Preparation and in vivo effectiveness evaluation of heparin-loaded PLGA@PCL core-shell fiber small-diameter vascular grafts

Yonghao Xiao; Han Wang; Yuhao Jiao; Yuehao Xing; Lin Ye; Ai-ying Zhang; Xue Geng; Fanshan Qiu; Zengguo Feng; Hongbo Chen; Yongquan Gu

doi:10.1371/journal.pone.0337192

Peer Review History

Original SubmissionJuly 4, 2024
12 Aug 2024 Decision Letter - Pradeep Kumar, Editor Dear Dr. wang, 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. ============================== as per the comments below from Reviewer 1 and reviewer 2. ============================== Please submit your revised manuscript by Sep 22 2024 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). 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Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Pradeep Kumar, Ph.D. Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information regarding the experiments involving animals and ensure you have included details on (1) methods of sacrifice, (2) methods of anesthesia and/or analgesia, and (3) efforts to alleviate suffering. 3. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: Fabrication and performance evaluation of PLCL-hCOLIII small-diameter vascular grafts crosslinked with procyanidins Author links open overlay panel - https://doi.org/10.1016/j.ijbiomac.2023.126293 Remodeling of structurally reinforced (TPU+PCL/PCL)-Hep electrospun small-diameter bilayer vascular grafts interposed in rat abdominal aortas - https://doi.org/10.1039/D1BM01653A (Among others) In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. 4. Thank you for stating the following financial disclosure: [This work was supported by the National Key R&D Program of China (No.2022YFC2409802) and the National Key R&D Program of China (2017YFC1104101).]. Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."" If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. 5. Thank you for stating the following in the Acknowledgments Section of your manuscript: [This work was supported by the National Key R&D Program of China (No.2022YFC2409802) and the National Key R&D Program of China (2017YFC1104101).] We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: [This work was supported by the National Key R&D Program of China (No.2022YFC2409802) and the National Key R&D Program of China (2017YFC1104101).] Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 6. In the online submission form, you indicated that [Data can be obtained by emailing the corresponding author of this article.]. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 7. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. 8. We note that Figure(s) 1, 3a and 4 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a. You may seek permission from the original copyright holder of Figure(s) 1, 3a and 4 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an ""Other"" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b. If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: No Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: No 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: In this study, a small-diameter artificial blood vessel was fabricated using PLGA@PCL core-shell fiber, and by immobilizing heparin on the surface, a highly patent graft was successfully obtained. Interestingly, the authors evaluated the data from material evaluation to in vivo experiments. On the other hand, many reports have described artificial blood vessels fabricated by electrospinning for a long time. For this reason, it is necessary to clarify the unique characteristics that are claimed in this study. Our primary comments are summarized below. 1. The definition of Core-Shell fiber, which is the focus of this paper, and its structure should be explained clearly, including schemes. 2. There are no data evaluating the characteristics of Core-Shell fiber, so please add this. 3. In vivo experiments excluded the control experiment. If stable patency rates and tissue regeneration can be induced by blood vessels made of Core-shell fiber, this should be discussed in comparison with the results of other types of fibers, such as those with no core-shell fibers as a control. Reviewer #2: The manuscript describe electrospinning of PLGA-PCL mat and surface functionalization with heparin. The electrospinning of PLGA-PCL core-shell mat is well studied area, authors developed small diameter tube out of it for vascular graft application. The work mainly focus on in-vivo studies and some physicochemical characterization Though the manuscript is written properly some issues need to addressed before consideration for publication Manuscript dosent have page and line no In section 2.1 Materials - sentence "N-Hydroxy succinimide was purchased from Sigma (St. Louis, MO, USA) was purchased from was purchased from Innochem (Beijing, China)" looks incomplete. In the same section please provide Ethics approval no. In section 2.2 Fabrication please clearly claim which polymer is forming core and which is forming shell In section 2.3 authors used many short forms (EDC, DIPEA, HOBT, NHS, MES etc); it might be from their previous publication, please provide full form of the same in this manuscript In section 2.4 and 2.5 authors should include more characterization like DCS, XRD etc to improve understanding on thermal and crystalline behavior of the scaffolds In section 2.6 Why author used type I Collagenase for degradation of polymers? in the same section "wt is the mass before degradation after accelerated degradation for 7 days" looks incomplete Section 2.8 Please check "werre was..") Section 2.9.1 authors mentioned that they kept SDVG in 75% alcohol for 20 min. have they studied the effect of alcohol on HCS? please compare it using FTIR Figure 1 Please provide the cross section of core-shell fiber Figure 4 (C-D) it should be (C-F) Just before figure 6 authors mentioned (Figure 8); there is no figure 8 in the manuscript In discussion please provide full form of VSMC ****** 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: Atsushi Mahara Reviewer #2: Yes: Dr. Ravindra Badhe ******** [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. https://doi.org/10.1371/journal.pone.0337192.r001
