An automated microfluidic platform integrating functional vascularized organoids-on-chip

Abstract

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.

Blood Vessel Organoids for Development and Disease

“…To tackle the lack of controllable perfusion, we are currently working on a microfluidic approach for vascular organoids. 43 An analysis of flow and shear rates revealed values comparable to those observed in human capillaries, thus allowing us to further refine the vascular organoid model. 43 As a next step, it would be interesting to study how altered pressure influences vessel remodeling, EC characteristics, or mural cell composition.…”

“…41,42 Integration into microfluidic systems allows for perfusion of the vessels. 43 Implant of the organoids into immunodeficient mice can be performed to achieve larger vessels and a fully perfused human vascular tree, but throughput is low. 42 Illustration credit: Sceyence Studios.…”

“…Self-organizing blood vessel organoids (BVOs) capture both vasculogenesis and angiogenesis 41,42. Integration into microfluidic systems allows for perfusion of the vessels 43. Implant of the organoids into immunodeficient mice can be performed to achieve larger vessels and a fully perfused human vascular tree, but throughput is low 42.…”

Fusion of blood vessel organoids with human pancreatic islets improves insulin response over time

“…Interestingly, BVOs have also been shown to enable perfusion into an organ-on-chip model 20 , highlighting the tremendous possibilities of disease modeling using both the fusion and perfusion capacities of BVOs.…”

Microfluidics and Organoids, the Power Couple of Developmental Biology and Oncology Studies

“…While PDMS and 3D printed devices have proven to be an ideal solution for fast cost-effective prototyping and proof of concept scenarios, they are not always applicable outside of a research lab due to both material properties and manufacturing limitations [ 20 , 61 , 62 , 63 ]. There are alternative materials that are accompanied by alternative fabrication methods.…”