Assessing the Potential Association Between Microbes and Corrosion of Intra-Oral Metallic Alloy-Based Dental Appliances Through a Systematic Review of the Literature

Objective: Systematic review assessing the association between oral microorganisms and corrosion of intra-oral metallic alloy-based dental appliances. Design: PubMed, Scopus, and Web of Science were searched using keyword combinations such as microbes and oral and corrosion; microbes and dental and corrosion; microorganisms and oral and corrosion; microorganisms and dental and corrosion. Results: Out of 141 articles, only 25 satisfied the selection criteria. Lactobacillus reuteri, Streptococcus mutans, Streptococcus sanguis, Streptococcus mitis, Streptococcus sobrinus, Streptococcus salivarius, sulfate-reducing bacteria, sulfate oxidizing bacteria, Veilonella, Actinomyces, Candida albicans were found to have a potential association with corrosion of intraoral metallic alloys such as stainless steel, titanium, nickel, cobalt-chromium, neodymium-iron-boron magnets, zirconia, amalgam, copper aluminum, and precious metal alloys. Conclusion: The included studies inferred an association between oral microorganisms and intra-oral metallic alloys-based dental appliances, although, it is vital to acknowledge that most studies in the review employed an in-vitro simulation of the intra-oral condition.


INTRODUCTION
Metals in their pure or alloy forms are commonly used in dentistry despite the introduction of advanced materials like resins and ceramics, which can be largely attributed to the mechanical properties of metallic alloys (Upadhyay et al., 2006). The intra-oral environment has several factors that could predispose such metal alloy-based dental appliances to corrosion. These factors include varying temperature, oxygenation, mechanical forces, acidity, and alkalinity of external agents (foods, drugs), microorganisms, local anaerobic environments (e.g., subgingival). Some of the metals used in dentistry are amalgams of silver-tin, copper, noble metal alloys of gold and silver palladium, base metal alloys of nickel, cobalt, iron, and titanium alloys. Though most of the alloys are passivized and resistant to corrosion, the susceptibility still exists because of the predisposing factors in the oral environment (Bayramoglu et al., 2000;Karov and Hinberg, 2001). The clinical relevance of corrosion of dental appliances in the oral environment is due to some major clinical implications. The first is the potential toxic risk posed by the corrosion by-products. The second is that the corroded dental appliance could lose its functional integrity. The risk of allergy to the unbounded metal elements when released by corrosion should also be considered. A study by zora et al. suggested that corrosion products may pose a risk in immunologically susceptible patients (Venclíková et al., 2007). The role of microorganisms in corrosion is extensively discussed in the sewage and pipeline industry, although the literature is relatively scanty when it comes to the biological environment, including the oral cavity (Mystkowska et al., 2018). Thus, the present systematic review was formulated to assess the association between microorganisms and corrosion of intra-oral dental appliances.

MATERIALS AND METHODS
The present systematic review adhered strictly to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Moher et al., 2009;Hutton et al., 2015) ( Figure 1).

Inclusion Criteria
In-vitro studies in the English language assessing the potential effect of intra oral micro organisms on corrosion of metallic alloy-based dental appliances.

Exclusion Criteria
In-vivo studies, reviews, letters, case reports/series, editorials. Articles not in the English language. Articles without sufficient details on either the microbe or the dental appliance, for invivo studies, due consideration to antibiotic use during sampling was checked. In-vivo studies were excluded as the research design could potentially play a major role in determining the final outcome. In addition, a prilimanary literature search revealed that at present, there are were no in-vivo studies which have assessed the effect of intra oral micro organisms on corrosion of metallic alloy-based dental appliances.

Focus Question
What is the effect of an intra-oral microorganism on the corrosion of intraoral metallic alloy-based dental appliances? (population -metallic alloy-based dental appliances, intervention-intra oral microorganisms, comparator-metallic alloy-based dental appliances without oral microorganisms, outcome-corrosion).

Search Strategy
PubMed, Scopus, and Web of Science were searched using various combinations of the following keywords: microbes and oral and corrosion; microbes and dental and corrosion; microorganisms and oral and corrosion; microorganisms and dental and corrosion. The identified articles were manually crossreferenced to identify further potential articles.

