Plasma is a mixture of electrons, ions, and energetic photons in the form of ionized gas that is generated when the gas is further energized. Non-thermal atmospheric plasma has several medical effects such as sterilization, anti-cancer, anti-inflammation, and tissue regeneration. However, the existing probe type is limited to local direct treatment. Therefore, we investigated the various effects using liquid type plasma to overcome this limitation. In addition, the therapeutic effects of non-thermal plasma treated solution (NTS) on upper airway mucosa have yet to be determined. In the first part, the effect of NTS on the regeneration of nasal mucosa was studied. Experiments were carried out using BEAS-2B, a human bronchial epithelial cell line similar to nasal mucosa epithelium. NTS had no cytotoxicity to the BEAS-2B cells and enhanced cell proliferation. NTS also promoted migration of BEAS-2B cells. NTS increased cell proliferation and migration via epidermal growth factor receptor activities and epithelial-to-mesenchymal transition signaling. Furthermore, NTS enhanced wound healing of nasal mucosa in an animal model. In the second part, the effect of NTS on the regeneration of vocal fold mucosa was examined. Migration and matrix metalloproteinase-2 expression of lipopolysaccharide (LPS)-treated human vocal fold-derived mesenchymal stem cells (VF-MSCs) were enhanced by NTS treatment. NTS treatment not only ameliorated nuclear factor-κB and interleukin-6 activation, induced by NTS treatment, but also the increased manifestation of α-smooth muscle actin and fibronectin, induced by transforming growth factor-ß. In a rabbit vocal fold scarring animal model, histological analyses showed increased hyaluronic acid deposition and decreased collagen accumulation after NTS injection. Videokymographic analysis showed more improved vibrations in NTS-treated vocal fold mucosa compared to those in non-treated group. The results of this study suggest that NTS may improve regeneration of the upper airway mucosa and improve functional remodeling following damage to the upper airway mucosa.
