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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 6  |  Page : 539-548

Perspective on metal leachables from orthodontic appliances: A scoping review


Cluster of Craniofacial and Biomaterial Sciences, Advanced Medical and Dental Institute (IPPT), Universiti Sains Malaysia, Kepala Batas, Pulau Pinang, Malaysia

Date of Submission05-Mar-2021
Date of Decision17-Apr-2021
Date of Acceptance29-Apr-2021
Date of Web Publication30-Nov-2021

Correspondence Address:
Dr. Noor A Ahmad Shafiai
Cluster of Craniofacial and Biomaterial Sciences, Advanced Medical and Dental Institute (IPPT), Universiti Sains Malaysia, 13200 Kepala Batas, Pulau Pinang.
Malaysia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIOH.JIOH_52_21

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  Abstract 

Aim: Metal ion leaching from orthodontic fixed appliances can be retrieved through in vitro, in vivo, and clinical studies and this study aims at reporting the methodology employed in previous studies for assessing metal leachables from orthodontic appliances. Materials and Methods: Available reports from Google Scholar were compiled using PRISMA guidelines from 2009 to 2020, with certain keywords in identifying studies reporting on metal leaching from orthodontic appliances. A total of 1390 studies were identified and after the exclusion of articles, 69 final articles were reviewed. Data such as the types of materials, incubation medium, duration, type of cells, assay, and factors for corrosion were summarized. Results: Metal leachable from orthodontic appliances mostly occurred through a corrosion process caused by internal structural factors (such as metal composition and particle distribution), as well as external factors (such as media composition, pH, and biofilm). The studies involved various methodologies of research in metal ion release and cytotoxicity determination. Conclusion: Nickel was the most common ion investigated, followed by chromium in this study of cytotoxicity of orthodontic appliances during the past 10 years. The trends and needs in wearing orthodontic appliances should receive a different perspective with regards to metal leaching, which may give rise to adverse effects in long-term application.

Keywords: Metal Leaching, Nickel, Orthodontic, Scoping Review


How to cite this article:
Haleem R, Ahmad Shafiai NA, Mohd Noor SN. Perspective on metal leachables from orthodontic appliances: A scoping review. J Int Oral Health 2021;13:539-48

How to cite this URL:
Haleem R, Ahmad Shafiai NA, Mohd Noor SN. Perspective on metal leachables from orthodontic appliances: A scoping review. J Int Oral Health [serial online] 2021 [cited 2022 Jan 27];13:539-48. Available from: https://www.jioh.org/text.asp?2021/13/6/539/331585


  Introduction Top


The primary objective in receiving orthodontic treatment is to develop better oral function in improving speech and mastication, reducing the incidence of trauma from large overjet and consequently easier cleaning of the teeth. Orthodontic treatment has a significant impact on the quality of life, as it improves self-image; specifically, the wearing of fixed orthodontic appliances is an important factor in the behavioral relationship among adolescents, particularly owing to their association with social status.[1] There are many devices for the treatment of orthodontics, which includes removable and functional appliances, but the one that is the most common is the fixed appliance. The appliance is fixed to the teeth, making teeth movement mostly dependent on the operator’s modus operandi, whereas the success of removable and functional appliances is largely dependent on the compliance of patients. The duration of orthodontic treatment can be extended up to two years, determined by the severity of malocclusion. The prolonged treatment with a metal appliance fixed to the teeth in the oral environment raised concerns on the amount of metal ion leaching into the body due to corrosion, as well as the graded degradation of materials by an electrochemical attack.[2]

Fixed appliances in orthodontics include archwires, brackets, and molar bands/tubes, and they are mainly composed of alloys containing chromium (Cr), cobalt (Co), iron (Fe), titanium (Ti), and nickel (Ni). The latter has received the most attention, as it may impose allergic reactions.[3] Metal ion leaching from orthodontic fixed appliances can be retrieved through in vitro, in vivo, and clinical studies. In vitro studies enable the modification of confounding factors that simulate an oral environment, such as pH and temperature changes, biofilm formation, dietary intake, and use of mouthwashes/dentifrices. This, however, will not reflect the actual symbiosis in the oral cavity. In a normal situation, saliva, which is produced in the mouth, is constantly replaced as it flows through the oral cavity system. In vivo and clinical studies, on the other hand, allow for the evaluation of tested devices in natural, functional, and oral environments. However, due to variations in the oral activities of individuals, the interpretation of the results may prove to be difficult. This article aims at reporting the methodology employed in previous studies for assessing metal leachables from orthodontic appliances through a scoping review analysis. The results obtained will provide a new perspective regarding the type of ions commonly released from metallic orthodontic appliances that may have detrimental effects toward health and suggest precautionary measures to orthodontic appliance wearers.


