Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature

Abstract

© The Royal Society of Chemistry 2021. Human organoids, self-organized and differentiated from homogenous pluripotent stem cells (PSC), replicate the key structural and functional characteristics of theirin vivocounterparts. Despite the rapid advancement of organoid technology and its diverse applications, major limitations in achieving trulyin vivolike functionality have been the lack of matured structural organization and constraints on tissue size, both of which are direct consequences of lacking a functional vasculature. In the absence of perfusable vessels, a core region within organoids quickly becomes necrotic during development due to increased metabolic demands that cannot be met by diffusion alone. Thus, incorporating functional vasculature in organoid models is indispensable for their growth in excess of several hundred microns and maturaturation beyond the embryonic and fetal phase. Here, we review recent advancements in vascularizing organoids and engineeringin vitrocapillary beds, and further explore strategies to integrate them on a microfluidic based platform, aiming for establishing perfused vasculature throughout organoidsin vitro.