Use of the 3DP scaffold coated with MSCs seeded in fibrin resulted in successful restoration of the shape and histology of the cervical oesophagus without any graft rejection; thus, this is a promising material for use as an artificial oesophagus.
Injection laryngoplasty is a widely used therapeutic option for drug delivery into vocal folds (VFs). Efficient injectable materials are urgently needed for treating intractable VF disease. Liquid-type non-thermal atmospheric plasma (LTP) has been found to be useful for various biological applications, including in regenerative medicine. We evaluated the effects of LTP on VF regeneration. Migration and matrix metalloproteinase-2 expression of lipopolysaccharide (LPS)-treated human vocal fold-derived mesenchymal stem cells (VF-MSCs) were enhanced by LTP treatment. LTP treatment not only ameliorated nuclear factor-κB and interleukin-6 activation, induced by LPS treatment, but also the increased manifestation of α-smooth muscle actin and fibronectin, induced by transforming growth factor-ß. In a rabbit VF scarring animal model, histological analyses showed increased hyaluronic acid deposition and decreased collagen accumulation after LTP injection. Videokymographic analysis showed more improved vibrations in LTP-treated VF mucosa compared to those in non-treated group. In conclusion, LTP treatment enhanced the recruitment and activation of VF-MSCs. Regulated extracellular matrix (ECM) synthesis and eventual functional improvement of scarred VFs were observed upon LTP treatment. The results of this study suggest that LTP injection can enhance wound healing and improve functional remodeling following VF injury. Impact statement Voice disorder has a significant impact on life quality, and one of the major causes of this voice disorder is vocal fold scarring. Therefore, various approaches have been tried to treat for voice disorder. However, no method has satisfied all requirements until now. Plasma medicine, which involves the medical application of plasma, is a rapidly developing field. We have confirmed that liquid-type plasma improved vocal fold scarring by mobilizing and activating vocal fold fibroblast. In conclusion, liquid-type plasma is a potential therapeutic agent for promoting vocal fold scarring through simple injection and it may be an alternative therapeutic agent for the current situation to treat voice disorder.
An in situ-forming gel system comprised of diblock copolymer formed from polyethylene glycol (PEG) and polycaprolactone (PCL) {MPEG-b-(PCL-ran-PLLA)} could be used in controlled drug delivery for tissue remodeling. The purpose of this study is to demonstrate favorable vocal folds (VF) regeneration by using MPEG-b-(PCL-ran-PLLA) diblock copolymers (C97L3; CL/LA ratio 97:3) incorporating hepatocyte growth factor (HGF). Gradual release of HGF from C97L3 is detected and biochemical properties of released HGF are maintained. A scar is made with microscissors on both VFs in 32 rabbits, followed by injection of HGF-only, C97L3-only, or HGF-C97L3 composite gel in the left side VF, while the right side VF is left untreated. In vivo fluorescence live imaging system demonstrates that C97L3 enables the sustained release of injected HGF in the scarred VF for 12 weeks. The histological analysis shows increased glycosaminoglycan including hyaluronic acid accumulation and decreased collagen deposition. Videokymographic analysis shows more favorable vibrations of HGF-C97L3 treated VF mucosa, compared to other treatment groups. In conclusion, the controlled HGF release helps to regulate extracellular matrix synthesis, and leads to the eventual functional improvement of the scarred VF.
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