Titanium Nitride Plating Reduces Nickel Ion Release from Orthodontic Wire

Round 1

Reviewer 1 Report

18^th September 2021

Review Manuscript Paper # applsci-1390812 entitled "Titanium nitride plating reduces nickel ion release from orthodontic wire”

 

The present research result on new features for plating of orthodontic wire with titanium nitride (TiN)which may be helpful for inhibit the leaching of metal ions from the wire on immersion in acid is an interesting research. However, the authors should address a few minor points.

 

1. The background of the use some acid solution in the paper is lacking since in the discussion it is mentioned related to some systemic diseases such as GERD
2. How acid human oral cavity can be affected by the gastrointestinal acid? Is there any records/references the maximum acid in which can be accepted by the oral cavity? Information about the pH of immersion solution is also lacking.
3. Figures 2 and methods for DMG test, it was mentioned that the strength of the colour reaction on the cotton swab was then evaluated visually and scored with numbers. Is the scoring manually decided by the researcher and how many examiner did the scoring? Would be preferable if there is reference to support the methods.
4. In the methods is also lacking the information how long the wires are immersed in the solution.
5. The result in table 1, for the result of metal ion release particularly Nickel in NiTi and SS TiN coated wire immersed in Hydrochloric acid are indeed less than uncoated but still those are showing high release of ion. What would the author suggested about this result? Are those result dangerous for people who are having allergy? This discussion point is still lacking.
6. In the Figure 1C with the Nickel release graph in Lactic acid, showed high Standard deviation. What would the author suggest about the result? Why the variation is high in the result. Likewise in some of the graphs as well such as in 1a, 1b, 1c.
7. Advantages of the TiN coated technique and Conclusion: Despite claimed as an effective technique, it requires more test such as how long the TiN can stay to have a good mechanical feature to the wires. The possible implications of it (mainly high cost treatment) must be considered. And also how is the biocompatibility of the coated wires?

 

This discussion point is lacking and need to be added in the discussion.

Comments for author File: Comments.docx

Author Response

Reviewer 1

• 1. The background of the use some acid solution in the paper is lacking since in the discussion it is mentioned related to some systemic diseases such as GERD

 

Response: Additional explanations have been added to the text along with additional references (line 51 – 60, and line 62).The content of the sentence in line 258 was duplicated because the relevant section was revised, so a part of the sentence in line 258 was deleted.

 

Revision:

We described the mechanical and frictional properties of TiN-coated wires previously [17], but the details of corrosion resistance have yet to be elucidated. We focused on two acids as potential sources of metal ion leaching from orthodontic wires in the oral cavity. First, as fixed orthodontic appliances induce the retention of bacterial plaque, leading to an increase in level of caries-inducing bacteria in the oral cavity, such as Lactobacillus spp. and Streptococcus mutans [18], and bacteria corrode orthodontic appliances [19], we focused on lactic acid which is their main metabolite that causes low pH [20]. We also focused on gastric acid, mainly hydrochloric acid (HCl), which enters the oral cavity due to gastroesophageal reflux disease (GERD), which has a high incidence of 10% – 20% in adults [21]. In addition to acid erosion of teeth and dissolution of dental restorations [22], gastric acid has been reported to be involved in the elution of metal ions from orthodontic wires [23].

In the present study, we evaluated the corrosion resistance of TiN-plated stainless steel (SS) and nickel titanium (NiTi) orthodontic arch wire immersed in acids by measuring the concentrations of released metal ions, by stereomicroscopic and scanning electron microscopic observation of the wire surface, and by surface roughness measurement.

 

• 2-1. How acid human oral cavity can be affected by the gastrointestinal acid?

 

Response: Additional explanations have been added to the text along with additional references in the Introduction section (line 58).

 

Revision:

In addition to acid erosion of teeth and dissolution of dental restorations [22], gastric acid has been reported to be involved in the elution of metal ions from orthodontic wires [23].

 

• 2-2. Is there any records/references the maximum acid in which can be accepted by the oral cavity?

