Modelling immune cell migration in the lung using a microfluidic hydrogel barrier

Abstract

Acute lung injury (ALI) is a severe lung disease with a high morbidity and mortality, marked by inflammation of the lung. We developed a microfluidic system with a hydrogel barrier to study immune cell migration in ALI. A three-channel barrier-on-chip was designed and produced by soft lithography. The central channel is filled with hydrogel. Two adjacent channels, fluidically connected to the central channel, are aimed at creating an endothelial and an epithelial barrier. A chemotactic gradient was established across the hydrogel barrier by perfusing fMLP in the epithelial channel. Peripheral blood mononuclear cells (PBMCs) were perfused through the endothelial channel, as shown in figure 1. Migration was followed for 2 hours. Endothelial cells form a viable barrier alongside the hydrogel and the chemotactic gradient is stable. PBMCs crossing the endothelial barrier were quantified: more PBMCs cross the barrier when a chemoattractant is present, and these cells migrate further into the hydrogel. A novel barrier-on-chip system was developed. This model allows the study of immune cell migration under different conditions, such as different chemoattractant exposure or modification of the hydrogel barrier composition and stiffness.