<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="author-comment"><front><journal-meta><journal-id journal-id-type="nlm-ta">JMIRx Bio</journal-id><journal-id journal-id-type="publisher-id">xbio</journal-id><journal-id journal-id-type="index">35</journal-id><journal-title>JMIRx Bio</journal-title><abbrev-journal-title>JMIRx Bio</abbrev-journal-title><issn pub-type="epub">2819-2044</issn><publisher><publisher-name>JMIR Publications</publisher-name><publisher-loc>Toronto, Canada</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">v4i1e105278</article-id><article-id pub-id-type="doi">10.2196/105278</article-id><article-categories><subj-group subj-group-type="heading"><subject>Authors&#x2019; Response To Peer Reviews</subject></subj-group></article-categories><title-group><article-title>Authors&#x2019; Response to Peer Review of &#x201C;Material-Driven Therapeutics to Establish a Penetrating Traumatic Brain Injury Rat Model and Implantation of a 3D-Printed Scaffold: Pre-Experimental Pilot Study&#x201D;</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Harley-Troxell</surname><given-names>Meaghan E</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Dennis</surname><given-names>Michelle</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Dhar</surname><given-names>Madhu</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><institution>Tissue Engineering and Regenerative Medicine Lab, LACS, College of Veterinary Medicine, University of Tennessee at Knoxville</institution><addr-line>2407 River Drive</addr-line><addr-line>Knoxville</addr-line><addr-line>TN</addr-line><country>United States</country></aff><aff id="aff2"><institution>Biomedical and Diagnostic Sciences Department, College of Veterinary Medicine, University of Tennessee at Knoxville</institution><addr-line>Knoxville</addr-line><addr-line>TN</addr-line><country>United States</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Schwartz</surname><given-names>Amy</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Meaghan E Harley-Troxell, PhD, Tissue Engineering and Regenerative Medicine Lab, LACS, College of Veterinary Medicine, University of Tennessee at Knoxville, 2407 River Drive, Knoxville, TN, 37996, United States, 1 (865) 974-5703; <email>mharley-troxell@som.umaryland.edu</email></corresp></author-notes><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>10</day><month>7</month><year>2026</year></pub-date><volume>4</volume><elocation-id>e105278</elocation-id><history><date date-type="received"><day>22</day><month>06</month><year>2026</year></date><date date-type="accepted"><day>22</day><month>06</month><year>2026</year></date></history><copyright-statement>&#x00A9; Meaghan E Harley-Troxell, Michelle Dennis, Madhu Dhar. Originally published in JMIRx Bio (<ext-link ext-link-type="uri" xlink:href="https://bio.jmirx.org">https://bio.jmirx.org</ext-link>), 10.7.2026. </copyright-statement><copyright-year>2026</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIRx Bio, is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://bio.jmirx.org/">https://bio.jmirx.org/</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://bio.jmirx.org/2026/1/e105278"/><related-article related-article-type="preprint" ext-link-type="doi" xlink:href="10.1101/2025.03.20.644358" xlink:title="Preprint (medRxiv)" xlink:type="simple">https://www.biorxiv.org/content/10.1101/2025.03.20.644358v1</related-article><related-article related-article-type="reviewer-report" ext-link-type="doi" xlink:href="10.2196/105277" xlink:title="Peer-Review Report by Firas Kobeissy (Reviewer EW)" xlink:type="simple">https://bio.jmirx.org/2026/1/e105277</related-article><related-article related-article-type="reviewed-article" ext-link-type="doi" xlink:href="10.2196/75613" xlink:title="Published Article" xlink:type="simple">https://bio.jmirx.org/2026/1/e75613</related-article><kwd-group><kwd>penetrating traumatic brain injury</kwd><kwd>stereotaxic surgery</kwd><kwd>graphene</kwd><kwd>nerve tissue engineering</kwd><kwd>rat model</kwd></kwd-group></article-meta></front><body><p><italic>This is the authors&#x2019; response to the peer-review report for &#x201C;Material-Driven Therapeutics to Establish a Penetrating Traumatic Brain Injury Rat Model and Implantation of a 3D-Printed Scaffold: Pre-Experimental Pilot Study.