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In recent years, attention has shifted toward eradicating the source of synovial autoimmunity and inflammation, with a key focus on the synovial-draining lymphatics. However, very few\n                    <jats:italic>in vitro<\/jats:italic>\n                    models of the synovial microenvironment have been developed to date, and none yet include the synovial lymphatics. We therefore create a microfluidic chip device that models the synovial-draining lymphatics within the subintimal synovium microenvironment. Functional assays on our synovium-on-chip demonstrate increased lymphatic permeability and decreased drainage under RA inflammation compared to healthy controls, accompanied by increased lymphatic endothelial cell (LEC) junctional disruption and altered LEC phenotype following interaction with fibroblast-like synoviocytes. We identify overexpression of chitinase-3 like-protein-1 from RA patient-derived synoviocytes as a key target in inducing junctional loosening and lymphatic dysfunction, which is reversed in our microfluidic chip and in vivo mouse models by neutralizing antibody inhibition. Our novel synovium-on-chip model can provide a physiologically accurate representation of lymphatic drainage and activity under disease conditions, informing tissue engineering, drug testing, and high-throughput screening for RA.\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/ae9348","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:52:18Z","timestamp":1785538338000},"page":"035044","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Modeling the synovium on a chip for studying the interactions between lymphatic vasculature and synoviocytes in rheumatoid arthritis"],"prefix":"10.1088","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-1656","authenticated-orcid":true,"given":"Samantha E","family":"Kraus","sequence":"first","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9994-149X","authenticated-orcid":true,"given":"Issahy","family":"Cano","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5328-6677","authenticated-orcid":true,"given":"Esak","family":"Lee","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"bfae9348bib1","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nature01661","type":"journal-article","article-title":"Evolving concepts of rheumatoid arthritis","volume":"423","author":"Firestein","year":"2003","journal-title":"Nature"},{"key":"bfae9348bib2","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1002\/1529-0131(199811)41:11<1979::AID-ART13>3.0.CO;2-C","type":"journal-article","article-title":"Monoclonal expansion of synoviocytes in rheumatoid arthritis","volume":"41","author":"Imamura","year":"1998","journal-title":"Arthritis Rheum."},{"key":"bfae9348bib3","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1073\/pnas.91.7.2762","type":"journal-article","article-title":"Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis","volume":"91","author":"Williams","year":"1994","journal-title":"Proc. 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