PONE-D-23-29572Gait analysis: an effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applicationsPLOS ONE

Dear Dr. Blázquez-Carmona,

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Additional Editor Comments:

The authors need to feedback some small questions to the reviewers.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This work evaluates the potential clinical use of gait analysis for the mechanical assessment of a tissue engineering regeneration as an alternative to the traditional and hardly conclusive manual or radiological follow-up. Nevertheless, there are areas that could benefit from refinement in order to enhance the overall clarity and precision of the manuscript.

Introduction:

Your introduction nicely emphasizes the role of tissue engineering in addressing critical-size bone defects. However, it would be great if you could clearly spell out how your study brings something new to the table in this field.

Line96-112

The gait analysis is well-established. However, you could briefly highlight why gait analysis is a promising avenue for monitoring bone regeneration, especially in weight-bearing critical-sized defects.

Materials and Methods:

The reasoning behind selecting sheep as your animal model and a 15mm metatarsal defect as a critical-size bone defect needs more thorough explanation. Additionally, delving into the specifics of why you chose the particular bioceramic scaffold and external fixator would significantly enhance the manuscript. Providing more 3D-printing details on these decisions will enrich the comprehensibility of your research.

Line152-154

Clarify the rationale behind the specific modifications made to the scaffold design for stability and regenerative response. Additionally, specify the reasons for selecting a 45 vol% hydroxyapatite slurry for the 3D-printing process and the significance of the resulting microarchitecture parameters.

Line202

While the gait analysis section is detailed, consider briefly explaining the rationale behind choosing the specific gait parameters analyzed (GRF peak, GRF mean, tc, Imp) and their relevance to assessing the bone regeneration process.

Line248

Elaborate on the frequency and specific aspects evaluated in the periodic X-rays. How did the X-ray observations correlate with the gait analysis findings, if at all?

Results

Enhance the clarity of the results presentation by including specific numerical values for changes in gait parameters. This will assist readers in comprehending the magnitude of the observed alterations more effectively.

Reviewer #2: This manuscript entitled “Gait analysis: an effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications,” evaluates the potential clinical use of gait analysis for the mechanical assessment of tissue engineering regeneration. The authors demonstrated that gait analysis is an effective, low-cost tool by conducting gait tests after metatarsal replacement in sheep. Here below are specific comments:

1. In the Introduction, the logic needs to be strengthened regarding the role of eliciting gait analysis in evaluating recovery after scaffolding treatment.

2. Lines 96-98: “As another option, gait analysis has been used to follow up on kinematics…”, the reviewer agrees with this as gait analysis has become increasingly important in a variety of clinical assessments. perhaps the authors can refer to below research literature to further verify the opinion: (https://doi.org/10.1016/j.gaitpost.2023.10.019; https://doi.org/10.1038/s41598-022-07054-1 ).

3. Why were sheep chosen as subjects?

4. How is the gait phase determined? The gait of a sheep is different from that of a human, and this affects the trend of the ground reaction forces captured on the force plates.

5. Line 237: Please refer to the relevant studies.

6. Lines 244-245: For the description of linear regression models, please add the more detailed information (https://doi.org/10.1016/j.cmpb.2023.107761). For example, how to interpret the correlation coefficients, such as what is a high correlation and what is a low correlation.

7. The results section is best broken down into smaller points to expand on, which will make the overall logic and content clearer.

8. The clarity of the pictures could be improved.

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Reviewer #1: No

Reviewer #2: No

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Gait analysis: an effective tool to mechanically monitor the bone regeneration of critical-sized defects in tissue engineering applications

PONE-D-23-29572R1

Dear Dr. Blázquez-Carmona,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Yaodong Gu

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Well done!

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you very much for submitting your article. After careful review, I'm pleased to inform you that your article has been thoroughly examined and found to be without any issues. Thank you for your hard work and excellent contribution

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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