Patient and guardian perspectives on tissue engineering in microtia reconstruction

Arya Sherafat; James Antongiovanni; Chizoba Mosieri; Asthon Rosenbloom; Lana Mamoun; Sierra Willens; Leo Alaniz; Rahim Esfandyarpour; Mary Ziegler; Miles J. Pfaff

doi:10.1371/journal.pone.0338194

Peer Review History

Original SubmissionAugust 20, 2025
21 Oct 2025 Decision Letter - Arash Ghalandarzadeh, Editor Dear Dr. Pfaff, 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. Please submit your revised manuscript by Dec 05 2025 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. 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'. 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We look forward to receiving your revised manuscript. Kind regards, Arash Ghalandarzadeh, Ph.D. Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information . 3. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 4. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [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? Reviewer #1: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: The study addresses an important and emerging area in reconstructive surgery—patient and guardian perspectives on tissue engineering for microtia—which has clear clinical and translational relevance. I commend the authors for undertaking this work, engaging directly with patients and families, and presenting novel data in a field where patient-centered perspectives are often underrepresented. My comments below aim to strengthen the manuscript by clarifying the methods, ensuring appropriate use of statistical analyses, and refining the presentation of results and conclusions. I have organized my feedback into major and minor points, with the goal of providing constructive suggestions to enhance the rigor, clarity, and impact of this valuable contribution. 1. Small Sample Size vs. Complex Multivariate Models: The study involves 40 surveys and the use of multivariate/ordinal logistic regressions. Given the likely low events-per-variable ratio, there is a risk of overfitting. Please report the number of predictors per model, consider using simpler models, or apply penalized/Firth logistic regression with accompanying model diagnostics (AIC, goodness-of-fit). If none of these options are feasible, I recommend removing overambitious multivariate claims. 2. Ambiguity Regarding Timing of Educational Material: The methods state that an educational document was “distributed… prior to the initiation of the survey,” yet the results indicate participants’ familiarity was assessed “before receiving supplemental educational material.” This is contradictory; please clarify whether baseline familiarity was assessed before participants viewed the material (preferred) or retrospectively after viewing. If the latter, discuss potential recall and information bias. 3. Insufficient Description of COI (Child Opportunity Index) Mapping and Categories: Please describe how zip codes were mapped to the COI and detail the cut-offs used for “low,” “high,” and “very high.” Additionally, present the distribution of participants across COI strata, and discuss the potential ecological fallacy of using area-level COI as a proxy for individual socioeconomic status (SES). 4. Abstract — Statistics: Avoid stating specific p-values for numerous small comparisons in the abstract; instead, summarize the key statistically significant findings. Aim to keep the abstract concise. 5. Definition of Abbreviations on First Use: For instance, "COI" is used before its full name is explained in the Methods section. Ensure that all abbreviations are defined upon their first use for clarity. 6. Consider Reporting Effect Sizes: For key comparisons, include effect sizes (Cohen’s d, rank-biserial correlation) to better interpret clinical relevance beyond p-values. 7. Add a Short “Implications for Practice / Next Steps” Paragraph: Given the findings, briefly outline practical recommendations for clinicians (e.g., provider education about tissue engineering, targeted outreach to low-COI communities). However, tie these recommendations to the study limitations to ensure they remain proportional. Reviewer #2: This manuscript is technically sounds and well-written. The reviewer only has few minor concerns. 1. Tissue engineering is a broad terminology. Upon presenting this TE idea to patients, how do authors be certain that their patients could have through understanding of TE in the application of ear reconstruction? 2. The authors should also consider if there is sex-difference factors in making the decision, especially the survey participants in this study are mostly female. 3. The table is very blur (the reviewer had hard time to go over each questions). It is suggested to make the visual presentation more appealing. 4. What are the other races in the survey participants? ****** 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: Yes: Milad hosseini 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.] To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. Attachments Attachment Submitted filename: comments.docx https://doi.org/10.1371/journal.pone.0338194.r001
Revision 1
18 Nov 2025 Author Response The responses to comments have been included in a separate document attached and included here for reference: 1. Small Sample Size vs. Complex Multivariate Models: The study involves 40 surveys and the use of multivariate/ordinal logistic regressions. Given the likely low events-per-variable ratio, there is a risk of overfitting. Please report the number of predictors per model, consider using simpler models, or apply penalized/Firth logistic regression with accompanying model diagnostics (AIC, goodness-of-fit). If none of these options are feasible, I recommend removing overambitious multivariate claims. a. We appreciate this feedback and agree with the reviewer on the risk of overfitting and have incorporated this feedback into the limitation portion of our study. Multiple analysis methods were included in this study with simple two-sample t-test as a mode of primary data results. Additional multivariate analysis were exploratory and aimed to provide insight through a greater context of the study. Multivariate claims, including patient demographic claims, were removed from this study to better reflect the primary data. Of note, this is single institution study with early data exploring patient perspectives. Disscussion on increasing sample size to validate the associations made in this study have been included in the future directions of this study. 