A Comparative Inflammation-on-a-Chip with a Complete 3D Interface: Pharmacological Applications in COPD-Induced Neutrophil Migration.

Abstract

Chronic obstructive pulmonary disease (COPD) is a slow-progressing inflammatory lung disease that is associated with high mortality and disability. There is a lack of appropriate preclinical models of COPD, which hampers drug discovery efforts. Herein, a comparative inflammation-on-a-chip (IoC) is developed with a complete 3D interface without the formation of any micropillar and phaseguide structures that replicated chemoattractant-induced neutrophil transendothelial migration (NTEM), a key feature of COPD. The IoC model is used to evaluate the pharmacological effects of CXCR2 inhibitors (MK-7123, AZD5069, and SB225002) on the migration of neutrophil-like cells in the presence of plasma samples from patients with COPD. This is the first study to evaluate inhibitors of CXCR2-dependent NTEM in a comparative IoC model that mimics the physiological 3D microenvironment, consisting of an endothelial barrier, extracellular compartment, and inflammatory conditions. This IoC model will be useful to investigate COPD severity using patient samples, and will aid basic and translational research involving NTEM.