On‐Chip Reconstitution of Uniformly Shear‐Sensing 3D Matrix‐Embedded Multicellular Blood Microvessel

Abstract Preclinical human‐relevant modeling of organ‐specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue‐tissue, and cell‐matrix interactions for broad range applications. Here, this work presents reliable, simply reproducible process constructing user‐controlled long rounded extracellular matrix (ECM) embedded vascular microlumens on‐chip endothelization co‐culture with stromal cells obtained from human lung. This demonstrates the critical impact microchannel cross‐sectional geometry length on uniform distribution magnitude wall shear stress, which is key when emulating in vivo observed blood flow biomechanics health disease. In addition, study provides an optimization protocol multicellular culture functional validation system. Moreover, shows ability finely tune rheology three‐dimensional natural surrounding match stiffness. summary, scientific community matrix‐embedded microvasculature populated all‐primary human‐derived pulmonary endothelial fibroblasts recapitulate interrogate lung parenchymal biology, physiological responses, biomechanics, disease biogenesis vitro. Such mix‐and‐match synthetic platform can be feasibly adapted vessels, matrix, ECM‐embedded other organs cellularized additional cells.