Study Selection and Data Extraction
• Identified articles were screened for relevance to the topic and potential duplicates using their titles and abstracts. • The full text of the screened articles was assessed using the selection criteria Two reviewers (UG and SV) independently performed steps 1 and 2. Kappa coefficient (κ) was calculated to assess interobserver reliability. Only studies satisfying the selection criteria were included in the qualitative analysis. Data including the study characteristics, design, assessment tools, the microbe, the metallic alloy assessed, results, and inference were extracted from these included articles. Due to the lack of a standard risk of bias tool for in-vitro studies, a customized risk of bias tool was formulated. The categorization in to high, medium, and low risk was based on Joanna Brigg's critical appraisal tool (The Joanna Briggs Institute, 2014;Normando et al., 2017).

Study Selection
Hundred and forty-one articles (PubMed-44; Scopus-64; Web of Science-12; Cross-reference-21) were identified in the search. Title and abstract screening led to the exclusion of 92 articles as they were either duplicate or lacked relevance to the topic of interest. Of the 49 articles subjected to full-text review, 24 articles were excluded as they did not fulfill the inclusion criteria (Supplementary Table 1). Only 25 articles met the eligibility criteria and were included in this review. Figure 1 summarizes the selection strategy employed in the qualitative analysis. Table 1 summarizes the data extracted from the studies included in the systematic review. Kappa coefficient (κ) for 1st and 2nd step of the review was 0.97 and 0.94, respectively indicating a good interreviewer reliability.

Risk of Bias
Of the 25 studies included, 4 studies had a low risk of bias and 4 studies had a high risk of bias. The rest of the studies (n = 16) had moderate risk of bias. The summary of the risk of bias assessment is presented in Table 2.    In vitro Pure Ti, Ti alloy, SUS, CoCr alloy, Ni-Cr alloy, Au-Ag alloy

Study Characteristics
Electric Potential for corrosion current

Streptococcus mutans and its products
The less noble materials (except CpTi grade II) showed their inferior corrosion resistance when they were exposed to media containing bacteria byproducts 24 L. Proenc/2015/Portugal  In vitro Ni-Cr-Mo alloy Open circuit potential measurements, cyclic voltammetry, linear sweep voltammetry, as well as electronic microscopy coupled to electron diffraction spectroscopy

Streptococcus sobrinus and Streptococcus mutans
A 24 h immersion confirmed bio-corrosion of the alloy by S.mutans through the dissolution of Ni.

