Peer Review History

Original SubmissionJanuary 28, 2022
Decision Letter - Amal Al-Bakri, Editor

PONE-D-22-02846Soluble chitosan derivative prevents wound infections and promotes wound healing in a novel MRSA- infected porcine partial- thickness burn wound model.PLOS ONE

Dear Dr. Rubin, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Amal Al-Bakri

Academic Editor

PLOS ONE

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[Note: HTML markup is below. Please do not edit.]

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: No

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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: Yes

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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: No

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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: The paper by Francesco M. Egro et al descibes the effect of soluble chitosan derivative on wound infections and wound healing in a burn wound model. Overall the experimental design is relevant and adeqatelly described, and idea is publication-worth.

There are some questions which should be rized before the consideration for acceptance.

The main question is regarding the characteristic of Wound Cleanser and Catasyn Advanced Technology Wound Hydrogel. Although the reviewer realize that the exact formulation can be closed by patent, some general information should be provided, like the main active compound, in what solution, the molecular weight of chitosan etc. Without this information the results cannot be proven and scientific value of the work is low.

The introduction should be improved by addition of references to works showing the positive effect of chitosan on infected wounds healing, and anti-biofilm activity. A simple search in google scholar gave many works close to this paper. Please site them, may be, excluding those where silver was used as its negative effect is postulated in introduction: https://scholar.google.com/scholar?q=chitosan+antibiofilm+wound+healing&hl=en&as_sdt=0

line 120 add reference to CV-staining protocol

Materials and methods - please give references to similar works if possible, especially in experiments with animals.

244-250. Please add a short explanation why different treatment time was chosen for the rinse and gel.

Fig 3 - It would be worth to add a panel with images of wounds. If these data were obtained form those images which are shown on Fig 5 - please put them together

Reviewer #2: Dear authors,

Thank you for submitting your manuscript. However, I am returning it to you without further review in order not to delay its eventual publication. Therefore, I do not think that the manuscript is suitable to the journal and rejected due to below-following points:

1. The abstract should be rewritten to focus on the aim of this study. This study does not show the main problem to be solved.

2. The novelty of this study must be highlighted. MRSA-infected porcine PTBW model and materials prepared from chitosan derivative were researched popularly and applied for many medicines applications.

3. In the line 341 and 342, the authors said, “the model was designed to reduce cost”. authors should explain more clearly. How does the model reduce cost from this study?

4. Line 347 and 348, the authors said, “this model can be used to save time and reduce animal resources”. Another animal resources will be chosen for different purposes.

5. The figures in the manuscript are not clear and the quality of images should be improved. Furthermore, figure S1 is not clear to read.

6. Language needs substantial improvement.

7. There are many spelling mistakes in the manuscript. Authors should replace “was” word by “were” word in line 119; “scars were inferior” by “scars was inferior” line 291, “treatment lead to” by “treatment led to” in line 303; “dressing change” by “dressing changes” in line 312; “bacteria present in” by “bacteria presents in” in line 354.

Thank you, once again, for submitting the manuscript.

Dr. Thi-Hiep NGUYEN

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Reviewer #1: No

Reviewer #2: No

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Attachments
Attachment
Submitted filename: Comments and suggestions for Authors - PONE-D-22-02846.docx
Revision 1

Dear Editor,

Thank you for your supportive comments and those of the reviewers. We are grateful for the kind and helpful review that supported the clarification of specific points in our manuscript. We have carefully considered the reviewer’s comments and have addressed each one specified below.

Reviewer #1

1. The main question is regarding the characteristic of Wound Cleanser and Catasyn Advanced Technology Wound Hydrogel. Although the reviewer realize that the exact formulation can be closed by patent, some general information should be provided, like the main active compound, in what solution, the molecular weight of chitosan etc. Without this information the results cannot be proven and scientific value of the work is low.

Lines118-125- Additional information on Wound Cleanser and Catasyn Advanced Technology Wound Hydrogel have been included.

