation:** Zhang, J.; Got, S.-R.; Yin, I.X.; Lo, E.C.-M.; Chu, C.-H. A Concise Review of Silver Diamine Fluoride on Oral Biofilm. *Appl. Sci.* **2021**, *11*, 3232. https://doi.org/ 10.3390/app11073232

Academic Editor: Yoshiaki Nomura

Received: 26 February 2021 Accepted: 30 March 2021 Published: 4 April 2021

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lesion; second, MS is highly acidogenic and aciduric [6,7]; and third, MS can produce surface antigens I/II and water-insoluble glucan, which promote bacterial adhesion to the tooth surface and to other bacteria [6]. For the purpose of halting the closed circle of the process, an intervention that can inhibit the bacteria that produce acid is needed.

Silver diamine fluoride (SDF) has been widely used to prevent and arrest caries, and "silver diamine fluoride" is the most common spelling/keyword for this compound in the dental literature. SDF was approved for use as a therapeutic agent in Japan over 50 years ago [8]. It has also been used for dental caries treatment in Australia and in some countries in Latin America such as Argentina and Brazil for many years [9]. The Food and Drug Administration approved the marketing of SDF in the United States for the treatment of human dentinal hypersensitivity in adults in 2014 [10].

SDF contains silver and fluoride, which form a complex with ammonia in a colorless alkaline solution [9]. It is not only a combination of silver salt, ammonium, and fluoride ions but also a mixed heavy-metal halide co-ordination complex. Ammonia can provide an alkaline environment, thus keeping the solution constant for a certain period of time [11]. In addition, silver compounds have been reported to have antimicrobial properties in the application of medicine and dentistry for decades [12]. Fluoride is also used in various forms to prevent and arrest caries due to its remineralization function [9]. Therefore, SDF has been hypothesized to contain the combined effects of silver and fluorides.

Fluoride can inhibit the production and metabolic activity of certain strains of bacteria within biofilm at low concentrations [13]. At high concentrations, fluoride inhibits the growth of cariogenic bacteria in dental plaque [14]. One mechanism of biofilm inhibition is to bind its ions to the bacterial cell constituents and to influence enzymes such as enolase and proton-extruding adenosine triphosphatase [15]. Another mechanism is the inhibition of the carbohydrate metabolism of acidogenic oral bacteria [16,17]. However, this may contribute to the development of bacterial tolerance and shorten the duration of the antibacterial effect [18]. Nonetheless, the dominant advantage of fluoride is that the re-mineralizing effect, particularly for the SDF solution, effectively arrests dental caries [19].

Several reviews have been conducted regarding the clinical use of SDF for preventing and arresting dental caries with significant effect [20,21]. However, the rationale behind the impact of SDF on biofilm remains unclear. The aim of this systematic review was to identify the effect of SDF on biofilm. The study question was as follows: What is the effect of SDF on biofilm?
