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猪声带固有层衍生生物材料在体外调节转化生长因子-β1介导的成纤维细胞活化。

Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro.

作者信息

Mora-Navarro Camilo, Badileanu Andreea, Gracioso Martins Ana M, Ozpinar Emily W, Gaffney Lewis, Huntress Ian, Harrell Erin, Enders Jeffrey R, Peng Xinxia, Branski Ryan C, Freytes Donald O

机构信息

Joint Department of Biomedical Engineering, North Carolina State University/ University of North Carolina-Chapel Hill, Raleigh, North Carolina 27695, United States.

Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina 27695, United States.

出版信息

ACS Biomater Sci Eng. 2020 Mar 9;6(3):1690-1703. doi: 10.1021/acsbiomaterials.9b01837. Epub 2020 Feb 11.

Abstract

The vocal fold lamina propria (VFLP), one of the outermost layers of the vocal fold (VF), is composed of tissue-specific extracellular matrix (ECM) proteins and is highly susceptible to injury. Various biomaterials have been clinically tested to treat voice disorders (e.g., hydrogels, fat, and hyaluronic acid), but satisfactory recovery of the VF functionality remains elusive. Fibrosis or scar formation in the VF is a major challenge, and the development and refinement of novel therapeutics that promote the healing and normal function of the VF are needed. Injectable hydrogels derived from native tissues have been previously reported with major advantages over synthetic hydrogels, including constructive tissue remodeling and reduced scar tissue formation. This study aims to characterize the composition of a decellularized porcine VFLP-ECM scaffold and the cytocompatibility and potential antifibrotic properties of a hydrogel derived from VFLP-ECM. In addition, we isolated potential matrix-bound vesicles (MBVs) and macromolecules from the VFLP-ECM that also downregulated smooth muscle actin under transforming growth factor-beta 1 (TGF-β1) stimulation. The results provide evidence of the unique protein composition of the VFLP-ECM and the potential link between the components of the VFLP-ECM and the inhibition of TGF-β1 signaling observed in vitro when transformed into injectable forms.

摘要

声带固有层(VFLP)是声带(VF)最外层之一,由组织特异性细胞外基质(ECM)蛋白组成,极易受到损伤。多种生物材料已在临床上用于治疗嗓音障碍(如,水凝胶、脂肪和透明质酸),但声带功能的满意恢复仍难以实现。声带纤维化或瘢痕形成是一个重大挑战,因此需要开发和完善促进声带愈合和正常功能的新型治疗方法。先前报道,源自天然组织的可注射水凝胶比合成水凝胶具有主要优势,包括促进组织重塑和减少瘢痕组织形成。本研究旨在表征去细胞猪VFLP-ECM支架的组成以及源自VFLP-ECM的水凝胶的细胞相容性和潜在抗纤维化特性。此外,我们从VFLP-ECM中分离出潜在的基质结合囊泡(MBV)和大分子,它们在转化生长因子-β1(TGF-β1)刺激下也下调平滑肌肌动蛋白。结果提供了VFLP-ECM独特蛋白质组成的证据,以及VFLP-ECM成分与体外转化为可注射形式时观察到的TGF-β1信号抑制之间的潜在联系。

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