&#x201D;</italic></p><sec id="s2"><title>Round 1 Review</title><sec id="s1-1"><title>Reviewer EW [<xref ref-type="bibr" rid="ref1">1</xref>]</title><list list-type="order"><list-item><p><italic>A key weakness of the study [<xref ref-type="bibr" rid="ref2">2</xref>] is its very small sample size (n=4), which substantially limits the statistical power, generalizability, and reliability of the conclusions. With such a low n, it becomes difficult to determine whether the observed variability&#x2014;particularly the severe inflammatory response in one animal&#x2014;reflects true biological differences, procedural inconsistencies, or random outliers.</italic></p><p><bold>Response:</bold> We agree that this study has a very small sample size. That does impose limitations on statistical power, results, and conclusions. We however have stressed throughout the manuscript that this is a &#x201C;pilot study&#x201D; to identify a technically feasible rat model. Since the aim of this study was to describe a model that could be used in future studies, only 4 animals were used, and results and conclusions based on those 4 animals are reported. After reporting this foundational study, we can now plan and initiate a study with control groups, a sufficient number of animals, and more detailed analyses. Some of these points are described in the Discussion section of the manuscript (lines 311&#x2010;316).</p></list-item><list-item><p><italic>The study lacks control groups&#x2014;including a sham surgery group and a traumatic brain injury&#x2013;only group&#x2014;preventing clear attribution of histological changes to either the injury model or the implanted scaffold.</italic></p><p><bold>Response:</bold> As described above in the response to comment 1, we agree that this study lacks control groups, including well-defined sham surgery or traumatic brain injury&#x2013;only groups. This will be taken into consideration in future studies, since we have established the feasibility of the technique in this manuscript. Some of these points are described in the Discussion section of the manuscript (lines 312&#x2010;316).</p></list-item><list-item><p><italic>The behavioral assessment is limited to a modified neurological severity score, which is often insensitive to mild or focal injuries and may miss subtle cognitive or sensorimotor deficits.</italic></p><p><bold>Response:</bold> Yes, we agree that the behavioral assessment reported in this study is limited. As described above in our responses to comments 1 and 2, this was a feasibility study. Since the number of animals was small, and there are a variety of behavioral assessments that are relevant and can be done, future studies will be planned accordingly. We will take into consideration the animal groups and their evaluations. Some of the results relevant to this feasibility study are described in the Results section of the manuscript (lines 223&#x2010;228).</p></list-item><list-item><p><italic>The study would be strengthened by incorporating additional validated behavioral tests.</italic></p><p><bold>Response:</bold> We agree, and after completing this feasibility study, we are ready and motivated to carry out a detailed study with additional groups and evaluations. Some of the results relevant to this study are described in the Results section of the manuscript (lines 225&#x2010;228).</p></list-item></list></sec></sec></body><back><ref-list><title>References</title><ref id="ref1"><label>1</label><nlm-citation citation-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Kobeissy</surname><given-names>F</given-names> </name></person-group><article-title>Peer review of "Material-Driven Therapeutics to Establish a Penetrating Traumatic Brain Injury Rat Model and Implantation of a 3D-Printed Scaffold: Pre-Experimental Pilot Study</article-title><source>JMIRx Bio</source><year>2026</year><volume>4</volume><fpage>e105277</fpage><pub-id pub-id-type="doi">10.2196/105277</pub-id></nlm-citation></ref><ref id="ref2"><label>2</label><nlm-citation citation-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Harley-Troxell</surname><given-names>ME</given-names> </name><name name-style="western"><surname>Dennis</surname><given-names>M</given-names> </name><name name-style="western"><surname>Dhar</surname><given-names>M</given-names> </name></person-group><article-title>Material-driven therapeutics to establish a penetrating traumatic brain injury rat model and implantation of a 3d-printed scaffold: pre-experimental pilot study</article-title><source>JMIRx Bio</source><year>2026</year><volume>4</volume><fpage>e75613</fpage><pub-id pub-id-type="doi">10.1101/2025.03.20.644358</pub-id></nlm-citation></ref></ref-list></back></article>