Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York.
Department of Surgery, Division of Otolaryngology-Head & Neck Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
J Biomed Mater Res B Appl Biomater. 2018 Apr;106(3):1258-1267. doi: 10.1002/jbm.b.33936. Epub 2017 Jun 5.
Scarring of the vocal fold lamina propria can lead to debilitating voice disorders that can significantly impair quality of life. The reduced pliability of the scar tissue-which diminishes proper vocal fold vibratory efficiency-results in part from abnormal extracellular matrix (ECM) deposition by vocal fold fibroblasts (VFF) that have taken on a fibrotic phenotype. To address this issue, bioactive materials containing cytokines and/or growth factors may provide a platform to transition fibrotic VFF within the scarred tissue toward an anti-fibrotic phenotype, thereby improving the quality of ECM within the scar tissue. However, for such an approach to be most effective, the acute host response resulting from biomaterial insertion/injection likely also needs to be considered. The goal of the present work was to evaluate the anti-fibrotic and anti-inflammatory capacity of an injectable hydrogel containing tethered basic fibroblast growth factor (bFGF) in the dual context of scar and biomaterial-induced acute inflammation. An in vitro co-culture system was utilized containing both activated, fibrotic VFF and activated, pro-inflammatory macrophages (MΦ) within a 3D poly(ethylene glycol) diacrylate (PEGDA) hydrogel containing tethered bFGF. Following 72 h of culture, alterations in VFF and macrophage phenotype were evaluated relative to mono-culture and co-culture controls. In our co-culture system, bFGF reduced the production of fibrotic markers collagen type I, α smooth muscle actin, and biglycan by activated VFF and promoted wound-healing/anti-inflammatory marker expression in activated MΦ. Cumulatively, these data indicate that bFGF-containing hydrogels warrant further investigation for the treatment of vocal fold lamina propria scar. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1258-1267, 2018.
声带固有层的瘢痕形成可导致使人虚弱的嗓音障碍，从而显著降低生活质量。瘢痕组织柔韧性降低，从而降低了声带振动的效率，部分原因是声带成纤维细胞（VFF）产生了异常的细胞外基质（ECM）沉积，从而呈现出纤维化表型。为了解决这个问题，含有细胞因子和/或生长因子的生物活性材料可能为将瘢痕组织内的纤维化 VFF 转变为抗纤维化表型提供一个平台，从而改善瘢痕组织内 ECM 的质量。然而，为了使这种方法最有效，还需要考虑生物材料插入/注射引起的急性宿主反应。本研究的目的是评估一种含有固定化碱性成纤维细胞生长因子（bFGF）的可注射水凝胶在瘢痕和生物材料诱导的急性炎症双重背景下的抗纤维化和抗炎能力。使用一种包含激活的纤维化 VFF 和激活的促炎巨噬细胞（MΦ）的体外共培养系统，该系统位于一种含有固定化 bFGF 的 3D 聚乙二醇二丙烯酸酯（PEGDA）水凝胶中。培养 72 h 后，相对于单培养和共培养对照，评估了 VFF 和巨噬细胞表型的变化。在我们的共培养系统中，bFGF 降低了激活的 VFF 产生的纤维化标志物胶原 I 型、α平滑肌肌动蛋白和 biglycan 的水平，并促进了激活的 MΦ 中伤口愈合/抗炎标志物的表达。总之，这些数据表明，含 bFGF 的水凝胶值得进一步研究，以用于治疗声带固有层瘢痕。© 2017 Wiley Periodicals, Inc. J 生物材料研究杂志 B：应用生物材料，106B：1258-1267，2018。
