PONE-D-20-16200

Bioactive Silica-Hydroxyapatite coaxial composite scaffold for bone tissue engineering

PLOS ONE

Dear Dr. Reyes-López,

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.

It has been reviewed by experts in the field and we request that you make Major Revision before it is processed further. Please find your manuscript and the review reports below:

Reviewer 1

Some typing errors and grammatical errors present throughout the manuscript. Methodology for in vivo study does not clearly stated the sample size. Objectives not clearly stated both in the abstract and introduction, especially not mention anything about characterization of the material and in vivo study.

Reviewer 2

In this research, investigate the cytotoxic behavior of electrospun SiO2-HA non-woven ceramic membranes. However, some issues regarding present study should be addressed before publication in PLOS ONE. It is recommended that the following be done to complete the article:

1-“Abstract” should be rewritten again by considering better grammar.

2- Generally, using chemical formulas such as ‘SiO2” is not usual in “Keywords”. Therefore, another keyword should be replaced instead of “SiO2”.

3- What does the surface area of SiO2-HA fiber indicate? Please discuss the issue?

4- Results of ATR-FTIR should be mentioned with references. Please examine the issue.

5- Statistical analysis or p-value is required for in vitro and in vivo tests. Please mention the issue in the manuscript.

6- Results of in vitro and in vivo should be expressed in “Conclusion”. “Conclusion” should be rewritten again.

7- To conclude, writing related to manuscript is weak. Please examine and use better grammar for it.

Reviewer & Editor Comments

Q1: In the abstract, you need to focus more on the quantitative information, not qualitative ones.

Q2: In the “Introduction” section, the authors were supposed to clear the answers of the following questions;

a. Which exact problem was supposed to be solved by the present research?

b. Which new achievement(s) was supposed to be obtained by the present research in comparison with the previous reports?

Q3: Title and subtitle of each section require numbering.

Q4:  Please describe the underlying reason behind selection of silica precursor at 10 w/v% and HA sol at 20 w/v% for the composite fibers.

Q5: You stated that " The surface area of the sintered SiO2-HA fibers was 5.77 m2/g, with an

average pore width of 135.87 Å". How did you measure surface area and averages pore width

of the sintered SiO2-HA fibers.

Q6: In the method section, how many times have you repeated the cell culture tests? Have you considered the repeatability of the tests?

Q7: Histogram analysis of SiO2-HA fiber composite to further confirm the average diameter of fiber composite and its distribution.

Q8: What do you mean by "vibrational modes assigned to "...725 cm-1 for P2O74-". There is no such band "P2O74-" in aforesaid wavenumber.

Q9: "vibrational modes of Si-O-Si" should be indicated in the ATR-FTIR analysis". In addition, your statement is not clear "according with IR and XRD the combination of SiO2 an HA does not introduce a differential or partial phase transformation of HA to another tricalcium phosphate".

Q10: I recommended the author to present the value of "crystallinity percentage", and "crystalite size" of HA and SiO2-HA in the table instead of Fig. 5.

Q11: the author should check the value of cell viability of fibroblasts incubated onto thermal-treated SiO2, HA and SiO2-HA. You present high cell viability of fibroblasts regarding SiO2, HA and SiO2-HA, these values should be compared with other study and literature. It is worth noting that you stated that  "SiO2 has a negative effect on certain cell cultures such as endothelial and fibroblast [29, 30]" which has a contradiction with  presented value in the graph (Fig. 6).

Q12: Y axis of Fig. 6 is missing. In addition, "*" sign is missing too inside the graph.

Q13: Table 1 and Table 2 regarding "Regression Analysis for Mixture Process Variable Model of values at 24 h and 48 h" could be presented in the supporting information.

Q14: Fig. 7 and Fig. 8 regarding maximum optimal response should merge together and be presented as Fig. 7a, b.

Q15: For benefit of readers, the schematic illustration regarding schematic demonstration of the interactions between the fibroblasts cell and surface of SiO2-HA fiber composite could be presented.

Q16: In conclusion part, you need to present more quantitative data in order to make it easier and convenient for readers to compare the specimens.

Q17: Moreover, for possible final paper acceptance, it is requested that authors improve the English

presentation, both grammar and style. Authors are strongly advised to have their paper revised for language by a native English or equivalent expert.

