Synergistic Angio-Osteogenic Effects of Copper-Releasing 3D Biocomposite Scaffolds: A Step Toward Vascularized Bone Regeneration

Synergistic Angio-Osteogenic Effects of Copper-Releasing 3D Biocomposite Scaffolds: A Step Toward Vascularized 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 Article Synergistic Angio-Osteogenic Effects of Copper-Releasing 3D Biocomposite Scaffolds: A Step Toward Vascularized Bone Regeneration Saman Baghaei, Negar Azarpira, Maryam Paknahad, Ali Mohammad Amani, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7159849/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Critical-sized bone defects present significant clinical challenges due to inadequate vascularization and scaffold integration. This study developed a multifunctional 3D-printed polycaprolactone (PCL)-gelatin (Gel) scaffold reinforced with Bioglass particles (BGPs) or copper dopped BGPs (CuBGPs) to synergistically enhance angiogenesis and bone regeneration in rat model. The scaffolds were fabricated by infiltrating gelatin solutions containing BGPs or CuBGPs into the pores of 3D-printed PCL matrices, followed by freeze-drying. Comprehensive characterization of PCL-gel, PCL-gel-BGPs, and PCL-gel-CuBGPs scaffolds revealed optimal porosity (58.76±5.20, 53.27±11.83, and 54.5±7.61%), contact angle (74.53 ±6.6, 71.76±2.65, and 69.89±4.14), and controlled degradation (44.65±4.73, 47.93±2.51, and 50.58±5.68). MTT study demonstrated dose-dependent enhancement of cell proliferation, with BGPs and CuBGPs significantly improving mesenchymal stem cells (MSCs) viability by day 5. In vivo experiments in rat calvarial defects showed that Cu containing scaffolds promoted greater new bone volume compared to other groups at 12 weeks. Histological and immunohistochemical analyses confirmed robust angiogenesis and woven bone formation, with CuBGPs achieving the highest vasculature. This study provides a detailed and reproducible framework for Cu-doped scaffold fabrication, characterization, and application in critical-sized defect regeneration. Biological sciences/Biotechnology Physical sciences/Materials science Health sciences/Medical research Biological sciences/Stem cells Bone regeneration 3D-printing Bioglass Copper Angiogenesis Critical-sized defect Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7159849","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":504561512,"identity":"5605b60c-e025-45ae-92be-9c54c7229e7d","order_by":0,"name":"Saman Baghaei","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Saman","middleName":"","lastName":"Baghaei","suffix":""},{"id":504561513,"identity":"7ed9625f-dbd9-4aa6-b5ee-f9de2ba07c6c","order_by":1,"name":"Negar Azarpira","email":"","orcid":"","institution":"Shiraz University of Medical 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This study developed a multifunctional 3D-printed polycaprolactone (PCL)-gelatin (Gel) scaffold reinforced with Bioglass particles (BGPs) or copper dopped BGPs (CuBGPs) to synergistically enhance angiogenesis and bone regeneration in rat model. The scaffolds were fabricated by infiltrating gelatin solutions containing BGPs or CuBGPs into the pores of 3D-printed PCL matrices, followed by freeze-drying. Comprehensive characterization of PCL-gel, PCL-gel-BGPs, and PCL-gel-CuBGPs scaffolds revealed optimal porosity (58.76±5.20, 53.27±11.83, and 54.5±7.61%), contact angle (74.53 ±6.6, 71.76±2.65, and 69.89±4.14), and controlled degradation (44.65±4.73, 47.93±2.51, and 50.58±5.68). MTT study demonstrated dose-dependent enhancement of cell proliferation, with BGPs and CuBGPs significantly improving mesenchymal stem cells (MSCs) viability by day 5. 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