Engineering perfusable vascular networks in organoids-on-chip [bulk RNA-seq]

Vascular networks are critical for the development and maintenance of human tissues, as they support metabolism and regulate tissue growth and function. In vitro models such as organoids and organs-on-chip often have a limited capacity to recapitulate in vivo functional vascular networks and their integration within tissues. Most existing systems fail to mimic the structural and functional complexity of native capillary beds, lack physiological flow dynamics, and do not support vascular circulation. Here, we present a fully stem cell-derived microfluidic platform capable of generating perfusable vascular network organoids-on-chip with capillary-scale vessels, endothelial responses to biophysical forces, and physiologically accurate gene expression. Using this platform, we generate vascularized heart organoids-on-chip that replicate the dense capillary architecture of the heart and exhibit organ-specific vascular features and gene expression. These results establish a scalable and physiologically relevant approach for engineering and studying vascularized organoids under dynamic flow, with broad applications in developmental biology, disease modeling, and multi-organ in vitro systems.