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The efficacy of a novel collagen–gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar
Authors:Nao Hiwatashi  Shigeru Hirano  Masanobu Mizuta  Toshiki Kobayashi  Yoshitaka Kawai  Shin‐ichi Kanemaru  Tatsuo Nakamura  Juichi Ito  Katsuya Kawai  Shigehiko Suzuki
Institution:1. Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan;2. Department of Otolaryngology, Vanderbilt University, Nashville, TN, USA;3. Department of Otorhinolaryngology, Jikei University of Medicine, Tokyo, Japan;4. Department of Otolaryngology–Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan;5. Department of Bioartificial Organs, Institute for Frontier Medical Science, Kyoto University, Japan;6. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan
Abstract: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.
Keywords:vocal fold scar  collagen–  gelatin sponge  basic fibroblast growth factor  myofibroblast  scaffold  regeneration
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