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Existing therapeutic agents often require frequent use, which can lead to drug resistance and long\u2010term side effects. Polyphenols have anti\u2010inflammatory and antioxidant potential. However, they are limited by their short half\u2010life and low bioavailability. This work presents a novel pure polyphenol capsule for sustained release of polyphenols, which is self\u2010assembled via hydrophobic and hydrogen bonds. The capsule enhances cellular uptake, scavenges reactive oxygen and nitrogen species, reduces inflammatory markers, and remodels the OA microenvironment by inhibiting the p38 MAPK pathway. The capsule overcomes the limitations of short half\u2010life and low bioavailability of polyphenols and achieves single\u2010dose cure in mouse and dog OA models, providing an optimal therapeutic window for OA repair. Taking advantage of simple manufacturing, convenient administration, and pure polyphenol composition, these capsules show great potential for clinical treatment of osteoarthritis and chronic inflammatory diseases.<\/jats:p>","DOI":"10.1002\/advs.202407425","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T14:29:16Z","timestamp":1731940156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ultra\u2010Long\u2010Term Anti\u2010Inflammatory Polyphenol Capsule to Remodel the Microenvironment for Accelerating Osteoarthritis Healing by Single Dosage"],"prefix":"10.1002","volume":"11","author":[{"given":"Shaoyin","family":"Wei","sequence":"first","affiliation":[{"name":"School of Ophthalmology and Optometry Eye Hospital School of Biomedical Engineering Wenzhou Medical University  Wenzhou 325035 China"},{"name":"Wenzhou Key Laboratory of Perioperative Medicine Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Shou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Zhuji Affiliated Hospital of Wenzhou Medical University  Shaoxing 311800 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry Eye Hospital School of Biomedical Engineering Wenzhou Medical University  Wenzhou 325035 China"},{"name":"Wenzhou Key Laboratory of Perioperative Medicine Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Diagnosis and Treatment of Severe Hepato\u2010Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical University  Wenzhou 325000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Advanced Materials for New Energy Storage and Conversion School of Materials Science and Engineering Hunan University of Science and Technology  Xiangtan 411201 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Wenzhou Key Laboratory of Perioperative Medicine Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-2913","authenticated-orcid":false,"given":"Xingjie","family":"Zan","sequence":"additional","affiliation":[{"name":"Wenzhou Key Laboratory of Perioperative Medicine Wenzhou Institute University of Chinese Academy of Sciences  Wenzhou 325001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong 250021 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunwu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Wenzhou Medical University  Wenzhou 325000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60802-3"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2018.08.003"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19702-z"},{"key":"e_1_2_10_2_3","first-page":"10","volume":"6","author":"Chen C. 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