2. The introduction should be improved by addition of references to works showing the positive effect of chitosan on infected wounds healing, and anti-biofilm activity. A simple search in google scholar gave many works close to this paper. Please site them, may be, excluding those where silver was used as its negative effect is postulated in introduction: https://scholar.google.com/scholar?q=chitosan+antibiofilm+wound+healing&hl=en&as_sdt=0

Introduction has been revised and additional references have been included throughout the paper- Lines 98, 102, 107, 108, 138, 367, F372.

3. line 120 add reference to CV-staining protocol

Reference has been added.

4. Materials and methods - please give references to similar works, if possible, especially in experiments with animals.

Prior studies demonstrating the benefit of chitosan were discussed in the introduction. “Fu et al showed that chitosan polymers have bactericidal effect against Staphylococcus aureus by binding to the teichoic acids found in the bacterial cell wall (20, 21). In addition to the bactericidal activity chitosan has been observed to accelerate the wound healing process by stimulating inflammatory cells, macrophages, and fibroblasts, hence boosting the inflammatory phase (22). However, at physiological pH, the applications of chitosan are limited due to its poor solubility and limited positive charge (18).”

Our study is the first to our knowledge assessing the impact of chitosan on burn wound healing. The following has been added to the discussion on line 359-360 “Furthermore, no study to our knowledge has determined the impact of chitosan on burn wound healing”.

5. 244-250. Please add a short explanation why different treatment time was chosen for the rinse and gel.

The difference in the treatment times in Figure 2A and 2B reflects the earliest point at which there was a statistically significant reduction of bacteria within the MRSA biofilms. This point was achieved at 1 minute and 10 minutes when treated with wound rinse and wound gel, respectively

6. Fig 3 - It would be worth to add a panel with images of wounds. If these data were obtained from those images which are shown on Fig 5 - please put them together.

Reviewer #2

1. The abstract should be rewritten to focus on the aim of this study. This study does not show the main problem to be solved.

Abstract has been revised focusing on the problem to be solved.

2. The novelty of this study must be highlighted. MRSA-infected porcine PTBW model and materials prepared from chitosan derivative were researched popularly and applied for many medicines applications.

The novelty of this study has been highlighted in lines 357-358, 362-364, 376-380.

3. In the line 341 and 342, the authors said, “the model was designed to reduce cost”. authors should explain more clearly. How does the model reduce cost from this study?

More clarity around this has been provided in lines 370-374.

4. Line 347 and 348, the authors said, “this model can be used to save time and reduce animal resources”. Another animal resources will be chosen for different purposes.

More clarity around this has been provided in lines 370-374.

5. The figures in the manuscript are not clear and the quality of images should be improved. Furthermore, figure S1 is not clear to read.

We are including high quality images. S1 was removed due to low quality. S2 renamed to S1, S3 renamed to S2. The manuscript has been updated.

6. Language needs substantial improvement.

Revisions have been made throughout the paper to improve the language.

7. There are many spelling mistakes in the manuscript. Authors should replace “was” word by “were” word in line 119; “scars were inferior” by “scars was inferior” line 291, “treatment lead to” by “treatment led to” in line 303; “dressing change” by “dressing changes” in line 312; “bacteria present in” by “bacteria presents in” in line 354.

Minor edits and grammatical revisions have been made throughout the paper.

Lines 1, 18, 26, 27, 31, 32,40, 48, 51, 55, 56, 59, 61, 89, 92, 94, 96- 98, 119, 147, 161, 181, 187, 207, 263, 291, 303, 308, 312, 323-326, 353, 358, 361, 371, 372, 376-378, 399-406, 408, 427- 428, 434-435, 440.

Decision Letter - Amal Al-Bakri, Editor

Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA- infected porcine partial- thickness burn wound model.

PONE-D-22-02846R1

Dear Dr. RUBIN,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Amal Al-Bakri

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

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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

**********

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

Reviewer #1: Yes

**********

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

**********

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

**********

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: (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

**********

Formally Accepted
Acceptance Letter - Amal Al-Bakri, Editor

PONE-D-22-02846R1

Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model.

Dear Dr. Rubin:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Amal Al-Bakri

Academic Editor

PLOS ONE

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