Modular 3D In Vitro Artery-Mimicking Multichannel System for Recapitulating Vascular Stenosis and Inflammation

Abstract

Inflammation and the immune response in atherosclerosis are complex processes involving local hemodynamics, the interaction of dysfunctional cells, and various pathological environments. Here, a modular multichannel system that mimics the human artery to demonstrate stenosis and inflammation and to study physical and chemical effects on biomimetic artery models is presented. Smooth muscle cells and endothelial cells were cocultured in the wrinkled surface in vivo-like circular channels to recapitulate the artery. An artery-mimicking multichannel module comprised four channels for the fabrication of coculture models and assigned various conditions for analysis to each model simultaneously. The manipulation became reproducible and stable through modularization, and each module could be replaced according to analytical purposes. A chamber module for culture was replaced with a microfluidic concentration gradient generator (CGG) module to achieve the cellular state of inflamed lesions by providing tumor necrosis factor (TNF)-α, in addition to the stenosis structure by tuning the channel geometry. Different TNF-α doses were administered in each channel by the CGG module to create functional inflammation models under various conditions. Through the tunable channel geometry and the microfluidic interfacing, this system has the potential to be used for further comprehensive research on vascular diseases such as atherosclerosis and thrombosis.