Abstract
<b>Background and aim:</b> Patients with end stage lung disease rely on mechanical ventilation (MV) to be able to breathe. However, MV often induces substantial lung injury known as ventilator-induced-lung-injury (VILI). Current in-vitro models of VILI fail to recapitulate the complex dynamic lung condition such as air-liquid interface (ALI) and 3D structures. To provide ALI conditions and customizable scaffolds for modelling VILI, we aimed to develop a lung-on-a-chip (LOC) device which allows for controllable stretch and is easily manufactured. <b>Methods and results:</b> We successfully fabricated a LOC using 3D printable molds and a commercially available porous membrane mimicking the lung ECM. This LOC was used to expose murine lung epithelial cells to stretch seen in MV (i.e. 25% cyclic strain). We observed higher nuclear translocation of the mechanosensors YAP/TAZ under stretched conditions (dynamic) compared to non-stretched conditions (static). Furthermore, confocal and scanning electron microscopy (SEM) images show higher amounts of cell loss in the dynamic condition compared to the static one. Cell death was measured using lactate dehydrogenase (LDH) levels in the supernatants where we confirmed higher levels of cell death under dynamic conditions compared to the static ones. <b>Conclusion:</b> Our study supports the potential use of 3D-printing as a fabrication technique for LOCs. Using the manufactured device, we were successfully able to accurately model lung injury on chip.
Published Version
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