Tracheal stenosis or granuloma is one of the most frequent complications after tracheostomy as a result of inflammatory, traumatic and fibrotic responses. Recently, multidisciplinary treatment has been used for tracheal stenosis and granuloma such as bronchoscopy, balloon dilation and tracheal surgeries. However, current treatments have risk of morbidity and may worsen the situation with high recurrence rate. The purpose of this study is to develop a novel combined treatment of photobiomodulation (PBM) and phlorotannin (PT) to prevent stenosis and granuloma formation after tracheal injury. The therapeutic effect of the combined treatment was evaluated on transforming growth factor (TGF)-beta-stimulated human tracheal fibroblasts and the developed tracheostomy rodent models. A 405 nm wavelength light was applied for PBM in a continuous-wave mode after treatment with Ecklonia cava-derived PT. MTT assay and western blot analysis showed that 12 J/cm2 of PBM and 100 µg/ml of PT were hardly cytotoxic (less than 20%). The combined treatment significantly inhibited cell migration and suppressed the expressions of alpha-smooth muscle actin and type-1 collagen via the downregulation of SMAD 2/3 and MAPK signaling pathways. Moreover, the proposed combined treatment showed promoted healing of tracheal fenestration wounds by modulating inflammation and overexpressed fibrotic activities on the developed tracheostomy rodent models. Therefore, the combination of PBM and PT demonstrates therapeutic potential for preventing tracheal stenosis and granuloma after tracheostomy.
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