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Objective: Fibrotic changes in the vocal fold mucosa have been observed in patients with vocal fold scarring, aged vocal fold, and sulcus vocalis, which often lead to severe voice disorders. Previous research suggests that the basic fibroblast growth factor (b FGF) improves variations in vocal fold properties [1,2]. Although clinical studies on b FGF treatments have been conducted [3,4,5], these studies only demonstrated the efficacy of this drug over a short period. The present study is the first to investigate the long-term efficacy of b FGF treatment., Methods: b FGF injections were performed in six patients from January of 2016 to December of 2017 at our institution. Patient follow-up continued for at least two years after the last injection. Three patients had vocal fold scarring, two had aged vocal fold atrophy, and one patient had sulcus vocalis. Each vocal fold was injected with 10 µg of b FGF four times. Voice and stroboscopic examinations were performed after surgery (at one month, three months, six months, one year, two years). Fundamental frequency, maximum phonation time (MPT), mean flow rate (MFR), amplitude perturbation quotient (APQ), pitch perturbation quotient (PPQ), and noise-to-harmonic ratio (NHR), and voice handicap index-10 (VHI-10) were examined and compared statistically between the pretreatment time and at each posttreatment time point., Results: The speaking F0 had an obvious decreasing tendency, with significant differences suggesting the increase in volume in the vocal folds. Aerodynamic parameters also showed small improvements. The most remarkable improvement was observed in the acoustic parameters, indicating that the treatment could improve the vocal fold to make vibrations symmetrically and regularly for a long period. Achievement of symmetry and regularity on vocal fold vibrations suggested the property changes had happened in the vocal folds. Consequently, the score of VHI-10 had improved, indicating high patient satisfaction with this treatment., Conclusion: b FGF injections could be a reliable treatment option for diseases that deteriorate the property of vocal fold., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives/hypothesis: Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet., Study Design: Animal experiment., Methods: Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA-bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high-speed camera, and histological analysis was performed., Results: The re-epithelialization process was delayed in the PGA and PGA-bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA-bFGF groups compared with the control group. The PGA-bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA-bFGF and control groups., Conclusions: The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects., Level of Evidence: NA Laryngoscope, 130:E436-E443, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Surgical management of cricoarytenoid joint (CAJ) ankylosis is challenging and has the risk of worsening voice quality. In the present case, augmentation surgery was performed on the cartilaginous portion of the vocal fold in a patient with CAJ ankylosis. A 24-year-old man sustained blunt trauma to the anterior neck three years prior to developing severe breathiness. Posterior glottal insufficiency resulting from lateral fixation of the right vocal fold was observed during phonation under laryngoscopy. In addition, electromyography and CT scan revealed severe ankylosis of the right CAJ. Type I thyroplasty performed on the right vocal fold did not improve postoperative vocal function. Therefore, augmentation surgery on the cartilaginous portion of the right vocal fold was performed via endolaryngeal microsurgery under general anesthesia with jet ventilation. A piece of temporalis fascia was autotransplanted into the submucosal space created at the posterior cartilaginous portion of the right vocal fold. This resulted in the narrowing of the posterior glottal gap during phonation, leading to improvement in hoarseness. Microsurgical management with autologous fascia augmentation of the cartilaginous portion of the vocal fold can be effective in patients with lateral vocal fold fixation due to CAJ ankylosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Scarred vocal folds result in irregular vibrations during phonation due to stiffness of the vocal fold mucosa. To date, a completely satisfactory corrective procedure has yet to be achieved. We hypothesize that a potential treatment option for this disease is to replace scarred vocal folds with organotypic mucosa. The purpose of this study is to regenerate vocal fold mucosa using a tissue-engineered structure with autologous oral mucosal cells., Study Design: Animal experiment using eight beagles (including three controls)., Methods: A 3 mm by 3 mm specimen of canine oral mucosa was surgically excised and divided into epithelial and subepithelial tissues. Epithelial cells and fibroblasts were isolated and cultured separately. The proliferated epithelial cells were co-cultured on oriented collagen gels containing the proliferated fibroblasts for an additional two weeks. The organotypic cultured tissues were transplanted to the mucosa-deficient vocal folds. Two months after transplantation, vocal fold vibrations and morphological characteristics were observed., Results: A tissue-engineered vocal fold mucosa, consisting of stratified epithelium and lamina propria, was successfully fabricated to closely resemble the normal layered vocal fold mucosa. Laryngeal stroboscopy revealed regular but slightly small mucosal waves at the transplanted site. Immunohistochemically, stratified epithelium expressed cytokeratin, and the distributed cells in the lamina propria expressed vimentin. Elastic Van Gieson staining revealed a decreased number of elastic fibers in the lamina propria of the transplanted site., Conclusion: The fabricated mucosa with autologous oral mucosal cells successfully restored the vocal fold mucosa. This reconstruction technique could offer substantial clinical advantages for treating intractable diseases such as scarring of the vocal folds.

Objectives: There is growing evidence that vocal fold stellate cells (VFSCs) in the human maculae flavae are tissue stem cells of the human vocal fold and that the maculae flavae are a stem cell niche. The origin of the cells in the human maculae flavae (CHMF) and the relationship with bone marrow-derived cells were investigated., Methods: Five human adult vocal fold mucosae were investigated. The CHMF were subcultured and morphological features were assessed. Immunoreactivity to antibodies directed to cytokeratin, desmin, GFAP, vimentin, CD34, CD45, and collagen type I was investigated., Results: Cultured CHMF formed a colony-forming unit, indicating they are mesenchymal stem cells or stromal stem cells in the bone marrow. The CHMF expressed hematopoietic markers (CD34, CD45) and collagen type I, which are the major makers for bone marrow-derived circulating fibrocytes. The cultured CHMF expressed epithelium-associated, muscle-associated, neural-associated, and mesenchymal cell-associated proteins, indicating the CHMF are undifferentiated and express proteins of all 3 germ layers., Conclusions: The CHMF are undifferentiated cells derived from the differentiation of bone marrow cells. The results of this study are consistent with the hypothesis that the VFSCs are tissue stem cells or progenitor cells of the human vocal fold mucosa., (© The Author(s) 2015.)