Revision 1
10 Oct 2024 Author Response Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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. Response: We have modified this paper to meet PLOS ONE's style requirements. 2. To comply with PLOS ONE submissions requirements, in your Methods section, please provide additional information regarding the experiments involving animals and ensure you have included details on (1) methods of sacrifice, (2) methods of anesthesia and/or analgesia, and (3) efforts to alleviate suffering. Response: The revised version has included these contents. 3. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: Fabrication and performance evaluation of PLCL-hCOLIII small-diameter vascular grafts crosslinked with procyanidins Author links open overlay panel - https://doi.org/10.1016/j.ijbiomac.2023.126293 Remodeling of structurally reinforced (TPU+PCL/PCL)-Hep electrospun small-diameter bilayer vascular grafts interposed in rat abdominal aortas - https://doi.org/10.1039/D1BM01653A (Among others) In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Response: We have made modifications to reduce the overlap with our published papers. 4. Thank you for stating the following financial disclosure: [This work was supported by the National Key R&D Program of China (No.2022YFC2409802) and the National Key R&D Program of China (2017YFC1104101).]. Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."" If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. Response: We have made modifications in the manuscript and the cover letter. 5. Thank you for stating the following in the Acknowledgments Section of your manuscript: [This work was supported by the National Key R&D Program of China (No.2022YFC2409802) and the National Key R&D Program of China (2017YFC1104101).] We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: [This work was supported by the National Key R&D Program of China (No.2022YFC2409802) and the National Key R&D Program of China (2017YFC1104101).] Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: We have made modifications in the manuscript and the cover letter. 6. In the online submission form, you indicated that [Data can be obtained by emailing the corresponding author of this article.]. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. Response: All data could be acquired within the manuscript itself. 7. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. Response: All experimental procedures were performed under institutional guidelines for animal care and approved by the Animal Ethics Committee of Fuwai Hospital Chinese Academy of Medical Sciences (Beijing, China). 8. We note that Figure(s) 1, 3a and 4 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a. You may seek permission from the original copyright holder of Figure(s) 1, 3a and 4 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an ""Other"" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b. If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Response: We believe that in the previous version, except picture 1, picture 3 and picture 4 do not involve copyright issues. In the newly revised version, we have also changed picture 1, so currently all images do not involve copyright issues. Reviewer #1: 1. The definition of Core-Shell fiber, which is the focus of this paper, and its structure should be explained clearly, including schemes. Response: We have modified the part 2.2 in order to explain the core-shell structure clearly. 2. There are no data evaluating the characteristics of Core-Shell fiber, so please add this. Response: Thanks for your comment. In this paper, we also characterized the surface morphology and core-shell structure of core-shell fibers by SEM and TEM, and studied the mechanical properties and degradation properties of the vascular graft after surface heparinization. For the surface fixed heparin, toluidine blue method and APTT method were also used to determine the content and release of heparin in vitro. At the same time, the core-shell fiber surface is heparin-modified PCL, which has been investigated for cytocompatibility and toxicity in our previous work (Hui X, et al. J Biomater Appl. 2020; 34 (6) : 812-826; Xiao Y, et al. Biomater Adv. 2024). In summary, as a small-caliber blood vessel, the characterization of the above properties can basically conclude that the core-shell fiber vascular graft in this submission can be used for carotid artery vascular transplantation in New Zealand white rabbits. 3. In vivo experiments excluded the control experiment. If stable patency rates and tissue regeneration can be induced by blood vessels made of Core-shell fiber, this should be discussed in comparison with the results of other types of fibers, such as those with no core-shell fibers as a control. Response: Thank you for your professional comments. We did conduct a long-term experiment of core-shell structure fiber and pure PCL fiber vascular graft in a rat model of abdominal aortic vascular transplantation and reported the corresponding experimental results (Xiao Y, et al. Biomater Adv. 2024; 165-214018; Fang Z., et al., Biomater.Sci.10 (2022) 4257-4270), small diameter vascular grafts using core-shell structure fibers have shown higher vascular patency rates and better elastin remodeling in the same animal model. Therefore, on the basis of this experiment, the carotid artery of New Zealand white rabbits was transplanted. The results of the experiment were compared with those of the double-layer vascular grafts performed earlier by our research group (Jin X, et al. Macromol Biosci. 2019; 19(8):e1900114; Hui X, et al. J Biomater Appl. 2020; 34(6):812-826) and surface heparinized vascular grafts have shown better resistance to vascular aneurysm occurrence, elastin remodeling, and vascular patency. At the same time, due to animal ethical considerations, pure PCL fibrovascular was not set as a control. Reviewer #2: 1.Manuscript dosent have page and line no. Response: We have added page and line number in the revised version. 