A New Method for Assessing the Rate of Biodegradation of Magnesium Alloy-Based Products in an In Vivo Experiment

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The work presented in this manuscript is interesting; the authors compared the volume of gas cavities around three screw groups in a rat model, determined by means of MSCT. However, many important details are missing, which undermines the scientific value of the work. The authors may consider the following suggestions and questions.

×          In Abstract, “ a numerical method” may be misleading. “A quantitative method” may be a better expression.

×          In 2.2, what was the exact composition of the magnesium alloy for the screw as well as its processing history? What are the type of the screw, sizes and thread profile features? Was were the compositions of ceramic coating and fluorinated coating? What were the methods used to coat the screws, especially the threaded section? What were the features of these coatings, such as thickness, roughness, bonding strength, etc?

×          In 3.1, the sentence: “the efficiency of CT in determining… the actual values” is not understandable. Do you actually mean “accuracy” instead of efficiency? How were the actual values determined?         

×          In 3.2, the sentence: “the accuracy of gas volume… 70% sensitivity” is not understandable. How can accuracy be measured by sensitivity? (These are two different measures.)

×          In 3.3, the sentence: “It provides accuracy of up to 85%, but the efficiency of….” is incomplete and confusing. Do you mean 85% of the measured value? How was the measured value determined? What is the efficiency of measurements here?

×          It will be great if the authors can insert a scale bar into each of the MSCT images (Figures 2-4).

×          In 3.4, the authors are expected to present the data of the screw volume change with time, which may correlate to the gas volume changes given in Table 2.

×          In Discussion, the authors do not discuss their own findings, for example, the trends of gas cavity volume with implantation time, in comparison with the literature data.  

×          In Discussion, the sentence “Magnesium alloy screws are resistant to corrosion” seems to be an overstatement, unless the authors present the data about the retained screw sizes after 4 week (my comment #8) supports it.

×          The most part of the Discussion section is about the state of the art and may better be moved to the Introduction section (Speaking about…..within the first 24 hours).

×          In Conclusion, the formation coefficient of gaseous hydrogen per 1 mm3 suddenly appears. Actually, this coefficient could be estimated from the CT data if the screw volume changes were determined.

 

 

 

Author Response

Dear Reviewer! Thank you for your time and valuable advice! Responses to your corrections and comments are in the attached file.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

thank you for the opportunity to have a look at your work before publication. The text is nicely and convincingly written. However, some information is missing to compare your results with other papers and to be citable in the future, so please see the comments below.

 

Major comments:

1. I wonder what is new to me or other readers. By including more information about the final geometry of the screws or even during the stages of implant placement, you can add some more useful information to your work. If it is possible, you should at least include the information about the final geometry of the implant, possibly also of the bone. This is because the lifetime of the implants is important and the areas where corrosion or degradation will occur. In my opinion, information on bone remodelling is essential for a specific application as an implant to repair a bone fracture.

2. I too wonder whether gas formation is critical or not. Therefore, I recommend a discussion on this topic. When a new doctor reads this paper, they are not willing to use this type of gas-forming Mg implant. If you convince them that this is not a problem, they are not as sceptical as they would be without an explanation on the subject. In my opinion, these cavities are not really a problem in the long term, but in the initial phase of healing they can affect the healing progress. The composition of the gas may also be of interest. I therefore recommend literature on this topic such as “Fast escape of hydrogen from gas cavities around corroding magnesium implants” (https://doi.org/10.1016/j.actbio.2012.10.008).

3. There is some important information missing to relate your results to other work. From my point of view, the ‘Experimental Design and Surgical Procedure’ needs to be expanded with information about the used Mg alloy with the composition and impurities as well as information about the coating process with parameters and composition of the solution. Geometric information on the screws, such as size or surface area, is also missing so that they can be compared with other works.

4. In 3.1, 3.2 and 3.3, only one source is referenced for each technique, which in my opinion is insufficient for publication. Therefore, I strongly recommend improving the literature review to better support your statements. In the case of [5], there is no information on the application of MRI to gas voids and therefore it is not a support for your conclusions.

 

Minor comments:

1. Line 111: Add the voxel size of your CT set up.

2. Line 121 and 131: Use gas not air

3. Figure 3: Make the illustration bigger or the yellow points and the green boundary bigger.

4. Figure 4: Add scale bars.

5. Line 200: Not Table 1 it is Table 2.

6. Table 2.: I recommend add exchange the table by a diagram.

7. Line 206 and 207: The – is confusing me. I prefer it was like before.

8. Line 222 and 231: Mg2+, OH–, and H2 à The 2+ and - should be superscripted and the 2 of H should be superscripted.

9. Line 241: The statement: “This is because the diffusion of the formed gas in solution is faster 241 than in tissue.” Is for me just correct to some extent, because the gas bubbles will swim up and in a setup with liquid media it is the dominant process of losing H2 from the implant or sample.

10. Line 287: The 3 should be superscripted.

Author Response

Dear Reviewer! Thank you for your time and valuable advice! Responses to your corrections and comments are in the attached file.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

(1)    In Introduction, “numerically assessing the volume…” should be changed into “quantitatively assessing the volume..”

(2)    In 2.2, the details of the coatings (i.e., the ceramic coating and fluoridation-based coating) are still missing, including the compositions of the coatings, coating methods, coating thicknesses, bonding strengths, roughness, etc. Without these details, the reader will not be able to understand the three groups in Results (Table 2 and the text from “After one week….”) and part of Discussion (This study shows that….).

(3)    Table 2 compares the gas cavity volume (group 1) with screw volume (group 2 and group 3), which makes little sense. I think both gas cavity value and screw volume for each of the screw groups should be presented. In addition, asterisk is missing in Table 2.

(4)    The majority of the Discussion from “It is important to note….within the first 24 hours” concerns the state of the art. As such, these sentences should be placed in the Introduction section and the Introduction should be rewritten.

(5)    In Discussion, “Table 1” should be changed to “Table 2”.  

Author Response

Dear reviewer! Thank you for your time in correcting our work.

Responses to your comments are in the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors, 

thank you very much for revising your work. 

You should take a closer look at the revised sections, as a few spaces are missing and the dots are too many or in the wrong place.

If you correct these minor errors, your work is fine for me to accept and publish.

Author Response

Dear reviewer! Thank you for your time in correcting our work.

Responses to your comments are in the attachment

Author Response File: Author Response.pdf

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have removed the coated Mg alloy screws from the manuscript. Now, it concerns the method of assessing the gas cavity volume along with in vivo experiment of Mg alloy screws. The following minor changes can be introduced during the proof-reading stage:

(1)    In Abstract: “a promising material” should be changed into “promising materials”.

(2)    In Introduction, line 57, a raised pH value will suppress the further degradation of Mg while a maintained pH will not reduce the formation of gas cavities.

(3)    In Introduction, line 61, “is” should be changed into “has been”.

(4)    In Introduction, line 103, “monitoring of the condition” is not understandable.