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This study develops a fully humanized, animal\u2010free synovial membrane model, mimicking OA synovial structure and molecular profile. Protocols for rheumatoid synovial micromasses are adapted for 3D biochip cultures of OA synoviocytes using TISSEEL fibrin and ELAREM lysate. Cell activity, mRNA expression, and structural changes are evaluated under varying hydrogel stiffness and cytokine exposure, with results compared to human OA and animal (equine and murine) synovial tissues. The animal\u2010free biochip protocols replicate synovial architecture successfully. Improved gene expression of reticular collagen III (COL3A1) is achieved with 50\u00a0mg\u00a0mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    fibrinogen and 1% hPL. A 50 pg\u00a0mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    TNF\u2010\u03b1 and IL\u20101\u03b2 stimulus induced a pro\u2010fibrotic phenotype (COL1A1, COL3A1) distinct from the inflammatory response triggered by ng\/mL dosages (IL6, MMP1, MMP3, and MMP13, vs the pg\/mL model). The clinical relevance of the patient\u2010relevant OA synovial model is underscored by significant Yap1 overexpression, reflecting synovial hyperplasia from cell activation and inflammation. Yap1 distribution, as a biomarker (ctrl vs kOA tissue), is best replicated in the low\u2010dose pg\/ml\u2010treated model. The tissue\u2010mimetic biochips provide a human\u2010relevant OA study platform offering patient\u2010relevant molecular insights into the structure\u2010function relationships of osteoarthritic synovial tissues while eliminating animal\u2010derived materials.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202404799","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T02:54:39Z","timestamp":1751252079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An Animal\u2010Free Patient\u2010Derived Tissue\u2010Mimetic Biochip Model of the Human Synovial Membrane for Human\u2010Relevant Osteoarthritis Research"],"prefix":"10.1002","volume":"14","author":[{"given":"Eva I.","family":"Reihs","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Trauma Surgery, Karl Chiari Lab for Orthopaedic Biology Medical University of Vienna  Waehringer Guertel 18\u201320 Vienna 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