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Here, this work presents a reliable, and simply reproducible process for constructing user\u2010controlled long rounded extracellular matrix (ECM) embedded vascular microlumens on\u2010chip for endothelization and co\u2010culture with stromal cells obtained from human lung. This work demonstrates the critical impact of microchannel cross\u2010sectional geometry and length on uniform distribution and magnitude of vascular wall shear stress, which is key when emulating in vivo observed blood flow biomechanics in health and disease. In addition, this study provides an optimization protocol for multicellular culture and functional validation of the system. Moreover, this study shows the ability to finely tune rheology of the three\u2010dimensional natural matrix surrounding the vascular microchannel to match pathophysiological stiffness. In summary, this work provides the scientific community with a matrix\u2010embedded microvasculature on\u2010chip populated with all\u2010primary human\u2010derived pulmonary endothelial cells and fibroblasts to recapitulate and interrogate lung parenchymal biology, physiological responses, vascular biomechanics, and disease biogenesis in vitro. Such a mix\u2010and\u2010match synthetic platform can be feasibly adapted to study blood vessels, matrix, and ECM\u2010embedded cells in other organs and be cellularized with additional stromal cells.<\/jats:p>","DOI":"10.1002\/adfm.202304630","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T06:00:02Z","timestamp":1691388002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["On\u2010Chip Reconstitution of Uniformly Shear\u2010Sensing 3D Matrix\u2010Embedded Multicellular Blood Microvessel"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2270-1532","authenticated-orcid":false,"given":"Quoc","family":"Vo","sequence":"first","affiliation":[{"name":"Division of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaely A.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh PA 15219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Chiknas","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh  Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad N.","family":"Brocker","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products U.S. Food and Drug Administration  Silver Spring MD 20993 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"DaSilva","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products U.S. Food and Drug Administration  Silver Spring MD 20993 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Clark","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products U.S. Food and Drug Administration  Silver Spring MD 20993 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products U.S. Food and Drug Administration  Silver Spring MD 20993 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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