  Materials and Methods Top


The available literature from the Google Scholar was referred using search terms led by Boolean operators “AND” and “OR” with the keywords “cytotoxicity,” “orthodontics,” “genotoxicity,” “in vitro,” “corrosion,” “in vivo,” and “metal release” using a methodological framework fashioned by Arksey and O’Malley,[4] which consisted of five steps, namely (a) identification of the research question, (b) identification of relevant studies, (c) selection of study, (d) data charting, and (e) collating, summarizing, and data reporting.

Identification of research questions

The following are the two research questions that were developed to align with the objective of this study: (a) What are the types of materials, incubation medium, duration, type of cells, and type of assay commonly used during in vitro studies, for assessing metal leaching from orthodontic appliances? (b) What are the types of cells, duration, and methods commonly used during in vivo studies, for assessing metal leaching from orthodontic appliances?

Identification of relevant studies

Relevant studies were identified through eligibility criteria, databases, and a search strategy. The inclusion criteria were articles in the English language, or articles that have been translated into the English language and published between January 1, 2009 and June 30, 2020.

Selection of study

The inclusion criteria were developed through an iterative process, involving two phases of screening. First, a total of 1390 studies were identified through the search study. During the screening process, three reviewers independently assessed the title and abstract of the studies, retrieved from the search strategy, whereby the abstracts were read, analyzed, and selected, based on the eligibility criteria. After the exclusion of duplicate records, review articles, and articles that did not meet the inclusion criteria, 95 articles were identified. The articles were further analyzed by way of an assessment of the final full text article. Articles that were deemed irrelevant, or unrelated to the release of metal ions from orthodontic appliances, were excluded. A total of 69 final articles were reviewed.

Data charting, collating, summarizing, and data reporting

The data obtained from the final full article at the previous step were then extracted and charted. This process provides a summary that complies with the research question and objective of the study. The data extraction includes the name of the author, the year of publication, the title of the article, and information related to the theme of the study. A PRISMA flow diagram, illustrated in [Figure 1], provides an accurate presentation of the scoping review framework, as well as the results.
Figure 1: PRISMA flow diagram of the scoping review framework

Click here to view



  Results Top


The most common ion in the assessment was nickel followed by chromium. Less than 10 papers investigated the leaching of copper, cobalt, iron, manganese, and other elements. The types of samples commonly used were archwires (29 studies), brackets (26 studies), and molar bands (12 studies).

Non-cell culture studies

For in vitro studies, where the internal factors of corrosion were controlled, such as pH and temperature, artificial saliva was mostly used as incubation medium. One study reported the use of Hank’s Balanced Salt Solution[5] and neutral and acidic solution,[6] respectively. Some studies investigated other mediums commonly used during orthodontic treatment, such as different mouthwashes products[7],[8] and dental bleaching gels[9]; distilled deionized water was used as control.[7],[8]

The incubating medium was prepared according to a specific dosage, based on the weight of the samples, which ranged from 100 mg/mL up to 1000 mg/mL. The incubation duration for orthodontic appliances in the incubation medium ranges from 15 min to one day, seven days, one month, and up to 90 days.[2][Table 1] summarizes studies assessing metal ion leachables from orthodontic appliances incubated in medium without exposure toward cells.
Table 1: Types of metal leachable from orthodontic appliances incubated in incubation medium (noncell culture studies)

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Cell culture studies

In assessing the cytotoxicity of orthodontic appliances, human (four studies), animal (six studies), or primary human cell lines (eight studies) were used as experimental replicas [Table 2]. For human and animal cell lines, the types of incubation medium used were artificial saliva, Dulbecco’s minimal essential medium (DMEM), and artificial saliva manipulated with varieties of acidity or fluoride density. In primary human cell lines, most studies took samples from buccal epithelial cells, with one study that collected cells from the inside part of the lip[10] and one that collected gingival fibroblasts.[11] Cell counting and membrane integrity were used as endpoints for the determination of the cytotoxicity test or assay. The MTT tetrazolium-based dye was commonly used to measure the mitochondrial succinate dehydrogenase activity in living cells.[11],[12] Other assays used were the Comet and micronucleus (MN) assays. Four studies utilized the Comet assay for assessing the destruction of DNA in cells, stemming from appliances’ medium extracts. These studies focused on the biocompatibility between the product and the cells.[13],[14],[15],[16] Twelve studies involved real orthodontic patients as subjects, and one study implanted a plate with an equivalent weight of fixed appliances in pigs, to determine the systemic metal ion leaching into the animal body. Patients with fixed upper and lower orthodontic appliances had their saliva collected at different period of times. The longest period detected for salivary collection was nine months after the placement of the fixed appliance and 15 months after the debond procedure. One study collected blood serum, whereas four studies collected scalp hair.
Table 2: Types of metal leachable from orthodontic appliances and their effects toward human cells lines, human primary cells, and animal cell lines (cell culture studies)

