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However, current models have limited success at accurately simulating in vivo microenvironment and lacking intricate cellular cross\u2010talk. Here, this work presents a human in vitro RA model that faithfully captures functional and compositional properties of cartilage and synovial lining in vivo, established with chondrocytes recellularized type II collagen scaffold and 3D\u2010bioprinted bi\u2010layered Gelatin\u2010Matrigel hydrogel incorporating fibroblast\u2010like synoviocytes (FLS) and proinflammatory macrophages in the top layer and protective barrier macrophages in the bottom layer. This synovium\u2010cartilage system recapitulates key inflammatory processes akin to RA, including enhanced production of proinflammatory mediators and degradative enzymes, as well as reactive oxygen species generation, invasion of FLS into cartilage, phenotypic alterations of macrophages and the depletion of cartilaginous extracellular matrix components. The established model enables effective screening of anti\u2010arthritis drugs, which is validated by leveraging celecoxib and tofacitinib. Furthermore, the transcriptomic and proteomic landscape of this model demonstrates accuracy in replicating in vivo pathological conditions. Notably, this in vitro model reflects the response of the disease to the drug compared to the rat model of RA. Overall, this study provides reliable in vitro human synovium\u2010cartilage models for screening preclinical drugs in RA therapeutics.<\/jats:p>","DOI":"10.1002\/adma.202513952","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:04:22Z","timestamp":1765602262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["3D Bioprinted Human Synovium\u2010Cartilage Models Mimic Rheumatoid Arthritis Microenvironment and Recapitulate In Vivo Therapeutic Responses"],"prefix":"10.1002","volume":"38","author":[{"given":"Huiqun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Chinese University of Hong Kong  Sha Tin, New Territories Hong Kong SAR 999077 China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine InnoHK HKSTP  Sha Tin, New Territories Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering City University of Hong Kong  83 Tat Chee Avenue, Kowloon Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulei","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering City University of Hong Kong  83 Tat Chee Avenue, Kowloon Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Chinese University of Hong Kong  Sha Tin, New Territories Hong Kong SAR 999077 China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine InnoHK HKSTP  Sha Tin, New Territories Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Neuromusculoskeletal Restorative Medicine InnoHK HKSTP  Sha Tin, New Territories Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Chinese University of Hong Kong  Sha Tin, New Territories Hong Kong SAR 999077 China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine InnoHK HKSTP  Sha Tin, New Territories Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-1422","authenticated-orcid":false,"given":"Dong\u2010An","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Chinese University of Hong Kong  Sha Tin, New Territories Hong Kong SAR 999077 China"},{"name":"Center for Neuromusculoskeletal Restorative Medicine InnoHK HKSTP  Sha Tin, New Territories Hong Kong SAR 999077 China"},{"name":"Karolinska Institutet Ming Wai Lau Centre for Reparative Medicine HKSTP  Sha Tin Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"5","author":"Black R. 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