MECHANICAL STRAIN INHIBITS REPAIR OF AIRWAY EPITHELIUM IN-VITRO

The repair of airway epithelium after injury is crucial in restoring e pithelial barrier integrity. Although the airway epithelium is stretch ed and compressed due to changes in both circumferential and longitudi nal dimensions during respiration and may be overdistended during mech anical ventilation, the effect of cyclic strain on the repair of epith elial wounds is unknown. Human and cat airway epithelial cells were cu ltured on flexible membranes, wounded by scraping with a metal spatula , and subjected to cyclic strain using the Flexercell Strain Unit. Bec ause the radial strain profile in the wells was nonuniform, we compare d closure in regions of elongation and compression within the same wel l. Both cyclic elongation and cyclic compression significantly slowed repair, with compression having the greatest effect. This attenuation was dependent upon the time of relaxation (TR) during the cycle. When wells were stretched at 10 cycles/min (6 s/cycle) with TR = 5 s, wound s closed similarly to wounds in static wells, whereas in wells with TR = 1 s, significant inhibition was observed. As the TR during cycles i ncreased (higher TR), wounds closed faster. We measured the effect of strain at various TRs on cell area and centroid-centroid distance (CD) as a measure of spreading and migration. While cell area and CD in st atic wells significantly increased over time, the area and CD of cells in the elongated regions did not change. Cells in compressed regions were significantly smaller, with significantly lower CD. Cell area and CD became progressively larger with increasing TR. These results sugg est that mechanical strain inhibits epithelial repair.