Lung-on-a-chip composed of styrene-butadiene-styrene nano-fiber/porous PDMS composite membranes with cyclic triaxial stimulation

Abstract

The physiological function of lung is strongly correlated with its unique structural microenvironment and mechanical stimulation. Most existing lung-on-a-chips (LOCs) do not replicate the key physiological structure and stimulation of human lung, reducing their reliability in application. In this study, a scaffold structure of a styrene-butadiene-styrene (SBS) nanofiber and porous honeycomb polydime-thylsiloxane (PDMS) composite membrane was developed to construct an alveolar air-blood barrier that mimics the alveolar characteristics of flexibility, cross-scale structure, and triaxial mechanical stimulation. By combining micro-fluidic and electrospinning technology, a biomimetic LOC with dynamic triaxial cyclic strain was realized. The composite membrane had a Young’s modulus of 0.54 ± 0.05 MPa and was capable of 8–12% strain at 1 kPa air pressure. We monocultured and co-cultured human non-small cell lung cancer cells stably expressing red fluorescent protein (A549-RFP) with human umbilical vein endothelial cell stably expressing green fluorescent protein (HUVECs-GFP) within the chip. A multi-layered structure of epithelial cell layer-basal layer-endothelial cell layer, similar to the air-blood barrier in vivo, was constructed. The LOC was proved to be an initial foundation for creating in vitro alveolar physiological models, and could be a potential platform for application in physiology, pathology, toxicology, drug screening, and customized medicine.