Q18: Surprisingly small reference to PLOS ONE in the literature despite the large relevant literature there. This should be improved. There are several important papers in the recent literature

" between 400-4000 cm-1" should change to " between 400-4000 cm-1"

" cells. [27,28]" should change to " cells [27,28]."

"membrane. [28]" should change to "membrane [28]."  

Please submit your revised manuscript by Sep 17 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Hamid Reza Bakhsheshi-Rad

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

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2. Thank you for stating the following financial disclosure:

"no"

At this time, please address the following queries:

1. Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.
2. State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”
3. If any authors received a salary from any of your funders, please state which authors and which funders.
4. If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

3.  In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: No

**********

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: No

Reviewer #2: Yes

**********

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: No

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: Some typing errors and grammatical errors present throughout the manuscript.

Methodology for in vivo study does not clearly stated the sample size.

Objectives not clearly stated both in the abstract and introduction, especially not mention anything about charaterization of the material and in vivo study.

Reviewer #2: Publish after major revision

In this research, investigate the cytotoxic behavior of electrospun SiO2-HA non-woven ceramic membranes. However, some issue regarding present study should be address before publication in PLOS ONE. It is recommended that the following be done to complete the article:

1-“Abstract” should be rewritten again by considering better grammar.

2- Generally, using chemical formula such as ‘SiO2” is not usual in “Keywords”. Therefore, another keyword should be replaced instead of “SiO2”.

3- What does the surface area of SiO2-HA fiber indicate? Please discuss about the issue?

4- Results of ATR-FTIR should be mentioned with references. Please examine the issue.

5- Statistical analysis or p-value is required for in vitro and in vivo tests. Please mention the issue in the manuscript.

6- Results of in vitro and in vivo should be expressed in “Conclusion”. “Conclusion” should be rewritten again.

7- To conclude, writing related to manuscript is weak. Please examine and use better grammar for it.

**********

6. 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

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-16200R1

Bioactive Silica-Hydroxyapatite coaxial composite scaffold for bone tissue engineering

PLOS ONE

Dear Dr. Reyes-López,

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.

However, for sending the decision letter the authors should revise the manuscript to address the comments received from the reviewer, point-by-point and sufficiently described below each comment and then highlight the revised section in the manuscript. All the changes should mark in different colors in the revised manuscript. The response to the reviewers in this form is not acceptable and should be modified according to the aforementioned comments and resubmit the revised manuscript.

Please submit your revised manuscript by Nov 02 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Hamid Reza Bakhsheshi-Rad

Academic Editor

PLOS ONE

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

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-16200R2

Bioactive Silica-Hydroxyapatite coaxial composite scaffold for bone tissue engineering

PLOS ONE

Dear Dr. Reyes-López,

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.

Specific questions and comments are listed as follow:

Q1: As mentioned previously, you stated that "The surface area of the sintered SiO2-HA fibers was 5.77 m2/g, with an average pore width of 135.87 Å". How did you measure the surface area and averages pore width of the sintered SiO2-HA fibers? The procedure should be presented in the materials and methods.

Q2: As mentioned previously, the histogram analysis of SiO2-HA fiber composite to further confirm the average diameter of fiber composite and its distribution. The histogram analysis of SiO2-HA fiber composite was not provided.

Q3: You stated that "vibrational modes assigned to "...725 cm-1 for P2O74-"relate to the HA fibers spectrum. However, this vibration mode "P2O74-" is related to FTIR spectra of commercial product (Fluka β-TCP) according to the Ref [23].

Q4: As mentioned previously, I recommended the author to present the value of "crystallinity percentage", and "crystallite size" of HA and SiO2-HA in the table instead of Fig. 5. However, the crystallite size of HA and SiO2-HA was not presented.

Q5: "PO43- ions by HPO42-, Ca2+ by K+ or Mg2+, and OH- by F-, Cl-, Br-". Upper-case and lower-case should be used to indicate ions.

Q6: For readers' benefit, the schematic illustration regarding schematic demonstration of the interactions between the fibroblasts cell and surface of SiO2-HA could be presented.

Please submit your revised manuscript by Dec 11 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Hamid Reza Bakhsheshi-Rad

Academic Editor

PLOS ONE

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

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Cell behavior on Silica-Hydroxyapatite coaxial composite

PONE-D-20-16200R3

Dear Dr. Reyes-López,

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,

Hamid Reza Bakhsheshi-Rad

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: