A Self-Reinforcing Hydrogel Disrupting Osteoclast Sealing Zone for Bone Erosion Alleviation

A Self-Reinforcing Hydrogel Disrupting Osteoclast Sealing Zone for Bone Erosion Alleviation | 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 A Self-Reinforcing Hydrogel Disrupting Osteoclast Sealing Zone for Bone Erosion Alleviation Nan Li, Yilin Wei, Bei Kang, Baohong Liu, Wen Li, Yutong Song, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7827141/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 Abnormal remodeling of subchondral bone (SB), driven by osteoclast sealing zone formation and insufficient adaptation to joint mechanical stress, accelerates the progression of osteoarthritis (OA) and remains a major therapeutic challenge. In this study, we developed a mechanically self-reinforcing injectable hydrogel in which amino-hydroxyapatite (amHap)-encapsulating spindle-shaped tellurium (Te) nanoparticles were embedded within an oxidized alginate–gelatin matrix (Team Gel). Team Gel contains dynamic Schiff base bonds that enable controlled release of Team under joint mechanical forces. Within the acidic microenvironment of the osteoclast sealing zone, Team degrades and releases Te to be oxidized into TeO₃²⁻ by osteoclast-derived hydrogen peroxide. These ions can react with cysteine residues of F-actin to form Te–S bonds, which can lead to F-actin degradation to directly disrupt the sealing zone and suppress bone resorption. Notably, Ca²⁺ from amHap interacts with alginate to form an “eggshell” secondary crosslinking structure, which significantly increased the crosslinking density beyond the original Schiff base network, thereby enhancing the mechanical strength of Team Gel and extending its retention time. Acting in concert, PO₄³⁻-mediated inhibition of osteoclast differentiation and Te-driven disruption of mature osteoclast sealing zone synergistically suppress osteoclastogenesis and bone resorption. Such a “sealing zone disruption” strategy provides an effective means to preserve bone quality and maintain joint integrity, offering a promising paradigm for osteoclast-targeted therapy in OA. Biological sciences/Drug discovery/Pharmaceutics Biological sciences/Drug discovery/Drug delivery Self-reinforcing hydrogel Bone erosion Osteoclasts Sealing zone F-actin degradation Tellurium Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation.pdf Supplementary Information 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. 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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-7827141","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":529695640,"identity":"c22f1b7e-6e6d-4435-a097-0a1ede94c4d5","order_by":0,"name":"Nan 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In this study, we developed a mechanically self-reinforcing injectable hydrogel in which amino-hydroxyapatite (amHap)-encapsulating spindle-shaped tellurium (Te) nanoparticles were embedded within an oxidized alginate–gelatin matrix (Team Gel). Team Gel contains dynamic Schiff base bonds that enable controlled release of Team under joint mechanical forces. Within the acidic microenvironment of the osteoclast sealing zone, Team degrades and releases Te to be oxidized into TeO₃²⁻ by osteoclast-derived hydrogen peroxide. These ions can react with cysteine residues of F-actin to form Te–S bonds, which can lead to F-actin degradation to directly disrupt the sealing zone and suppress bone resorption. Notably, Ca²⁺ from amHap interacts with alginate to form an “eggshell” secondary crosslinking structure, which significantly increased the crosslinking density beyond the original Schiff base network, thereby enhancing the mechanical strength of Team Gel and extending its retention time. 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