Optimization of Human Lung-Chip cultures to investigate effects of biomechanics on primary airway epithelial cell biology

With advances brought on by Organ-on-Chip technology, a new level of complexity was introduced into cell systems that allows research into human cellular cross-talk combined with mechanical cues. This added complexity is especially relevant in the lungs where biomechanics play a prominent role. Here we leveraged the commercial (EmulateTM) Lung-Chip and optimized its use for primary bronchial epithelial cell (PBEC) culturing to investigate the impact of airflow and mild stretch on epithelial biology. For this, PBEC culturing had to be optimized on a flexible PDMS, 7 µm pore-size membrane that allows application of stretch and leukocyte migration. To obtain a fully differentiated airway epithelium, cell media selection, coating strategy, and prevention of PBEC migration to the bottom channel was successfully achieved. Inter-chip variability (baseline IL-8 levels (ELISA)) was low (coefficient of variation