DISCUSSION
Microbial Corrosion of metal is induced by activities of microorganisms like bacteria, fungi, and algae (Wilson et al., 1997;Daubert et al., 2018). The bacteria more commonly attributed to corrosion are SRB, SOB, iron-oxidizing/ reducing bacteria, manganese-oxidizing bacteria, Pseudomonas, bacteria secreting organic acids, and slime. Among the fungi, Cladosporium, Aspergillus, Penicillium, and Paecilomyces (Iverson, 1987), and Candida albicans  are associated with metallic alloy corrosion. Bluegreen algae and a species of red algae (Graciollasia sp.) are the algae associated with corrosion (Iverson, 1987). In the present article, the published literature was reviewed to assess the association between oral microbes and corrosion in intra-oral dental materials. It was observed that various species like Streptococcus, Actinomyces, Veilonella, SRB, SOB, were reported to cause corrosion intraorally. There can be two categories of microbial corrosion based on the involvement of oxygen, anaerobic, and aerobic corrosion. SRB is a classic example of anaerobic corrosion while SOB is a prime example of aerobic corrosion. The basic process of corrosion involves a flow of electricity between certain areas of a metal surface through a solution that can conduct an electric current. Organisms like SOB secrete organic acids as part of their fermentation process which in turn stimulates anodic reactions. Sulphuric acid produced by SOB reduces the pH which in turn favors the growth of iron and manganeseoxidizing bacteria. These microbes oxidize manganese and iron metal alloys and cause their corrosion . Pavlic et al. (2019), Sridhar et al. (2016, and Vaidyanathan et al. (1991) reported that a difference in pH could have contributed to the microbial corrosion. Literature suggests that the lowering pH, although may not corrode as the pH does not reach the depassivation point, it is plausible that it may favor the process (Nash and Kelly, 1993;Schiff et al., 2002). Mabilleau et al. (2006) suggested that S.mitis releases lactic acid in the microenvironment and it is likely that this compound is the main candidate to explain Ti corrosion. Some organisms stimulate cathodic reactions by consuming hydrogen. Sulfate-reducing bacteria (SRB) consume hydrogen through hydrogenase enzymes thereby depolarizing the cathode enhancing the process of corrosion . SRB also utilize lactate produced by other bacteria in the biofilm as a carbon source and reduce sulfate to sulfide. Sulfide combines with iron in SUS alloys to form ferrous sulfide as the corrosion product. Cwalina et al. (2017) found that both groups of bacteria of sulfur cycle, SRB, and SOB colonize NiTi and Ti alloys, with a lower pH favoring the growth of SRB and causing further corrosion. Both SRB and SOB are capable of corroding NiTi and Ti alloys even though Kameda et al. (2014) found a higher degree of corrosion in SUS and none in Ti. This in turn could be because Ti is more resistant to corrosion by electric current.
Corrosion cells also occur when two areas are in contact with different concentrations of the same solution, like a difference in concentration of oxygen. The less-aerated zone acts as an anode, which undergoes corrosion. One of the factors causing such oxygenation difference is the heterogeneous layer of a biofilm with bacteria like Streptococcus mutans which use oxygen and create a difference in degrees of oxygen concentration based on their presence or absence in the biofilm (Alasvand Zarasvand and Rai, 2014). This is the main mechanism behind the corrosion of S.mutans. Fukushima et al. (2014) also suggested a similar mechanism in their study. Actinomyces viscosus consumes oxygen and shifts the anodic curve toward more negative potentials causing corrosion of metals . In addition to other reasons, Díaz et al. (2018) has suggested that surface roughness promotes the corrosion of the Ti surface by S.mutans by creating retentive areas for the bacteria.
There were few contrary findings regarding microbial corrosion. Lu et al. (2017) stated that S. mutans formed a biofilm on the metal surface which enhances corrosion resistance by creating physical barriers that prevented oxygen interactions with the metal surfaces. Lucchetti et al. (2015) too found no significant effect of bacteria like Eikenella corrodens on corrosion of metal alloys. A study by Maruthamuthu et al. (2005) has shown that passivity and corrosion resistance of some SUS and NiTi was improved by bacteria whereas some SUS was shown to decrease. In a study by Liu et al. (2018) found that rapid electrochemical anodization treatment used on Ti2448 alloys increased their biocorrosion resistance. Regarding the prevention against microbial corrosion, Liu et al. (2018) suggested that a new beta-type Ti alloy with a hybrid oxide layer produced by the electrochemical anodization treatment provided better protection against corrosion by microorganisms by lowering the anodic and cathodic current densities. Jorand et al. (2015) showed that the SRB is resistant to ampicillin therapy which might sound that fighting corrosion against these organisms might be difficult. Microbial corrosion needs higher attention in dentistry as more evidence is gathered regarding their role in inducing intra-oral corrosion of alloys. The present systematic review provides insight into the various microorganisms implicated in causing corrosion of intraoral metallic alloy-based dental appliances. Also, the various mechanisms for a microbe induced metallic alloy corrosion are elaborated. Out of the 25 articles reviewed, 23 articles suggested that microorganisms are capable of causing corrosion while 2 articles Lu et al., 2017) suggested that they protect against corrosion and one suggested no significant effect .
Although all the 25 studies had assessed the role of microorganisms in corrosion of dental appliance, most were in-vitro studies simulating the intra-oral conditions. Also, there were several variables including methodology used to assess the corrosion, the research design (in-vitro/in-vivo microenvironment) employed, the microbe and the metal/alloys assessed which led to large-scale heterogeneity in the collected data. In addition, in studies like Pozhitkov et al., the results did not specify the microorganisms responsible for the corrosion . Given the significant number of variables in the included studies and the lack of specificity in reporting the the causative microbe, a quantitative analysis was not possible.

CONCLUSION
The review identified several microorganisms to be closely associated with corrosion of intraoral metallic alloy-based dental appliance. Despite the association, it is vital to acknowledge that most of the included studies were based on in-vitro models. Thus, large-scale multi-center prospective clinical studies with a homogenous research design are required to validate the findings of the present systematic review.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.