biostudies-literatureVo QNHLBI NIH HHS2304630https://www.ebi.ac.uk/biostudies/studies/S-EPMC10923530biostudies-literatureUnknown34(10)Preclinical human-relevant modeling of organ-specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue-tissue, and cell-matrix interactions for a broad range of applications. Here, we present a reliable, and simply reproducible process for constructing user-controlled long rounded extracellular matrix (ECM)-embedded vascular microlumens on-chip for endothelization and co-culture with stromal cells obtained from human lung. We demonstrate the critical impact of microchannel cross-sectional geometry and length on uniform distribution and magnitude of vascular wall shear stress, which is key when emulating <i>in vivo</i>-observed blood flow biomechanics in health and disease. In addition, we provide an optimization protocol for multicellular cultureAdvanced functional materialsOn-Chip Reconstitution of Uniformly Shear-Sensing 3D Matrix-embedded Multicellular Blood Microvessel.PMC10923530R01 HL159494Vo QAjiboye ASCarlson KABenam KHWier EMChiknas PMBrocker CNDaSilva LPark SKClark EfalseOn-Chip Reconstitution of Uniformly Shear-Sensing 3D Matrix-embedded Multicellular Blood Microvessel.Preclinical human-relevant modeling of organ-specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue-tissue, and cell-matrix interactions for a broad range of applications. Here, we present a reliable, and simply reproducible process for constructing user-controlled long rounded extracellular matrix (ECM)-embedded vascular microlumens on-chip for endothelization and co-culture with stromal cells obtained from human lung. We demonstrate the critical impact of microchannel cross-sectional geometry and length on uniform distribution and magnitude of vascular wall shear stress, which is key when emulating <i>in vivo</i>-observed blood flow biomechanics in health and disease. In addition, we provide an optimization protocol for multicellular culture2024-01-01T00:00:00Z2024 Mar2025-04-18T12:54:58.058Z2025-04-06T22:17:02.039ZS-EPMC109235303846519910.1002/adfm.202304630