Nanozyme-Engineered Liners for Proactive Prevention of Wear Particle-induced Osteolysis

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Abstract Wear particle-induced osteolysis (WPO), primarily caused by particles generated from implants under mechanical loading, remains a major barrier to the long-term success of prosthetic implants. Traditional strategies to address WPO have largely focused on reducing wear generation, rather than mitigating the immunostimulatory effects elicited by wear particles. However, the mechanical improvement has its limitations, and the inevitable generation of wear particles urged us pay more attention to the biological improvement. Herein, we propose a “proactive preventive” strategy for liner design, aiming to effectively prevent WPO by simultaneously reducing the generation of wear particles and minimizing their immunostimulatory effects. To validate the feasibility of this strategy, we synthesized a model system by incorporating ceria nanozyme into ultra-high molecular weight polyethylene (UHMWPE), referred to as CZPE. Mechanical assessments demonstrate an about 32% reduction in wear particle production of CZPE compared with pristine UHMWPE. Moreover, CZPE particles elicited a markedly attenuated immune response compared to PE particles in a murine model of WPO, including reduced macrophage-mediated inflammation and diminished intramedullary plasma cell infiltration. These contributed to a reduction in osteoclastic bone resorption and foreign body reactions. Leveraging these mechanical and biological advantages, our approach offers a promising implant design strategy for WPO prevention.
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Nanozyme-Engineered Liners for Proactive Prevention of Wear Particle-induced Osteolysis | 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 Nanozyme-Engineered Liners for Proactive Prevention of Wear Particle-induced Osteolysis Hui Wei, Shujie Liu, Sheng Zhao, Qi Sun, Quanyi Liu, Yihong Zhang, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4022424/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Wear particle-induced osteolysis (WPO), primarily caused by particles generated from implants under mechanical loading, remains a major barrier to the long-term success of prosthetic implants. Traditional strategies to address WPO have largely focused on reducing wear generation, rather than mitigating the immunostimulatory effects elicited by wear particles. However, the mechanical improvement has its limitations, and the inevitable generation of wear particles urged us pay more attention to the biological improvement. Herein, we propose a “proactive preventive” strategy for liner design, aiming to effectively prevent WPO by simultaneously reducing the generation of wear particles and minimizing their immunostimulatory effects. To validate the feasibility of this strategy, we synthesized a model system by incorporating ceria nanozyme into ultra-high molecular weight polyethylene (UHMWPE), referred to as CZPE. Mechanical assessments demonstrate an about 32% reduction in wear particle production of CZPE compared with pristine UHMWPE. Moreover, CZPE particles elicited a markedly attenuated immune response compared to PE particles in a murine model of WPO, including reduced macrophage-mediated inflammation and diminished intramedullary plasma cell infiltration. These contributed to a reduction in osteoclastic bone resorption and foreign body reactions. Leveraging these mechanical and biological advantages, our approach offers a promising implant design strategy for WPO prevention. Physical sciences/Chemistry Physical sciences/Nanoscience and technology Full Text Additional Declarations Yes there is potential Competing Interest. Patent application is in progress. Supplementary Files SIrevisedwithallchanges.pdf SI_revised_with all changes SIrevisedwithhighlightsfinal.pdf SI_revised_with highlights_final 504073supp10599990spc18p.pdf Reporting Summary Cite Share Download PDF Status: Under Review 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. 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