Micropillar-induced changes in cell nucleus morphology enhance bone regeneration by modulating the secretome

Micropillar-induced changes in cell nucleus morphology enhance bone regeneration by modulating the secretome | 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 Article Micropillar-induced changes in cell nucleus morphology enhance bone regeneration by modulating the secretome Guillermo Ameer, Xinlong Wang, Yiming Li, Zitong Lin, Indira Pla, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5530535/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Jul, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Nuclear morphology, which modulates chromatin architecture, plays a critical role in regulating gene expression and cell functions. While most research has focused on the direct effects of nuclear morphology on cell fate, its impact on the cell secretome and surrounding cells remains largely unexplored, yet is especially crucial for cell-based therapies. In this study, we fabricated implants with a micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites to investigate how micropillar-induced nuclear deformation influences cell paracrine signaling for osteogenesis and cranial bone regeneration. In vitro, cells with deformed nuclei showed enhanced secretion of proteins that support extracellular matrix (ECM) organization, which promoted osteogenic differentiation in neighboring human mesenchymal stromal cells (hMSCs). In a mouse model with critical-size cranial defects, nuclear-deformed hMSCs on micropillar mPOC/HA implants elevated Col1a2 expression, contributing to bone matrix formation, and drove cell differentiation toward osteogenic progenitor cells. These findings indicate that micropillars not only enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) but also modulate the secretome, thereby influencing the fate of surrounding cells through paracrine effects. Biological sciences/Biotechnology/Tissue engineering Biological sciences/Stem cells/Regeneration Health sciences/Medical research/Translational research Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable3.xlsx Supplementary Table 3 SupplementaryTable4.xlsx Supplementary Table 4 SupplementMicrotopographyinducedchangesincellnucleusmorphologyenhanceboneregenerationbymodulatingthecellularsecretome.pdf Microtopography-induced changes in cell nucleus morphology enhance bone regeneration by modulating the cellular secretome Cite Share Download PDF Status: Published Journal Publication published 11 Jul, 2025 Read the published version in Nature Communications → Version 1 posted 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. 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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-5530535","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":392258028,"identity":"4fdba979-0ac1-4442-83dd-8cd4a2a00adc","order_by":0,"name":"Guillermo 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