 

Response: We were unable to find any reports regarding the maximum acidity that can be tolerated by the human oral cavity. However, acute toxicity values of HCl and lactic acid in animals are listed on the supplier’s safety data sheet. For HCl, the LD50 (oral) is 238 mg/kg (rat), LD50 (dermal) is 5010 mg/kg (rabbit), and LC50 (inhalation) is 1411 ppm (rat, 4 h). For lactic acid, the LD50 (oral) is 3730 mg/kg (rat), LD50 (dermal) is 2000 mg/kg (rabbit), and LC50 (inhalation) is 7.94 mg/L (rat, 4 h).

 

• 2-3. Information about the pH of immersion solution is also lacking.

 

Response: The pH of HCl was -1.1 and that of lactic acid was 1.2. This information has been added to lines 82 – 83 in the revised manuscript.

 

Revision:

2.2. Metal ion release testing

Orthodontic wire samples consisting of uncoated SS wire, TiN-coated SS wire, uncoated NiTi wire, and TiN-coated NiTi wire were separately immersed in plastic dishes (untreated 60 × 15 mm dishes; Falcon, Tewksbury, MA, USA) containing 10 mL of physiological saline, sterile water, 35% HCl (pH -1.1) (Wako Pure Chemical Industries, Ltd., Osaka, Japan), and 88% lactic acid (pH 1.2) (Wako Pure Chemical Industries, Ltd., Osaka, Japan). The dishes were placed in an incubator at 37°C for 30 minutes, and the concentrations of Cr, manganese (Mn), iron (Fe), and Ni ions released from the SS wires and of Ni and Ti ions released from the Ni-Ti wires into the solutions were measured by triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS) (ICP-QQQ-Agilent 8800; Agilent Technologies, Santa Clara, CA, USA). The concentrations of metal ions are shown as the mean ± SD of four replicates for each sample.

 

• 3. Figures 2 and methods for DMG test, it was mentioned that the strength of the colour reaction on the cotton swab was then evaluated visually and scored with numbers. Is the scoring manually decided by the researcher and how many examiner did the scoring? Would be preferable if there is reference to support the methods.

 

Response: The method used in this study was based on a previous study [Nakao et al Orthod Wave 2002] and was performed by the same examiner. This has been added in the revised manuscript (lines 93 and 98).

 

Revision:

2.3. DMG tests

The dimethylglyoxime (DMG) test was performed to detect the leaching of Ni from the surface of orthodontic wires immersed in physiological saline, sterile water, 35% HCl, and 88% lactic acid at 37°C for 30 minutes. As described previously [24], two drops of 1% DMG in absolute ethanol and two drops of 10% ammonium hydroxide were added to a cotton swab, which was then rubbed on the sample for 30 s. The strength of the color reaction on the cotton swab was then evaluated visually; the development of a red color was considered a positive reaction indicating the release of Ni from the wire surface. For positive reactions, points were allocated according to the following criteria: dark red, 3 points; red, 2 points; pink, 1 point; and colorless, 0 points. All tests were performed in triplicate by the same operator. The values for all tests are shown as the mean ± SD of three replicates for each sample.

 

• 4.In the methods is also lacking the information how long the wires are immersed in the solution.

 

Response: Information on the immersion times of the wires in the solution has been added in the revised manuscript (line 232).

 

Revision:

Preliminary experiments showed that the peeling of TiN coating gradually became noticeable under the stereomicroscope when immersed in HCl for more than 30 min, so the immersion time was set to 30 min in this study.

 

• 5. The result in table 1, for the result of metal ion release particularly Nickel in NiTi and SS TiN coated wire immersed in Hydrochloric acid are indeed less than uncoated but still those are showing high release of ion. What would the author suggested about this result? Are those result dangerous for people who are having allergy? This discussion point is still lacking.

 

Response: As noted by the reviewer, we used a high concentration of HCl, which resulted in a large amount of elution. A discussion of these points with references has been added in the revised manuscript (lines 213 – 225).

 

Revision:

The amount of metal ions eluted from the TiN-coated SS and NiTi wire and the variations in the data were considered to be greater because of the high concentration of HCl used in this experiment. As the HCl derived from GERD has a lower concentration than that used in this study [23] and the immersion time in GERD-derived HCl is likely to be < 30 min in the oral cavity, the amount of elution is expected to be much smaller than in this experiment. However, as the threshold for Ni allergy is 1.5 μg [28], and there is a risk of onset of metal allergy when exposed to very small amounts of the metal, further experiments are required to examine the use of HCl at a concentration closer to that likely to be present in the oral cavity. Furthermore, the amount of Ni ion elution from uncoated SS wire immersed in lactic acid showed a high standard deviation. The immersion time of 30 min in lactic acid is considered to be the starting point of erosion for the SS wire used in this experiment. In some samples, the amount of Ni ion elution was small because dissolution had only just begun, and this may have resulted in the high degree of variation in the data.

