Physicochemical and Biological Evaluation of Doxycycline-Loaded Polycaprolactone Nanofibers Produced by Solution Blow Spinning for Bone Regeneration

Physicochemical and Biological Evaluation of Doxycycline-Loaded Polycaprolactone Nanofibers Produced by Solution Blow Spinning for Bone Regeneration | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Physicochemical and Biological Evaluation of Doxycycline-Loaded Polycaprolactone Nanofibers Produced by Solution Blow Spinning for Bone Regeneration Lorena Gonçalves Henriques Corrêa Maduro, Bruna Nunes Teixeira, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8490440/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose To develop an ISO-guided in vitro evaluation solution of blow-spun polycaprolactone (PCL) nanofibrous mats loaded with doxycycline (DOX) as bioactive scaffolds for bone regeneration and localized antibiotic delivery. Methods PCL solutions (12% w/v, glacial acetic acid) were processed by solution blow spinning with 2, 4, and 8% (w/w, relative to PCL mass). Solution viscosity and surface tension were measured; SEM and image analysis assessed fiber morphology and diameter; FTIR verified chemical composition. Cytotoxicity of material extracts was tested in L-929 fibroblasts using the MTT assay according to ISO 10993-5:2009. Osteogenic bioactivity was assessed in SAOS-2 cultures by Alizarin Red staining and SEM–EDS analysis of calcium and phosphate deposition. Results DOX reduced solution viscosity without markedly altering surface tension and did not prevent fiber formation, although higher DOX concentrations increased bead occurrence. FTIR spectra were consistent with DOX incorporation, without apparent degradation. Extracts from 2% and 4% DOX mats met the ISO 10993-5 viability acceptance criterion, whereas 8% DOX fell below this threshold. All groups supported mineralized matrix formation, with qualitatively stronger calcium deposition on 4% DOX mats than on drug-free or 8% DOX mats. Conclusion Solution blow-spun PCL–DOX nanofibers, particularly at 4% DOX, provide an ISO-compliant in vitro evidence base for further development as bioactive scaffolds combining structural support and controlled antibiotic delivery. Follow-up work should quantify release kinetics and test performance in more biomimetic, advanced in vitro models. solution blow spinning nanofibers polycaprolactone doxycycline ISO 10993-5 mineralization Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Feb, 2026 Reviews received at journal 20 Feb, 2026 Reviewers agreed at journal 10 Jan, 2026 Reviews received at journal 05 Jan, 2026 Reviewers agreed at journal 05 Jan, 2026 Reviewers invited by journal 05 Jan, 2026 Editor assigned by journal 01 Jan, 2026 Submission checks completed at journal 01 Jan, 2026 First submitted to journal 31 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8490440","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":570094628,"identity":"308ff885-e224-44e1-8604-81aac72cb09a","order_by":0,"name":"Lorena Gonçalves Henriques Corrêa Maduro","email":"","orcid":"","institution":"Instituto Nacional de Metrologia, Qualidade e Tecnologia","correspondingAuthor":false,"prefix":"","firstName":"Lorena","middleName":"Gonçalves Henriques Corrêa","lastName":"Maduro","suffix":""},{"id":570094629,"identity":"4dcb7068-b680-430f-ac8c-a4ba59509aaf","order_by":1,"name":"Bruna Nunes 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Regeneration\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"in-vitro-models","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [In vitro models](https://link.springer.com/journal/44164)","snPcode":"44164","submissionUrl":"https://submission.springernature.com/new-submission/44164/3","title":"In vitro models","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"solution blow spinning, nanofibers, polycaprolactone, doxycycline, ISO 10993-5, mineralization","lastPublishedDoi":"10.21203/rs.3.rs-8490440/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8490440/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo develop an ISO-guided in vitro evaluation solution of blow-spun polycaprolactone (PCL) nanofibrous mats loaded with doxycycline (DOX) as bioactive scaffolds for bone regeneration and localized antibiotic delivery.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePCL solutions (12% w/v, glacial acetic acid) were processed by solution blow spinning with 2, 4, and 8% (w/w, relative to PCL mass). Solution viscosity and surface tension were measured; SEM and image analysis assessed fiber morphology and diameter; FTIR verified chemical composition. Cytotoxicity of material extracts was tested in L-929 fibroblasts using the MTT assay according to ISO 10993-5:2009. Osteogenic bioactivity was assessed in SAOS-2 cultures by Alizarin Red staining and SEM\u0026ndash;EDS analysis of calcium and phosphate deposition.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDOX reduced solution viscosity without markedly altering surface tension and did not prevent fiber formation, although higher DOX concentrations increased bead occurrence. FTIR spectra were consistent with DOX incorporation, without apparent degradation. Extracts from 2% and 4% DOX mats met the ISO 10993-5 viability acceptance criterion, whereas 8% DOX fell below this threshold. All groups supported mineralized matrix formation, with qualitatively stronger calcium deposition on 4% DOX mats than on drug-free or 8% DOX mats.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSolution blow-spun PCL\u0026ndash;DOX nanofibers, particularly at 4% DOX, provide an ISO-compliant in vitro evidence base for further development as bioactive scaffolds combining structural support and controlled antibiotic delivery. Follow-up work should quantify release kinetics and test performance in more biomimetic, advanced in vitro models.\u003c/p\u003e","manuscriptTitle":"Physicochemical and Biological Evaluation of Doxycycline-Loaded Polycaprolactone Nanofibers Produced by Solution Blow Spinning for Bone Regeneration","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-07 07:27:20","doi":"10.21203/rs.3.rs-8490440/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-21T12:04:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-21T03:28:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"334856673443699870519038024744133086","date":"2026-01-10T22:56:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-06T01:57:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62623419219370046822916984789133365697","date":"2026-01-06T00:34:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-05T17:29:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-02T04:35:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-02T02:15:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"In vitro models","date":"2025-12-31T14:09:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"in-vitro-models","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [In vitro models](https://link.springer.com/journal/44164)","snPcode":"44164","submissionUrl":"https://submission.springernature.com/new-submission/44164/3","title":"In vitro models","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"03bf223a-8bf1-4d39-aa00-96e4d944df58","owner":[],"postedDate":"January 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-10T21:53:44+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-07 07:27:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8490440","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8490440","identity":"rs-8490440","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}