The efficacy of a novel collagen–gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar
Nao Hiwatashi
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorCorresponding Author
Shigeru Hirano
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Correspondence to:Shigeru. Hirano, Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: [email protected]Search for more papers by this authorMasanobu Mizuta
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Department of Otolaryngology, Vanderbilt University, Nashville, TN, USA
Search for more papers by this authorToshiki Kobayashi
Department of Otorhinolaryngology, Jikei University of Medicine, Tokyo, Japan
Search for more papers by this authorYoshitaka Kawai
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorShin-ichi Kanemaru
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Department of Otolaryngology–Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan
Search for more papers by this authorTatsuo Nakamura
Department of Bioartificial Organs, Institute for Frontier Medical Science, Kyoto University, Japan
Search for more papers by this authorJuichi Ito
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorKatsuya Kawai
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorShigehiko Suzuki
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorNao Hiwatashi
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorCorresponding Author
Shigeru Hirano
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Correspondence to:Shigeru. Hirano, Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: [email protected]Search for more papers by this authorMasanobu Mizuta
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Department of Otolaryngology, Vanderbilt University, Nashville, TN, USA
Search for more papers by this authorToshiki Kobayashi
Department of Otorhinolaryngology, Jikei University of Medicine, Tokyo, Japan
Search for more papers by this authorYoshitaka Kawai
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorShin-ichi Kanemaru
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Department of Otolaryngology–Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan
Search for more papers by this authorTatsuo Nakamura
Department of Bioartificial Organs, Institute for Frontier Medical Science, Kyoto University, Japan
Search for more papers by this authorJuichi Ito
Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorKatsuya Kawai
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorShigehiko Suzuki
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
Search for more papers by this authorAbstract
Vocal fold scar remains a therapeutic challenge. Basic fibroblast growth factor (bFGF) was reported to have regenerative effects for vocal fold scar, although it has the disadvantage of rapid absorption in vivo. A collagen–gelatin sponge (CGS) can compensate for the disadvantage by providing a sustained release system. The current study evaluated the efficacy of CGS combined with bFGF on vocal fold scar, using rat fibroblasts for an in vitro model and a canine in vivo model. We prepared fibroblasts from scarred vocal folds (sVFs) in rats and showed that bFGF accelerated cell proliferation and suppressed expression levels of cleaved caspase 3 and α-smooth muscle actin. Has 1, Has 3, Fgf2, Hgf and Vegfa mRNA levels were significantly upregulated, while Col1a1 and Col3a1 were dose-dependently downregulated, with a maximum effect at 100 ng/ml bFGF. In an in vivo assay, 6 weeks after lamina propria stripping, beagles were divided into three groups: CGS alone (CGS group); CGS with bFGF (7 µg/cm2; CGS + bFGF group); or a sham-treated group. Vibratory examination revealed that the glottal gap was significantly reduced in the bFGF group and the two implanted groups, whereas the CGS + bFGF group showed higher mucosal wave amplitude. Histological examination revealed significantly restored hyaluronic acid and elastin redistribution in the CGS + bFGF group and reductions in dense collagen deposition. These results provide evidence that CGS and bFGF combination therapy may have therapeutic potential and could be a promising tool for treating vocal fold scar. Copyright © 2015 John Wiley & Sons, Ltd.
Supporting Information
| Filename | Description |
|---|---|
| term2060-sup-0001-Supplementary.tifTIFF image, 584.9 KB | Results of vibratory examinations |
| term2060-sup-0002-Supplementary.tifTIFF image, 26.6 MB | Results of histological examinations |
| term2060-sup-0003-Supplementary.xlsxapplication/unknown, 11.2 KB | Time course of bFGF retention on collagen–gelatin sponge |
| term2060-sup-0004-Supplementary.xlsxapplication/unknown, 12.5 KB | Time course of endogenous bFGF levels |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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