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Current therapies primarily rely on general immune suppression, often leading to suboptimal outcomes and significant side effects. To address these challenges, an interleukin\u20104 (IL\u20104)\u2010tethered, hyaluronic acid\u2010based hydrogel is developed that withstands repeated mechanical stress in the joint space while fostering an immunomodulatory environment. The immunosuppressive hydrogel promotes anti\u2010inflammatory M2 macrophage polarization, creating an anti\u2010inflammatory microenvironment while preserving cartilage and mitigating joint damage. The mechanical properties of the hydrogel are carefully optimized for injectability and intra\u2010articular application. Its effectiveness is evaluated in a collagen\u2010induced arthritis (CIA) mouse model, demonstrating potential as a localized therapeutic approach. It is believed that this IL\u20104\u2010tethered hydrogel platform will provide a foundation for the combinatorial treatment of RA and various inflammatory diseases.<\/jats:p>","DOI":"10.1002\/adhm.202501613","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T07:19:09Z","timestamp":1748243949000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immunosuppressive Cytokine\u2010Tethered Hydrogel for Treating Rheumatoid Arthritis"],"prefix":"10.1002","volume":"14","author":[{"given":"Woojin","family":"Back","sequence":"first","affiliation":[{"name":"Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moonkyoung","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huyen\u2010Thao","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0721-0428","authenticated-orcid":false,"given":"Ji\u2010Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01525-8"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.022053"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3785"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh3693"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204816"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2103726"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.0c00295"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NA00229A"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7BM00254H"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2017.1372746"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/978351"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c04491"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.159"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.71"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4BM00035H"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10227"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adc8738"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar1916"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00712-1"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.4.2.5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202306554"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201003963"},{"key":"e_1_2_9_24_1","volume-title":"Hyaluronic Acid: Production, Properties, Application in biology and Medicine","author":"Khabarov V. 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