Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro,ACS Biomaterials Science & Engineering

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Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-02-11 , DOI: 10.1021/acsbiomaterials.9b01837
Camilo Mora-Navarro _{1,

2} , Andreea Badileanu _{1,

2} , Ana M. Gracioso Martins _{1,

2} , Emily W. Ozpinar _{1,

2} , Lewis Gaffney _{1,

2} , Ian Huntress ₃ , Erin Harrell ₃ , Jeffrey R. Enders ₄ , Xinxia Peng _{3,

5} , Ryan C. Branski ₆ , Donald O. Freytes _{1,

2}

Affiliation

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 ACTA2 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.

中文翻译：

猪声带叠层固有蛋白生物材料调控TGF-β1介导的成纤维细胞体外活化。

声带固有层（VFLP）是声带（VF）的最外层之一，由组织特异性细胞外基质（ECM）蛋白组成，极易受到损伤。已经对各种生物材料进行了临床测试以治疗声音障碍（例如，水凝胶，脂肪和透明质酸），但VF功能的令人满意的恢复仍然遥遥无期。VF中的纤维化或瘢痕形成是一项重大挑战，因此需要开发和完善能促进VF愈合和正常功能的新型疗法。先前已经报道了衍生自天然组织的可注射水凝胶，其具有优于合成水凝胶的主要优点，包括建设性的组织重塑和减少的疤痕组织形成。这项研究旨在表征脱细胞的猪VFLP-ECM支架的组成以及VFLP-ECM衍生的水凝胶的细胞相容性和潜在的抗纤维化特性。此外，我们从VFLP-ECM中分离了潜在的基质结合囊泡（MBV）和大分子，它们也下调了平滑肌肌动蛋白在转化生长因子-β1（TGF-β1）刺激下的ACTAA2。该结果提供了VFLP-ECM的独特蛋白质组成以及VFLP-ECM的成分之间的潜在联系以及在转化为可注射形式时在体外观察到的TGF-β1信号抑制的潜在证据。

更新日期：2020-02-12

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