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In the degenerated intervertebral disc, there is an increase in the accumulation of reactive oxygen species (ROS) and the infiltration of M1 macrophages, which leads to abnormal local inflammatory microenvironment and exacerbates IDD. In this study, we developed a novel injectable polyethylene glycol (PEG)-capped cerium ion\u2013manganese ion (Ce\u2013Mn) bimetallic nanozyme (CeMn-PEG) with strong ROS scavenging and M2-type macrophage polarizing abilities to efficiently alleviate IDD. In\u00a0vitro experiments demonstrated that CeMn-PEG effectively scavenged excess ROS in both nucleus pulposus (NP) and RAW264.7 cells. In addition, we found that CeMn-PEG markedly protected NP cells from H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            -induced overproduction of inflammatory cytokines, excessive cell apoptosis and autophagy, and imbalance between extracellular matrix (ECM) degradation. Moreover, CeMn-PEG induced macrophages to transition from the M1 phenotype to the M2 phenotype and the increased M2-type macrophages could alleviate H\n            <jats:sub>2<\/jats:sub>\n            O\n            <jats:sub>2<\/jats:sub>\n            -induced ECM degradation and cell apoptosis in NP cells. In a puncture-induced mouse IDD model, CeMn-PEG treatment could effectively ameliorate the progression of disc degeneration and mitigate puncture-induced mechanical hyperalgesia. Thus, our study demonstrated the effectiveness of CeMn-PEG as a novel treatment strategy for the treatment of IDD and a range of other inflammatory diseases.\n          <\/jats:p>","DOI":"10.34133\/bmr.0118","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T20:19:57Z","timestamp":1733861997000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":25,"title":["Custom-Made Ce\u2013Mn Bimetallic Nanozyme for the Treatment of Intervertebral Disc Degeneration by Inhibiting Oxidative Stress and Modulating Macrophage M1\/M2 Polarization"],"prefix":"10.34133","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9730-1648","authenticated-orcid":false,"given":"Jianwei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zian","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haocheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosheng","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, \rGuangzhou University of Chinese Medicine, Guangzhou 510450, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital, \rFudan University, Shanghai 200000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"issue":"2","key":"e_1_3_5_2_2","first-page":"21","article-title":"Lumbar disc disorders and low-back pain: Socioeconomic factors and consequences","volume":"88","author":"Katz JN","year":"2006","unstructured":"Katz JN. 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