 

• 6.In the Figure 1C with the Nickel release graph in Lactic acid, showed high Standard deviation. What would the author suggest about the result? Why the variation is high in the result. Likewise in some of the graphs as well such as in 1a, 1b, 1c.

 

Response: A discussion and references regarding the variation in the results shown in Fig. 1 a – c in the revised manuscript (lines 213 – 225).

 

Revision:

The amount of metal ions eluted from the TiN-coated SS and NiTi wire and the variations in the data were considered to be greater because of the high concentration of HCl used in this experiment. As the HCl derived from GERD has a lower concentration than that used in this study [23] and the immersion time in GERD-derived HCl is likely to be < 30 min in the oral cavity, the amount of elution is expected to be much smaller than in this experiment. However, as the threshold for Ni allergy is 1.5 μg [28], and there is a risk of onset of metal allergy when exposed to very small amounts of the metal, further experiments are required to examine the use of HCl at a concentration closer to that likely to be present in the oral cavity. Furthermore, the amount of Ni ion elution from uncoated SS wire immersed in lactic acid showed a high standard deviation. The immersion time of 30 min in lactic acid is considered to be the starting point of erosion for the SS wire used in this experiment. In some samples, the amount of Ni ion elution was small because dissolution had only just begun, and this may have resulted in the high degree of variation in the data.

 

• 7.Advantages of the TiN coated technique and Conclusion: Despite claimed as an effective technique, it requires more test such as how long the TiN can stay to have a good mechanical feature to the wires. The possible implications of it (mainly high cost treatment) must be considered. And also how is the biocompatibility of the coated wires?

 

Response: This has been added as an issue for future studies in the revised manuscript (line 267 – 274).

 

Revision:

The following issues should be considered in future experiments. First, it is necessary to examine how long the TiN coating can be maintained in good condition in the oral cavity during orthodontic treatment. Second, the TiN coating is expensive, so cost reduction must be considered for clinical use. We plan to reduce the cost by coating as many wires as possible at once. Although TiN coating has excellent biocompatibility, as demonstrated previously in a device for atrial septal defect closure [14], it will be necessary to study its biocompatibility in the oral cavity where it will be exposed to various chemical substances in food and drink as well as saliva.

Reviewer 2 Report

Arata Ito et al. reported a very interesting article based on the coating of TiN on orthodontic materials to control metal leaching. It is an important requirement in the field of orthodontic treatment of patients with metal allergies. The aim and detailing of the study were well appreciated. Also, the manuscript was well written and investigated with proper experiments. Hence, the present form of the manuscript can be accepted for publication after minor revision.

Minor comments;

Did the authors confirm the thickness of TiN coating layer by SEM?

Authors can include a little description of choosing the HCl and lactic acid in this metal leaching process in the introduction part.

Please include final conclusion or summary of the work at the end of the discussion section.

Author Response

Reviewer 2

• 1.Did the authors confirm the thickness of TiN coating layer by SEM?

 

Response: We measured the thickness of the TiN coating according to a previous study by our group [17]. This information and appropriate reference have been added in the revised manuscript (line 75).

 

Revision:

The thickness of the TiN coating was measured as described previously [17].

 

• 2.Authors can include a little description of choosing the HCl and lactic acid in this metal leaching process in the introduction part.

 

Response: This has been described in the text and appropriate references have been added in the revised manuscript (lines 51 – 60, and line 62).

 

Revision:

We described the mechanical and frictional properties of TiN-coated wires previously [17], but the details of corrosion resistance have yet to be elucidated. We focused on two acids as potential sources of metal ion leaching from orthodontic wires in the oral cavity. First, as fixed orthodontic appliances induce the retention of bacterial plaque, leading to an increase in level of caries-inducing bacteria in the oral cavity, such as Lactobacillus spp. and Streptococcus mutans [18], and bacteria corrode orthodontic appliances [19], we focused on lactic acid which is their main metabolite that causes low pH [20]. We also focused on gastric acid, mainly hydrochloric acid (HCl), which enters the oral cavity due to gastroesophageal reflux disease (GERD), which has a high incidence of 10% – 20% in adults [21]. In addition to acid erosion of teeth and dissolution of dental restorations [22], gastric acid has been reported to be involved in the elution of metal ions from orthodontic wires [23].

