Mechanobiologically-optimized non-resorbable artificial bone – a new paradigm in patient-matched scaffold-guided bone regeneration

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Abstract

Abstract Patient-matched scaffold guided bone regeneration (SGBR) has been poised to revolutionize the management of critical-sized bone defects due to trauma, tumors, infection, and congenital deformities. However, translation has been hampered by the focus on bioresorbable scaffolds where the rate of scaffold degradation needs to be precisely and predictably matched to the rate of new bone formation. Furthermore, resorbable ceramics and polymers require augmentation by metal plates to overcome their mechanical limitations under load. Consequently, there are no published studies using SGBR for segmental defects without metal plates, which cause stress shielding and X-ray perturbation. Even with augmentation, very few studies use animal models where the loads are comparable to humans. Segmental defects of the mandible represent one of the most challenging examples of critical-sized bone defects due to the high tensile and shear stresses encountered during mastication. The ovine mandible is an excellent model because the high and repetitive loads exceed those encountered in humans. Here, we describe the first successful long-term reconstruction of ovine segmental mandibulectomy defects using permanent, patient-matched, numerically optimized, 3D-printed, thermally toughened, plasma-treated, and selectively-laser-sintered polyetherketone gyroid scaffolds. The scaffolds house a resorbable ceramic lattice infused with a stem cell laden hydrogel and serve as an osteoinductive reservoir of calcium. Durable clinical performance and osseointegration was established in vivo and ex vivo, indicating for the first time that there is a reliable and translatable patient-matched SGBR alternative to traditional bone grafts and metal plate fixation.
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Mechanobiologically-optimized non-resorbable artificial bone – a new paradigm in patient-matched scaffold-guided 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 Mechanobiologically-optimized non-resorbable artificial bone – a new paradigm in patient-matched scaffold-guided bone regeneration Jonathan Clark, Jeremy Crook, D S Abdullah Al Maruf, Eva Tomaskovic-Crook, and 22 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6118157/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Oct, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Patient-matched scaffold guided bone regeneration (SGBR) has been poised to revolutionize the management of critical-sized bone defects due to trauma, tumors, infection, and congenital deformities. However, translation has been hampered by the focus on bioresorbable scaffolds where the rate of scaffold degradation needs to be precisely and predictably matched to the rate of new bone formation. Furthermore, resorbable ceramics and polymers require augmentation by metal plates to overcome their mechanical limitations under load. Consequently, there are no published studies using SGBR for segmental defects without metal plates, which cause stress shielding and X-ray perturbation. Even with augmentation, very few studies use animal models where the loads are comparable to humans. Segmental defects of the mandible represent one of the most challenging examples of critical-sized bone defects due to the high tensile and shear stresses encountered during mastication. The ovine mandible is an excellent model because the high and repetitive loads exceed those encountered in humans. Here, we describe the first successful long-term reconstruction of ovine segmental mandibulectomy defects using permanent, patient-matched, numerically optimized, 3D-printed, thermally toughened, plasma-treated, and selectively-laser-sintered polyetherketone gyroid scaffolds. The scaffolds house a resorbable ceramic lattice infused with a stem cell laden hydrogel and serve as an osteoinductive reservoir of calcium. Durable clinical performance and osseointegration was established in vivo and ex vivo, indicating for the first time that there is a reliable and translatable patient-matched SGBR alternative to traditional bone grafts and metal plate fixation. Biological sciences/Biotechnology/Biomaterials/Implants Biological sciences/Biotechnology/Tissue engineering Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Clarketal2024SupplementaryFiguresXtableNaturecommunicationPDF.pdf Supplementary Figures and table ClarketalSupplementaryVideo1Naturecommunication.mp4 Sheep chewing behavior ClarketalSupplementaryVideo2Naturecommunication.mp4 Stress-driven CBCT bone growth patterns Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 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. We do this by developing innovative software and high quality services for the global research community. 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