Click here to view



  Discussion Top


Ions leaching from orthodontic appliances

Ions leached from orthodontic appliances can be grouped according to the periodic table groupings, which include alkali metal, alkaline earth metal, transition metals, metalloids, post-transition metals, and reactive nonmetals, based on their similar characteristics and chemical properties. Ni and Cr are in the transition metals group and it is not surprising that they are the elements of most concern in the field of orthodontics, as the materials are mostly contained in stainless steel (about 8–12% of Ni and 17–22% of Cr), and more than 50% of Ni are contained in nickel titanium.[8] The combination of materials in one patient’s mouth, which include bracket, archwire, and bands/tube, explains the reasons for cytotoxicity, which is the subject of most research in this area. Ni is found to be at a low concentration in the human body; the elevation of the element can impose serious damage to health and is related to various systemic disorders. Ni is also associated with allergy, where it is affecting 8–18% of the population in European countries.[17] For Cr, a safe daily dose is 0.03–0.13 µg/kg whereas a normal range of 20–30 µg/L in the blood also indicates a low concentration of that ion in the body. The increased exposure to chromium ions in the body can inflict serious illnesses, such as irritation to the airways and allergy to the skin.[18] The International Agency for Research on Cancer (IARC) identified Ni and Cr compounds as elements that can promote carcinogenesis in humans.[19] It was observed that the concentration levels of Ni and Cr in saliva were increased after the placement of orthodontic appliances,[20],[21],[22] but the amount is still below than the recommended dietary intake. The concentration level of other ions in the current investigations also expressed a similar pattern.

Factors contributing to metal leaching from orthodontic appliances

Corrosion is defined as an electrochemical reaction on the metallic surface, leading to a reduction in material properties. In the context of orthodontic appliance corrosion in the oral environment, the emphasis is on two areas: (a) internal corrosive issues stemming from the metal composition and structure of the orthodontic appliance, and (b) external issues associated to the biological surroundings, which includes the pH value, media composition, and strain.[23] Corrosion products can be absorbed into the body and lead to systemic or localized effects. Corrosion stems from the draining of metal ions into a solution, or the progressive dissolution of a surface layer, typically a sulfide or an oxide.

The internal corrosive factors, which contribute toward metal ion leaching from orthodontic appliances, is determined by the type and structure of the material; as well as the alloy composition used for the fabrication of the appliances. Fixed orthodontic appliances with similar kinds of alloys (SS and NiTi alloys), produced by different companies, can differ in alloy composition from one company to another. This can be attributed to differences in production technologies and electrolytic coatings. Different ionic releases were observed from dissimilar types of wires and brackets, as well as from dissimilar types of incubation mediums. The different metal ions released by dissimilar archwire mediums may be attributed to the oxidation treatment, during the fabrication of the archwires.[15] The neutral and acid media solutions used during these studies also play a role in determining the amount of metal ions leached into the incubating medium. The different analytical methods adopted for assessing metal ion leaching resulted in dissimilar sensitivity and detection limits. This situation rendered the comparison between results a rather daunting affair.[24],[25]

Besides the composition of the appliance and its various production technologies, the condition of the functioning archwire may also play a part in the release of metal ions. More Ni ions were released during the engagement of NiTi wires into brackets of crowded teeth, as opposed to unstressed archwires.[26] When the wire of NiTi bends, it creates stress, which instigates destruction to the passive oxide film on the wire, leading to exposure of the active metal surface. On the other hand, when compared between brackets that were new, recycled, or subjected to commercial recycling, no significant differences were reported in the release of Ni.[27]

The external corrosive factors that contribute to metal ion leaching include pH changes, body temperatures, and experimental temperatures adopted in research. Changes in pH within the oral environment significantly influence the release of metal ions from orthodontic appliances.[23],[25],[28],[29],[30] A low pH value reduces the resistance of dental alloys to corrosion, and the acidic oral environment stems from a combination of nutrition, decomposition of diets, biofilm, cell debris, and oral micro flora. During the consumption of food, various acids are formed during the microbial attack on metallic orthodontic appliances. Decalcification of teeth and metallic appliance corrosion are influenced by food debris, biofilm, and the metabolic products of microbes on the tooth surface. Prolonged exposure of the brackets to the oral environment led to the development of pitting corrosion, plastic distortion, gaps, scratches, and debris deposition.[31],[32],[33]

