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The development of vascular networks on-chip is crucial for the long-term culture of three-dimensional cell aggregates such as organoids, spheroids, tumoroids, and tissue explants. Despite the rapid advancement of microvascular network systems and organoid technology, vascularizing organoids-on-chips remains a challenge in tissue engineering. Moreover, most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical settings to operate. Considering these constraints, we developed an innovative platform to establish and monitor the formation of endothelial networks around model spheroids of mesenchymal and endothelial cells as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 15 days on-chip. Importantly, these networks were functional, demonstrating intravascular perfusion within the spheroids or vascular organoids connected to neighbouring endothelial beds. This microphysiological system thus represents a viable organ-on-chip model to vascularize biological tissues and should allow to establish perfusion into organoids using advanced microfluidics.

Advances in microphysiological systems have prompted the need for robust and reliable cell culture devices. While microfluidic technology has made significant progress, devices often lack user-friendliness and are not designed to be industrialized on a large scale. Pancreatic islets are often being studied using microfluidic platforms in which the monitoring of fluxes is generally very limited, especially because the integration of valves to direct the flow is difficult to achieve. Considering these constraints, we present a thermoplastic manufactured microfluidic chip with an automated control of fluxes for the stimulation and secretion collection of pancreatic islet. The islet was directed toward precise locations through passive hydrodynamic trapping and both dynamic glucose stimulation and insulin harvesting were done automatically via a network of large deformation valves, directing the reagents and the pancreatic islet toward different pathways. This device we developed enables monitoring of insulin secretion from a single islet and can be adapted for the study of a wide variety of biological tissues and secretomes.