2. Ambiguity Regarding Timing of Educational Material: The methods state that an educational document was “distributed… prior to the initiation of the survey,” yet the results indicate participants’ familiarity was assessed “before receiving supplemental educational material.” This is contradictory; please clarify whether baseline familiarity was assessed before participants viewed the material (preferred) or retrospectively after viewing. If the latter, discuss potential recall and information bias. a. Thank you for this comment and feedback on our educational material distribution methods. Our survey included the following two questions to assess familiarity prior to distribution of the educational material: (1) “Have you heard of Tissue Engineering before today?” and (2) “Did you know what Tissue Engineering is before today?” Survey distribution was initiated after the introduction educational material and these two questions were used as retrospective proxys to assess familiarity prior to that material. For further clarification for the reader, the introductory sentence of our “Quantitative Survey Evaluation” portion of the methods in the manuscript has been adapted to reflect this. Additionally, a comment regarding potential recall and information bias has been added to the limitations of this study to provide additional context. 3. Insufficient Description of COI (Child Opportunity Index) Mapping and Categories: Please describe how zip codes were mapped to the COI and detail the cut-offs used for “low,” “high,” and “very high.” Additionally, present the distribution of participants across COI strata, and discuss the potential ecological fallacy of using area-level COI as a proxy for individual socioeconomic status (SES). a. Thank you for this comment. Child Opportunity Index (COI) zip code mapping is done in accordance to the datasets available at diversitydatakids.org. As for the COI 3.0, which was used for our research, 44 content area indicators were incorporated into the score for COI including: i. “Early childhood education, elementary education, secondary and post-secondary education, education resources, pollution, healthy environments, safety- and health-related resources, economic opportunities, economic resources, concentrated inequity, housing resources, social resources, wealth” ii. Composite z scores of these indicators were calculated and grouped by the following: iii. “census tracts with composite z-scores at or below the 20th population-weighted 2023 percentile were sorted into the “very low” group. Tracts above the 20th and at or below the 40th population-weighted 2023 percentile were classified as “low opportunity.” Tracts above the 40th and at or below the 60th population-weighted 2023 percentile were classified as “moderate opportunity,” tracts above the 60th and at or below the 80th population-weighted 2023 percentile were classified as “high opportunity” and tracts above the 80th population-weighted 2023 percentile were classified as “very high opportunity.”” b. These methods are further expanded upon in the manuscript in the “Data Analysis & Grouping” Section c. The distribution of COI strata for our study is included in Table 1 which outlines the following: Very Low (5), Low (17), Moderate (5), High (3), Very High (10). d. The ecological fallacy of using area level COI as a proxy for SES was added to the limitations portion of this manuscript. 4. Abstract — Statistics: Avoid stating specific p-values for numerous small comparisons in the abstract; instead, summarize the key statistically significant findings. Aim to keep the abstract concise. a. The abstract has been adapted to exclude specific p values and contains only key statistical findings. The abstract has been made consice for clarity. 5. Definition of Abbreviations on First Use: For instance, "COI" is used before its full name is explained in the Methods section. Ensure that all abbreviations are defined upon their first use for clarity. a. Thank you for this consideration. The manuscript has been screened for abbreviation definitions on first use and should be up to date. “Childhood Opportunity Index” is first introduced and defined as “COI” in on first use and is abbreviated in all of the following lines of the manuscript. 6. Consider Reporting Effect Sizes: For key comparisons, include effect sizes (Cohen’s d, rank-biserial correlation) to better interpret clinical relevance beyond p-values. a. We appreciate the reviewers suggestion to include effect sizes however, given the exploratory nature of our study and smaller sample size, we chose not to include formal effect size estimates. We have, however, aimed to elaborate in the clinical relevance of our findings in the discussion. 7. Add a Short “Implications for Practice / Next Steps” Paragraph: Given the findings, briefly outline practical recommendations for clinicians (e.g., provider education about tissue engineering, targeted outreach to low-COI communities). However, tie these recommendations to the study limitations to ensure they remain proportional. a. We agree with the reviewer that additional recommendations for clinicians should be added to the discussion of this manuscript. This has been added to the discussion portion of our manuscript. Our “implications for practice / next steps” paragraph aims to discuss the importance of provider education and targeted outreach for TE-based reconstruction. Attachments Attachment Submitted filename: Reviewer Feedback - TE Perspectives.docx https://doi.org/10.1371/journal.pone.0338194.r002
20 Nov 2025 Decision Letter - Arash Ghalandarzadeh, Editor Patient and Guardian Perspectives on Tissue Engineering in Microtia Reconstruction PONE-D-25-44361R1 Dear Dr. J. Pfaff, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . 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, Arash Ghalandarzadeh, Ph.D. Student Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: The author has adequately addressed all comments, and the manuscript is suitable for publication. https://doi.org/10.1371/journal.pone.0338194.r003
Formally Accepted
Acceptance Letter - Arash Ghalandarzadeh, Editor PONE-D-25-44361R1 PLOS One Dear Dr. Pfaff, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@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 Mr. Arash Ghalandarzadeh Guest Editor PLOS One https://doi.org/10.1371/journal.pone.0338194.r004

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