Self-assembled human arteriole-on-a-chip for arterial functionality testing and disease modeling.

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Microfluidics

Background:

• Existing vascular organ-on-a-chip models primarily focus on capillaries, with limited development of complex arterial structures.
• There is a need for advanced in vitro models to study human arterioles for drug development and disease modeling.

Purpose of the Study:

• To develop a physiological approach for creating self-assembled human arterioles in a microfluidic device.
• To establish a functional in vitro model for studying arteriogenesis and arterial thrombosis.

Main Methods:

• Utilized human umbilical artery endothelial cells (HUAECs) and smooth muscle cells (HUSMCs) for vasculogenesis and angiogenesis.
• Applied 1 Hz oscillating pressure to induce shear stress, promoting arteriogenesis.
• Cultured cells in a microfluidic device to form self-assembled arterioles with endothelium, smooth muscle, and basement membrane.

Main Results:

• Successfully developed self-assembled arterioles in vitro, featuring HUAEC endothelium wrapped by HUSMCs.
• Observed vessel network growth under high shear stress, with concurrent primary vessel enlargement and secondary vessel regression.
• Demonstrated functional vasodilation/vasoconstriction in response to dopamine and induced arterial thrombosis in the chip.

Conclusions:

• Cyclic shear flow is a critical physiological stimulus for arteriole development.
• The developed microfluidic arteriole model is functional and suitable for studying arterial thrombosis.
• This organ-on-a-chip system offers a viable in vitro platform for human arteriole research.