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Ozone (O\n                    <jats:sub>3<\/jats:sub>\n                    ) shows potential therapeutic effects owing to its anti\u2010inflammatory properties; however, its high reactivity and short half\u2010life substantially limit its effectiveness in OA treatment. In this study, an ozone\u2010rich thermosensitive nanocomposite hydrogel loaded with D\u2010mannose is developed for OA treatment. Briefly, O\n                    <jats:sub>3<\/jats:sub>\n                    is encapsulated in nanoparticles (NPs) composed of perfluorotributylamine and fluorinated hyaluronic acid to improve its stability. Next, D\u2010mannose is conjugated with \u03b1\u2010amino of the hydroxypropyl chitin (HPCH) via Schiff base to prepare MHPCH. These nanoparticles are encapsulated in MHPCH to produce O\n                    <jats:sub>3<\/jats:sub>\n                    NPs@MHPCH. In vitro cell experiments demonstrate that the O\n                    <jats:sub>3<\/jats:sub>\n                    NPs@MHPCH treatment significantly reduced VEGF and inflammation levels, accompanied by a decrease in inflammatory factors such as IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, and iNOS. Furthermore, O\n                    <jats:sub>3<\/jats:sub>\n                    NPs@MHPCH promotes the expression of collagen II and aggrecan and stimulates chondrocyte proliferation. Additionally, in vivo studies show that O\n                    <jats:sub>3<\/jats:sub>\n                    NPs@MHPCH significantly alleviated OA by reducing synovial inflammation, cartilage destruction, and subchondral bone remodeling. O\n                    <jats:sub>3<\/jats:sub>\n                    NPs@MHPCH offers a promising option for improving the efficacy of O\n                    <jats:sub>3<\/jats:sub>\n                    therapy and reducing the risk of synovial inflammation and cartilage degeneration in OA.\n                  <\/jats:p>","DOI":"10.1002\/smll.202309597","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T02:30:11Z","timestamp":1706322611000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Injectable Ozone\u2010Rich Nanocomposite Hydrogel Loaded with D\u2010Mannose for Anti\u2010Inflammatory and Cartilage Protection in Osteoarthritis Treatment"],"prefix":"10.1002","volume":"20","author":[{"given":"Hangtian","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Orthopaedics and Traumatology Department of Orthopaedics Nanfang Hospital Southern Medical University  Guangzhou Guangdong 510515 P. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Cui","sequence":"additional","affiliation":[{"name":"Division of Orthopaedics and Traumatology Department of Orthopaedics Nanfang Hospital Southern Medical University  Guangzhou Guangdong 510515 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1414-0189","authenticated-orcid":false,"given":"Daogang","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Southern Medical University  Guangzhou 510515 P. R. China"},{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou 510515 P. R. 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