Migration and Contraction of Fibroblasts from Normal and Scar Vocal Folds with Applications to Wound Healing

Abstract

Vocal fold scarring has various causes, including inflammation, trauma, radiotherapy and laryngeal surgeries. The treatment for vocal fold scarring is a challenge in Laryngology practice. Scars disrupt the layered structure and induce disorder in the lamina propria extracellular matrix, which causes significant change in vocal fold biomechanics, resulting in voice disorders that often compromise patient quality of life. Vocal fold fibroblasts are responsible for synthesis of the extracellular matrix, playing a key role in support of the lamina propria in normal and diseased conditions. During tissue injury, vocal fold fibroblasts become activated and differentiate into myofibroblasts, initiating contractile forces that facilitate wound healing. The correct balance between contraction and extracellular matrix deposition is required for optimal healing. Using a scratch assay with live-cell time lapse microscopy and traction force microscopy, we analyze the migration and contraction of fibroblasts from normal and scar human vocal folds during wound healing. As expected, most of the normal and scar vocal fold fibroblasts migrated toward the free area within 24 hours, which is a critical time-point after laryngeal surgeries. Scar vocal fold fibroblasts moved less persistently but in a collective manner whereas normal cells had more persistent and individual patterns of migration. Additionally, scar cells contracted approximately two times more than normal vocal fold fibroblasts. We expect these results to clarify mechanisms of migration and contraction of normal and scar vocal fold fibroblasts. This data may be useful to design experiments that increase or decrease contraction and migration to cause faster healing or reduced scar formation.