The efficacy of a novel collagen-gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar

被引:24
|
作者
Hiwatashi, Nao [1 ]
Hirano, Shigeru [1 ]
Mizuta, Masanobu [1 ,2 ]
Kobayashi, Toshiki [3 ]
Kawai, Yoshitaka [1 ]
Kanemaru, Shin-ichi [1 ,4 ]
Nakamura, Tatsuo [5 ]
Ito, Juichi [1 ]
Kawai, Katsuya [6 ]
Suzuki, Shigehiko [6 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Otolaryngol Head & Neck Surg, Kyoto, Japan
[2] Vanderbilt Univ, Dept Otolaryngol, Nashville, TN USA
[3] Jikei Univ Med, Dept Otorhinolaryngol, Tokyo, Japan
[4] Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Otolaryngol Head & Neck Surg, Osaka, Japan
[5] Kyoto Univ, Inst Frontier Med Sci, Dept Bioartificial Organs, Kyoto, Japan
[6] Kyoto Univ, Grad Sch Med, Dept Plast & Reconstruct Surg, Kyoto, Japan
关键词
vocal fold scar; collagen-gelatin sponge; basic fibroblast growth factor; myofibroblast; scaffold; regeneration; SUSTAINED-RELEASE; CANINE MODEL; HISTOLOGIC CHARACTERIZATION; EXTRACELLULAR-MATRIX; PALATAL MUCOSA; BONE-MARROW; CELLS; IMPLANTATION; BIOMECHANICS; CULTURE;
D O I
10.1002/term.2060
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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 alpha-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 mu g/cm(2); 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 (C) 2015 John Wiley & Sons, Ltd.
引用
收藏
页码:1598 / 1609
页数:12
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