Although it is mandatory for orthodontic patients to practice good oral hygiene, some studies have reported that the fluoride ions in fluoride-containing toothpastes, mouthwashes, and prophylactic gels can have a detrimental effect on the corrosion resistance properties of Ti or Ti alloys. A significant elevation in the release of elemental ions from Ni alloys was detected, with the use of toothpaste.[34],[35] Fluoride ions in artificial saliva reduce the corrosion resistance of the NiTi archwire, especially at a sodium chloride concentration of 0.5%. The orthodontic treatment duration, food intake, salivary flow, and teeth hygiene are other factors influencing the corrosion resistance capacity of orthodontic appliances. The longer an orthodontic appliance remains in the mouth, the greater the likelihood of an increase in the release of metallic ions.[36] Chloride ions in salty food can combine with hydrogen, to produce a corrosion-causing acid. The saliva production capacity and composition in the oral cavity, as well as the act of toothbrushing may influence the extent of oxide layers, removed from the appliance. The removal of these oxide layers can bring about a greater release of metallic ions. One study traced a high amount of Ni ions, collected from the saliva of healthy subjects with fixed orthodontic appliances, to the radiofrequency radiation, emitted from their mobile phones.[37]

Methods of determining cytotoxicity

For human origin cell lines, fibroblast cells from human gingiva[38],[39] and the human osteosarcoma cell line (Saos-2) were harvested, as they are closely positioned to the placement of orthodontic appliances in the oral cavity. As for the nonhuman cell line, mouse fibroblast cells (L929) were frequently used.[40],[41],[42],[43],[44],[45] These cells were exposed to the medium extracts from brackets or archwires or seeded directly on the brackets or archwires.

Saliva[46],[47],[48],[49] and exfoliated oral mucosa cells[50],[51],[52],[53],[54] obtained by scratching the cheek buccal mucosa were frequently used to assess metal leaching originating from orthodontic appliances, as they represent the medium of the oral cavity in which orthodontic appliances are placed. Interestingly, human hair[24],[50],[51] and scalp hair[52] were also used to monitor metal ion leaching from orthodontic appliances. The toxicological biomonitoring was examined by way of a noninvasive matrix analysis, to ascertain the variations in the release of metal ions. The advantages that come with the use of human hair include easy collection, low costs, trouble-free transportation, and undemanding storage. Moreover, hair samples showed no changes in the storage content between collection and analysis time, and they often offer information on the short and long-term exposure to the released metal ions.

Among the testing approach recommended by ISO 10993; ISO 7405 are cell counting and membrane integrity, which are used as endpoints for the cytotoxicity test or assay. The MTT is widely used in research.[11],[12] This assay exploits the ability of the cells to reduce the tetrazolium dye to insoluble formazan.[45] Other assays used were the comet and micronucleus assays. The Comet assay is among the most sensitive and quick assays for the detection of DNA strand breaks. The usage of this assay, which has been on the rise over recent years,[31] is based on the principles governing the monitoring and comprehension of DNA damage.[46] The MN assay, which provides an accurate, fast, and broad-spectrum determination of DNA damage at a chromosome level, comes with limited costs and a minimal testing period.[10],[47],[48]

The in vivo study reflected the real oral environment for determining fixed orthodontic appliances. The study can stretch to a period of up to a year, depending on the malocclusion, and the long-term side effects stemming from exposure to metal ions can be monitored. However, the process would not provide a reliable result, when it comes to changes in the release of metal ions as patients usually attend review appointments every four to six weeks. In such situations, an in vitro study has the advantage with the capacity to frequently and quickly measure the release of metal ions in a matter of hours or days. The disadvantage is in the variety responses of animals and humans; hence, extrapolation may not deliver accurate findings. Nevertheless, animal studies allow for a controlled environment throughout the study period.

It is notable that from these findings, genotoxicity and DNA damage resulting from orthodontic products are rare. However, the long-term effects of metal ion leaching from this appliance are scarce. The limitation of this review is the restriction in searching the articles where only Google Scholar was chosen. It is our recommendation that future work in this area focuses on: (a) identifying the toxic dose for each element, (b) extending the incubation period of samples in the medium, prior to the usage of extracts on cells, and (c) examining the blood/saliva of patients two years after the completion of treatment, to monitor the long-term effects (if any) of cytotoxicity on the human body.


  Conclusion Top


Nickel was the most common ion investigated, followed by chromium in this study of cytotoxicity of orthodontic appliances during the past 10 years. The trends and needs in wearing orthodontic appliances should receive a different perspective with regards to metal leaching, which may give rise to adverse effects in long-term application. Sample selection is crucial for these studies, as it affects the type and amount of metal ion leaching.

Acknowledgements

This review was funded by Short Term Grant, Universiti Sains Malaysia (304/CIPPT/6315227).

Financial support and sponsorship

Short Term Grant, Universiti Sains Malaysia (304/CIPPT/6315227).

Conflicts of interest

The authors declare that there is no conflict of interest.

Authors’ contributions

RH, NAAS, and SNFMH contributed to the design and review of the suitable articles; RH wrote the article with close support from NAAS and SNFMH.

Ethical policy and Institutional Review Board statement

Not applicable.

Patient declaration of consent

Not applicable.

Data availability statement

Data are available upon a valid request to the corresponding author.



[60]

 
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