In the present study, we evaluated the corrosion resistance of TiN-plated stainless steel (SS) and nickel titanium (NiTi) orthodontic arch wire immersed in acids by measuring the concentrations of released metal ions, by stereomicroscopic and scanning electron microscopic observation of the wire surface, and by surface roughness measurement.

 

• 3. Please include final conclusion or summary of the work at the end of the discussion section.

 

Response: The sentence containing the conclusion at the end of the fifth paragraph has been moved to the Conclusion section and one more sentence has been added (line 276).

 

Revision:

5. Conclusion

TiN plating of orthodontic wires can inhibit acid-mediated corrosion, and thus reduce the elution of Ni ions from the wire surface. These results suggest that TiN plating may be useful for orthodontic treatment of patients with metal allergy. In addition, TiN plating has potential for use in other dental applications, such as coating the metal parts of removable dentures and for wires to splint the teeth after orthodontic treatment.

Reviewer 3 Report

The paper entitled “Titanium nitride plating reduces nickel ion release from orthodontic wire” aimed to examine whether plating of orthodontic wire with titanium nitride (TiN) could inhibit the leaching of metal ions from the wire on immersion in acid.

 

The paper is well written and conducted with appropriate methodology and reported details, sufficient to reproduce the experiments. 

 

The introduction is complete, concise and exhaustive, as well as the M&M section.

 

However,] some points need to be revised :

1. Concerning “2.3. DMG tests ”, I suggest authors, if possible, add further details on the scale of red and the way they indicate them: are they subjectively chosen? (e.g., “Strong read” means darker or more extended painted cotton? And so on.. ) Please, specify in the text.

The results have been reported with clarity, interesting in presentation, including the pictures and the graphs. 

As reported in the text, a better brief explanatory legend in Figures 3 and 4, should be preferred.

The discussion also includes the conclusion. This section is well written as the whole manuscript. The potential use of Titanium nitride plating in other dental applications should be cited, such as for coating the metal parts of removable dentures and for wires splinting the teeth after orthodontics treatments. 

 

I appreciated the table of abbreviations and the quality of the work. I hope it could encourage further development in clinical dental fields. 

Author Response

Reviewer 3

• 1.Concerning “2.3. DMG tests ”, I suggest authors, if possible, add further details on the scale of red and the way they indicate them: are they subjectively chosen? (e.g., “Strong read” means darker or more extended painted cotton? And so on.. ) Please, specify in the text.

 

Response: A detailed explanation of the experimental method has been added in the revised manuscript (line 98).

 

Revision:

For positive reactions, points were allocated according to the following criteria: dark red, 3 points; red, 2 points; pink, 1 point; and colorless, 0 points.

 

• 2. As reported in the text, a better brief explanatory legend in Figures 3 and 4, should be preferred.

 

Response: The legends for Figures 3 and 4 have been shortened.

 

Revision:

Figure 3. Stereomicrographs of orthodontic wire immersed in HCl or lactic acid for 30 minutes: (a) TiN-coated SS wire; (b) Uncoated SS wire; (c) TiN-coated NiTi wire; (d) Uncoated NiTi wire.

 

Figure 4. Scanning electron micrographs of orthodontic arch wire immersed in HCl or lactic acid for 30 minutes (×200): (a) TiN-coated SS wire; (b) Uncoated SS wire; (c) TiN-coated NiTi wire; (d) Uncoated NiTi wire. (×1000): (e) TiN-coated SS wire; (f) Uncoated SS wire; (g) TiN-coated NiTi wire; (h) Uncoated NiTi wire.

 

• 3. The discussion also includes the conclusion. This section is well written as the whole manuscript. The potential use of Titanium nitride plating in other dental applications should be cited, such as for coating the metal parts of removable dentures and for wires splinting the teeth after orthodontics treatments.

 

Response: This has been added to line 279 in the revised manuscript.

 

Revision:

In addition, TiN plating has potential for use in other dental applications, such as coating the metal parts of removable dentures and for wires to splint the teeth after orthodontic treatment.