Dual growth factor-immobilized bioactive injection material for enhanced treatment of glottal insufficiency
Dual growth factor-immobilized bioactive injection material for enhanced treatment of glottal insufficiency
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DOI：
10.1016/j.actbio.2018.12.047
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发表时间：
2019-03-01
影响因子：
9.7
通讯作者：
Kwon, Seong Keun
中科院分区：
文献类型：
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作者：
Choi, Young Hwan;Ahn, Hee-Jin;Kwon, Seong Keun
随着声门闭合不全治疗需求的增加，已经对几种注射材料进行了研究。然而，生物再吸收、注射材料的降解以及随后需要进行多次注射仍然是主要的临床问题。在这项研究中，我们制作了两种不同的生长因子（GF）[单一的碱性成纤维细胞生长因子（bFGF），单一的肝细胞生长因子（HGF），或双bFGF/HGF]固定聚己内酯（PCL）/普朗尼克F127微球。研究了这些材料作为生物活性注射喉成形剂的潜在用途。发现HGF在20天内连续释放，并且发现bFGF在25天内连续释放，如通过ELISA测定所证明的。人声带成纤维细胞（hVFFs）表现出显着更高的增殖能力的双重GF固定微球。将固定有生长因子的微球（bFGF、HGF和双GF）注射到新西兰白色兔麻痹的声带中。通过内窥镜观察和H&E染色，我们发现微球仍然定位在注射部位，导致瘫痪声带的恒定体积增加，4周后初始体积没有显著损失。双GF固定微球可上调声带细胞外基质（ECM）相关基因的表达。此外，双GF-固定微球抑制肌肉变性和成肌相关基因的上调。总之，双GF固定化微球被动地增加了瘫痪声带的体积，同时主动地诱导注射声带处的ECM合成并保留肌肉组织。双重固定化GF微球有望成为一种新的治疗声带麻痹的注射材料。在此，我们制造了聚己内酯（PCL）/普朗尼克F127微球，以增加瘫痪声带的体积。除此之外，我们还将生长因子（bFGF、HGF或双重bFGF/HGF）固定在这些微球的表面上。我们强调了双重GF固定化微球的功效，其被动地增加了麻痹声带的体积，在注射的声带处主动地诱导ECM合成并保存喉肌肉组织。我们的研究结果表明，双GF固定微球可能是一种新的注射材料，注射喉成形术治疗声带麻痹。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
With increasing demand for treatment of glottal insufficiency, several injection materials have been examined. However, biological resorption, degradation of injected materials, and the subsequent need to perform multiple injections still remain major clinical problems. In this study, we fabricated two different growth factor (GF) [single basic fibroblast growth factor (bFGF), single hepatocyte growth factor (HGF), or dual bFGF/HGF]-immobilized polycaprolactone (PCL)/Pluronic F127 microspheres. These materials were investigated for their potential use as bioactive injection laryngoplasty agents. HGF was found to be continuously released over 20 days and the bFGF was found to be continuously released over 25 days, as demonstrated by ELISA assay. Human vocal fold fibroblasts (hVFFs) showed significantly higher proliferative ability on dual GF-immobilized microspheres. GF-immobilized microspheres (bFGF, HGF, and dual GF) were injected into paralyzed vocal folds of New Zealand white rabbits. Through endoscopic observation and H&E staining, we identified that the microspheres remained localized at the injection site, resulting in constant volume augmentation of the paralyzed vocal fold without significant loss of the initial volume after 4 weeks. The expression of genes related to the extracellular matrix (ECM) in the vocal fold was upregulated by dual GF-immobilized microspheres. Furthermore, dual GF-immobilized microspheres inhibited muscle degeneration and upregulation of myogenic-related genes. In conclusion, dual GF-immobilized microspheres passively augmented the volume of the paralyzed vocal fold while actively inducing ECM synthesis at the injected vocal fold and preserving muscle tissue. Dual GF-immobilized microspheres could be a new and promising injection material for paralyzed vocal folds.Statement of SignificanceLimitation of prolonged augmentation of vocal fold and degeneration of vocal fold tissue still remain as major clinical problems in the treatment of vocal fold paralysis. Herein, we fabricated the polycaprolactone (PCL)/Pluronic F127 microspheres to augment volume of paralyzed vocal folds. On top of that, we additionally immobilized the growth factors (bFGF, HGF, or dual bFGF/HGF) on the surface of these microspheres. We highlight the efficacy of the dual GF-immobilized microspheres which augmented the volume of the paralyzed vocal fold passively, induced ECM synthesis actively at the injected vocal fold and preserved laryngeal muscle tissue. Our results suggest that the dual GF-immobilized microsphere could be a new promising injection material for injection laryngoplasty to treat paralyzed vocal fold. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.