A tissue-specific, injectable acellular gel for the treatment of chronic vocal fold scarring.
A tissue-specific, injectable acellular gel for the treatment of chronic vocal fold scarring.
复制标题
一种组织特异性、可注射的无细胞凝胶，用于治疗慢性声带疤痕。
DOI：
10.1016/j.actbio.2019.08.025
复制
发表时间：
2019
影响因子：
9.7
通讯作者：
Mau,Ted
中科院分区：
文献类型：
--
作者：
Xu,ChetC;Mau,Ted
基于凝胶的可注射生物材料具有治疗声带缺陷如瘢痕形成的显著潜力。理想的声带固有层修复注射剂应模拟固有层的微环境，以诱导无瘢痕伤口愈合和功能性组织再生。目前大多数合成或天然可注射生物材料不具有与天然声带固有层相同水平的复杂的组织特异性成分。在这项研究中，我们提出了一种新开发的注射凝胶制成的脱细胞牛声带固有层。Blyscan分析和质谱分析表明，声带特异性凝胶含有大量的硫酸化糖胺聚糖和超过250种蛋白质。Gene Ontology overrepresentation分析显示凝胶中的蛋白质主要促进抗纤维化的生物学过程。使用兔声带损伤模型的体内研究显示，可注射凝胶显著降低慢性瘢痕声带固有层的胶原密度和组织收缩。此外，这种无细胞凝胶在注射后仅引起最低限度的体液免疫反应。我们的研究结果表明，组织特异性，可注射的细胞外基质凝胶可能是一种有前途的生物材料，用于治疗声带瘢痕，即使在形成成熟的scar.Statement of SignificanceVocal fold propriate lamina scarring仍然是最重要的治疗挑战之一，在语音障碍患者的管理。手术切除疤痕可能会引起继发性疤痕，并产生不一致的结果。本研究报告了一种细胞外基质衍生的生物材料，其对声带固有层慢性瘢痕形成具有抗纤维化作用。它的可注射性最大限度地减少了递送过程的侵入性和粘膜侵犯的程度。在这项工作中，我们还描述了一种新的方法，它可以更准确地识别蛋白质的复杂混合物的脱细胞细胞外基质凝胶，排除干扰肽在凝胶制造过程中的酶消化。
Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process.In vivostudy using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar.Statement of SignificanceVocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.