{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:45:27Z","timestamp":1791974727360,"version":"4.4.0"},"reference-count":83,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Lymphatic vessels (LVs) maintain fluid homeostasis by draining interstitial fluid. A failure in lymphatic drainage triggers lymphatic diseases such as lymphedema. Since lymphatic drainage is regulated by lymphatic barrier function, developing experimental models that assess lymphatic barrier function is critical for better understanding of lymphatic physiology and disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We built a lymphatic vessel\u2010on\u2010chip (LV\u2010on\u2010chip) by fabricating a microfluidic device that includes a hollow microchannel embedded in three\u2010dimensional (3D) hydrogel. Employing luminal flow in the microchannel, human lymphatic endothelial cells (LECs) seeded in the microchannel formed an engineered LV exhibiting 3D conduit structure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lymphatic endothelial cells formed relatively permeable junctions in 3D collagen 1. However, adding fibronectin to the collagen 1 apparently tightened LEC junctions. We tested lymphatic barrier function by introducing dextran into LV lumens. While LECs in collagen 1\u00a0showed permeable barriers, LECs in fibronectin\/collagen 1\u00a0showed reduced permeability, which was reversed by integrin \u03b15 inhibition. Mechanistically, LECs expressed inactivated integrin \u03b15 in collagen 1. However, integrin \u03b15 is activated in fibronectin and enhances barrier function. Integrin \u03b15 activation itself also tightened LEC junctions in the absence of fibronectin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lymphatic vessel\u2010on\u2010chip reveals integrin \u03b15 as a regulator of lymphatic barrier function and provides a platform for studying lymphatic barrier function in various conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/micc.12730","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T15:02:57Z","timestamp":1632754977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["A bioengineered lymphatic vessel model for studying lymphatic endothelial cell\u2010cell junction and barrier function"],"prefix":"10.1111","volume":"28","author":[{"given":"Aria R.","family":"Henderson","sequence":"first","affiliation":[{"name":"Nancy E. and Peter C. Meinig School of Biomedical Engineering Cornell University Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle S.","family":"Ilan","sequence":"additional","affiliation":[{"name":"College of Human Ecology Cornell University Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esak","family":"Lee","sequence":"additional","affiliation":[{"name":"Nancy E. and Peter C. 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