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Conventional in vivo models struggle to isolate and study the specific effects of mechanical stress on cartilage health. To address this limitation, a microphysiological system (MPS) is established to examine how varying levels of shear stress impact cartilage homeostasis. The system allows for the cultivation of 3D chondrogenic microconstructs (CMCs) derived from human mesenchymal stromal cells, simulating both physiological and pathophysiological shear stress. Inflammation is induced via TNF\u2010\u03b1 or activated peripheral blood mononuclear cells to model cartilage damage, enabling the evaluation of therapeutic interventions. The study demonstrates the development of an arthritis\u2010like phenotype and successful restoration of cartilage conditions through a JAK inhibitor under physiological shear stress. Physiological shear stress is identified as a critical factor in maintaining cartilage integrity. This MPS offers a standardized method to study shear stress, replicate cytokine\u2010induced cartilage damage, and simulate key features of arthritis, providing a valuable alternative to animal models.<\/jats:p>","DOI":"10.1002\/advs.202412010","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T03:15:43Z","timestamp":1735010143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Microphysiological System\u2010Generated Physiological Shear Forces Reduce TNF\u2010\u03b1\u2010Mediated Cartilage Damage in a 3D Model of Arthritis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-2963","authenticated-orcid":false,"given":"Alexandra","family":"Damerau","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  10117 Berlin Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin a Leibniz Institute  10117 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duc Ha Do","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  10117 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Lubahn","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  10117 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6865-4084","authenticated-orcid":false,"given":"Kasper","family":"Renggli","sequence":"additional","affiliation":[{"name":"School of Life Sciences University of Applied Sciences and Arts Northwestern Switzerland  Muttenz 4132 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6327-2343","authenticated-orcid":false,"given":"Moritz","family":"Pfeiffenberger","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  10117 Berlin Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin a Leibniz Institute  10117 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-4325","authenticated-orcid":false,"given":"Gerhard","family":"Kr\u00f6nke","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  10117 Berlin Germany"},{"name":"German Rheumatism Research Centre (DRFZ) Berlin a Leibniz Institute  10117 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Immunology &amp; 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