Current organoid models lack functional vasculature, resulting in necrosis and limiting organoid size, maturation, and physiological relevance. Perfusion methods improve nutrient and oxygen supply somewhat, but long-term culture remains restricted, especially in metabolically active tissues like the brain. Co-culturing with endothelial cells often produces immature, non-perfusable vessels that fail to integrate fully with organoids. Existing approaches also neglect key mechanical and biochemical cues (shear stress and angiogenic factors), both critical for vessel stability but rarely combined. These limitations reduce organoid utility and translational relevance, highlighting the need for platforms that support dynamic, physiologically relevant vascularization.

This project aims to develop a modular vascularization-on-a-chip platform for co-culturing blood vessel organoids with other types, such as brain organoids, in a perfusable, chemically controlled environment. The system will enable precise control of vascularization dynamics through mechanical and biochemical cues, offering a scalable method to enhance in vitro organoid vascularization. The goal is to create physiologically relevant models for disease research, drug testing, and regenerative medicine.

We fabricated microfluidic chips with hydrodynamic organoid traps up to 800 µm wide. Blood vessel organoids were generated using established protocols and embedded in a collagen–Matrigel matrix inside the organoid traps. We are testing two vascular cell sources—HUVECs and dissociated blood vessel organoids—under varying platelet lysate concentrations to assess angiogenic responses. Shear stress is modulated by controlled perfusion to find optimal flow. Vascular development is evaluated through live imaging, perfusion testing, and staining for endothelial markers.

We successfully trapped and maintained blood vessel organoids within the microfluidic platform under continuous perfusion. Vascular cells remain viable in the collagen–Matrigel matrix, and platform stability under flow has been confirmed. We are currently investigating the effects of platelet lysate concentrations and shear stress on vascular cell behaviour, including endothelial organization, vessel formation, and permeability.

Our platform supports vascular cell culture under stable perfusion in a confined environment. These results provide a foundation for further studies on in vitro organoid vascularization. Future chip designs will facilitate vascularization of organoids through co-culture with blood vessel organoids, under optimized shear stress with biochemical stimulation to promote vessel formation.

This platform addresses a critical barrier limiting organoid size and function by supporting dynamic vascularization with physiological, mechanical, and biochemical cues. Planned chip enhancements aim to support functional vascular integration, advancing tissue engineering, disease modeling, and long-term clinical applications.