Vascularizing organoids-on-chip for perfused and personalized models

Abstract

Organoids represent one of the most advanced in vitro models for studying human physiology, development and disease. Their potential is very important and they have broad applications, but their impact is currently limited by persistent challenges such as incomplete maturation, batch variability, restricted long-range interactions and, critically, the absence of functional and perfusable vasculature. Integrating organoids into microfluidic platforms offers a way to overcome some of these constraints by providing a controlled and dynamic microenvironment with precisely tuned physical and biochemical cues. Among emerging strategies, vascularization stands out as a critical step toward improving organoid physiology and relevance: establishing stable, lumenized and perfusable networks within the 3D structure enables direct delivery of oxygen and nutrients, facilitates metabolic waste removal and promotes their maturation beyond embryonic stages. Achieving such models will require the combined expertise of stem cell biology, microfluidics, and biomaterials engineering to generate devices with organ-specific endothelial and stromal components, physiological flow profiles, and bidirectional anastomosis between endogenous and exogenous vascular compartments. This review discusses the biological rationale, current strategies, and technical considerations for vascularizing organoids-on-chip, highlighting their potential to improve physiological relevance, functional performance, personalization and translational applicability.