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However, investigation of the intricate FLS\u2010MLS interactions is limited by the lack of physiologically relevant in vitro models. Here, this work presents a synovium\u2010on\u2010a\u2010chip model that faithfully mimics the structural and functional properties of the human synovial lining, established with collagen\/alginate hybrid hydrogel (CAHG). The functional phenotype of FLS observed in vivo is replicated on chip when cultured with CAHG. Moreover, co\u2010culture with M2c macrophages derived from CD14+ monocytes enables the reconstruction of key immune functions of the synovial lining, including expression of junction proteins (ZO\u20101 and CLD5) and immunoregulatory markers (TREM2 and VSIG4). CD44 blockade, disrupting FLS\u2010MLS interactions, significantly suppresses inflammasome\u2010related pathways, underscoring the regulatory role of FLS in synovial immune responses. Our model is further validated by modeling gout, where treatment with monosodium urate crystals trigger NLRP3 inflammasome activation, macrophage polarization, and neutrophil extravasation. Pharmacological interventions with MCC950 and entrectinib effectively inhibit the inflammasome activation, demonstrating the platform's utility for preclinical drug evaluation. This synovium\u2010on\u2010a\u2010chip provides a reliable in vitro model for studying synovial inflammation and serves as a valuable tool for the therapeutic discovery of inflammatory joint diseases.<\/jats:p>","DOI":"10.1002\/adhm.202501471","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T15:31:29Z","timestamp":1748100689000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synovium\u2010on\u2010a\u2010Chip Reveals Fibroblast\u2013Macrophage Crosstalk Underpinning Joint Homeostasis and Evaluation of Gout Therapies"],"prefix":"10.1002","volume":"14","author":[{"given":"Min Seok","family":"Lee","sequence":"first","affiliation":[{"name":"Center for Infectious Disease Vaccine and Diagnosis Innovation (CEVI) Korea Research Institute of Chemical Technology (KRICT)  Daejeon 34114 Republic of 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00569-9"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/20420188241227295"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47640-7"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metop.2021.100100"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2731"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00466-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00736-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1088\/1758-5090\/ac0c5e"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/acf976"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874312901105010100"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2222-z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-021-02621-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202406668"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-020-02207-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12986"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj1252"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0939-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.715894"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1471-1"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220595"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.955806"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28663-4"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00744-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202301673"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/anbr.202000066"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-017-0060-3"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.9b07912"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.1c00129"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2612-2"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2022.01.008"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137306"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107392"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1263-7"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1352946"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-024-05777-4"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/gucdd1030012"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13322"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50806-9"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01084"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8111965"},{"key":"e_1_2_9_39_2","doi-asserted-by":"crossref","DOI":"10.1177\/03000605211055618","volume":"49","author":"Zhang 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