2. In section 2.1 Materials - sentence "N-Hydroxy succinimide was purchased from Sigma (St. Louis, MO, USA) was purchased from was purchased from Innochem (Beijing, China)" looks incomplete. Response: We have completed this sentence. 3. In the same section please provide Ethics approval no. Response: The Ethics approval no. have been provided in the part of “Surgical procedures”. 4. In section 2.2 Fabrication please clearly claim which polymer is forming core and which is forming shell Response: We have modified the part 2.2 in order to explain the core-shell structure clearly. 5. In section 2.3 authors used many short forms (EDC, DIPEA, HOBT, NHS, MES etc); it might be from their previous publication, please provide full form of the same in this manuscript Response: We have provided full form of these short forms in the revised version. 6.In section 2.4 and 2.5 authors should include more characterization like DCS, XRD etc to improve understanding on thermal and crystalline behavior of the scaffolds Response: Thanks for your comment. In this paper, we also characterized the surface morphology and core-shell structure of core-shell fibers by SEM and TEM, and studied the mechanical properties and degradation properties of the vascular graft after surface heparinization. For the surface fixed heparin, toluidine blue method and APTT method were also used to determine the content and release of heparin in vitro. At the same time, the core-shell fiber surface is heparin-modified PCL, which has been investigated for cytocompatibility and toxicity in our previous work (Hui X, et al. J Biomater Appl. 2020; 34 (6) : 812-826; Xiao Y, et al. Biomater Adv. 2024). In summary, as a small-caliber blood vessel, the characterization of the above properties can basically conclude that the core-shell fiber vascular graft in this submission can be used for carotid artery vascular transplantation in New Zealand white rabbits. 7. In section 2.6 Why author used type I Collagenase for degradation of polymers? Response: Thanks a lot for this suggestion. This experiment was initially designed to investigate whether vascular grafts could be affected by matrix metalloproteinases during regeneration in vivo, and accordingly the more common type I collagenase was chosen as the active component of enzymatic degradation in vitro. 8. in the same section "wt is the mass before degradation after accelerated degradation for 7 days" looks incomplete Response: We have revised this sentence. 9.Section 2.8 Please check "werre was..") Response: We have revised this sentence. 10. Section 2.9.1 authors mentioned that they kept SDVG in 75% alcohol for 20 min. have they studied the effect of alcohol on HCS? please compare it using FTIR Response: We are very sorry that due to the existing experimental conditions and the limitation of raw materials, we cannot re-prepare the material and carry out this test at present. But based on our previous experience, alcohol immersion has no effect on the material structure. 11. Figure 1 Please provide the cross section of core-shell fiber Response: We are very sorry that due to the existing experimental conditions and the limitation of raw materials, we cannot re-prepare the material and recapture the picture of the materials. 12. Figure 4 (C-D) it should be (C-F) Response: We have revised this sentence. 13. Just before figure 6 authors mentioned (Figure 8); there is no figure 8 in the manuscript Response: We have revised it in the paragraph. 14. In discussion please provide full form of VSMC Response: we have provided the full name of VSMCs in the paragraph. Vascular smooth muscle cells (VSMCs). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0337192.r002
21 Nov 2024 Decision Letter - Pradeep Kumar, Editor Dear Dr. wang, These two comments need special attention: Reviewer #1: In general, results from animal experiments without control experiments are unacceptable in a scientific paper. The results using the grafts made with pure PCL in rabbits should be compared. Previous data using other animal species cannot be used as controls. Reviewer #2: The previous publication information should be properly linked to the current manuscript to strengthen the claim of continuation of the study. Please submit your revised manuscript by Jan 04 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. Please submit your revised manuscript by Jan 04 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'. 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 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Pradeep Kumar, Ph.D. Academic Editor PLOS ONE Journal Requirements: 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 Reviewer #1: (No Response) Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #1: (No Response) Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: (No Response) Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: (No Response) Reviewer #2: No ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: (No Response) Reviewer #2: Yes ****** Reviewer #1: In general, results from animal experiments without control experiments are unacceptable in a scientific paper. The results using the grafts made with pure PCL in rabbits should be compared. Previous data using other animal species cannot be used as controls. Reviewer #2: The previous publication information should be properly linked to the current manuscript to strengthen the claim of continuation of the study ****** 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: Yes: Ravindra Badhe ******** [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 https://doi.org/10.1371/journal.pone.0337192.r003
Revision 2
5 Mar 2025 Author Response Reviewer #1: In general, results from animal experiments without control experiments are unacceptable in a scientific paper. The results using the grafts made with pure PCL in rabbits should be compared. Previous data using other animal species cannot be used as controls. Response�Thanks for your conductive suggestions. We reapplied 4 more rabbits to verify pure PCL grafts in rabbit carotid artery grafting model. And the results of patency and livability were shown in Figure S1. Moreover, the regeneration of new tissue was characterized by tissue staining and immunohistochemistry. Reviewer #2: The previous publication information should be properly linked to the current manuscript to strengthen the claim of continuation of the study. Response�Thanks for your conductive suggestions. We have linked our previous publication to this paper in the part of “Discussion.” Attachments Attachment Submitted filename: response letter to reviewers (new).docx https://doi.org/10.1371/journal.pone.0337192.r004
24 Mar 2025 Decision Letter - Pradeep Kumar, Editor Dear Dr. wang, Please submit your revised manuscript by May 08 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'. 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 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Pradeep Kumar, Ph.D. Academic Editor PLOS ONE Journal Requirements: 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. Additional Editor Comments: The authors responded that "We reapplied 4 more rabbits to verify pure PCL grafts in rabbit carotid artery grafting model. And the results of patency and livability were shown in Figure S1." The authors should provide information on revised ethical approval details as well as incorporate Figure S1 in the main manuscript and discuss the same with the test group. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes ****** Reviewer #2: My queries are answered thank you ******** [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 https://doi.org/10.1371/journal.pone.0337192.r005
Revision 3
2 Sep 2025 Author Response Reviewer #1: In general, results from animal experiments without control experiments are unacceptable in a scientific paper. The results using the grafts made with pure PCL in rabbits should be compared. Previous data using other animal species cannot be used as controls. Response�Thanks for your conductive suggestions. We reapplied 4 more rabbits to verify pure PCL grafts in rabbit carotid artery grafting model. And the results of patency and livability were shown in Figure S1. Moreover, the regeneration of new tissue was characterized by tissue staining and immunohistochemistry. Reviewer #2: The previous publication information should be properly linked to the current manuscript to strengthen the claim of continuation of the study. Response�Thanks for your conductive suggestions. We have linked our previous publication to this paper in the part of “Discussion.” Attachments Attachment Submitted filename: response_letter_to_reviewers_(new)_auresp_3.docx https://doi.org/10.1371/journal.pone.0337192.r006
12 Oct 2025 Decision Letter - Pradeep Kumar, Editor Dear Dr. wang, 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 Nov 26 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'. 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 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Pradeep Kumar, Ph.D. Academic Editor PLOS ONE Journal Requirements: 1.I f 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. 2. 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. Additional Editor Comments: The supplementary Figure S1 is not provided with the revised manuscript and the reapplication ethical clearance certificate should have been provided. [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. https://doi.org/10.1371/journal.pone.0337192.r007
Revision 4
30 Oct 2025 Author Response 1.I f 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. Response�Thanks for your conductive suggestions. This article cites the literature previously published by my research team, mainly References 3, 9, 20, and 21. Among them, the vascular preparation methods involved in references 20 and 21 have great reference value for this paper. In this study, similar methods to those in previous studies were applied in the material preparation process, so References 20 and 21 have not been modified. However, after evaluation, we believed that references 3 and 9 could be deleted. We removed them and replaced them with other references. 2. 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. Response�Thanks for your conductive suggestions. The citation format of reference 7 is incomplete. We have made corresponding modifications. Reference 10 was previously a quoted web address. However, a latest reference has now been published, so this new reference has replaced the previous one. 3.The supplementary Figure S1 is not provided with the revised manuscript and the reapplication ethical clearance certificate should have been provided. Response�We have supplemented Figure S1 in the article. Currently, it is numbered Figure 5 in the article. In addition, we have uploaded the new ethical license certificate. 4.Other modifications This work was supported by the National Key R&D Program of China (2022YFC2409802). We have added information on financial support in the article In the previous version, the affiliated institutions of some authors were filled in incorrectly. We have made corrections Attachments Attachment Submitted filename: response letter to reviewers.docx https://doi.org/10.1371/journal.pone.0337192.r008
5 Nov 2025 Decision Letter - Pradeep Kumar, Editor Preparation and in vivo effectiveness evaluation of heparin-loaded PLGA@PCL core-shell fiber small-diameter vascular grafts PONE-D-24-24489R4 Dear Dr. wang, 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, Pradeep Kumar, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0337192.r009
Formally Accepted
Acceptance Letter - Pradeep Kumar, Editor PONE-D-24-24489R4 PLOS One Dear Dr. wang, 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 Prof. Pradeep Kumar Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0337192.r010

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