Nanofibered Gelatin‐Based Nonwoven Elasticity Promotes Epithelial Histogenesis
Nanofibered Gelatin‐Based Nonwoven Elasticity Promotes Epithelial Histogenesis
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DOI：
10.1002/adhm.201700895
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发表时间：
2018-05
影响因子：
10
通讯作者：
Nicole Jedrusik;Christoph Meyen;G. Finkenzeller;G. Stark;S. Meskath;S. Schulz;T. Steinberg;P. Eberwein;S. Strassburg;P. Tomakidi
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文献类型：
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作者：
Nicole Jedrusik;Christoph Meyen;G. Finkenzeller;G. Stark;S. Meskath;S. Schulz;T. Steinberg;P. Eberwein;S. Strassburg;P. Tomakidi
关于组织再生，生物材料的力学变得越来越重要。因此，本研究报道了原位交联电纺丝明胶非织造垫（NWMs），其不同的弹性模量（ME）以分级的方式促进上皮组织的形成。NWMs由不同分布的纤维直径组成，产生的ME约为2.1、3.2和10.9 kPa。临床前体外验证的两步方法确定3.2 kPa的弹性优于其他组织发生上皮结果。因此，在没有间充质成纤维细胞和/或内皮细胞存在的情况下，这种3.2 kPa候选NWM被口腔黏膜上皮角质形成细胞定植。通过特定生物标志物的比色法和基于荧光的免疫组织化学（IHCH）来评估第1至10天上皮组织发生。其中包括指示上皮分化不同阶段的细胞角蛋白（CK） 14、CK1和天花素，以及作为增殖标志物的基底膜成分胶原IV型和Ki‐67。有趣的是，组织发生和IHCH揭示了NWM单独与天然上皮的最佳相似性，而不考虑其他对应细胞。这些发现证明了明胶NWM是一种方便的细胞基质，并且从临床应用的角度来看，NWM的机制对促进上皮组织发生是重要的。
Regarding tissue regeneration, mechanics of biomaterials gains progressive importance. Therefore, this study reports on in situ crosslinked electrospun gelatin nonwoven mats (NWMs) whose distinct modulus of elasticity (ME) promotes epithelial tissue formation in a graded manner. NWMs, comprising fiber diameters in various distributions, yield an ME of about 2.1, 3.2, and 10.9 kPa. A two‐step approach of preclinical in vitro validation identifies the elasticity of 3.2 kPa as superior to the other, regarding the histogenetic epithelial outcome. Hence, this 3.2 kPa candidate NWM is colonized with oral mucosal epithelial keratinocytes in the absence or presence of mesenchymal fibroblasts and/or endothelial cells. Evaluation of epithelial histogenesis at days 1 to 10 occurs by colorimetric and fluorescence‐based immunohistochemistry (IHCH) of specific biomarkers. These include cytokeratins (CK) 14, CK1, and involucrin that indicate different stages of epithelial differentiation, as well as the basement membrane constituent collagen type IV and Ki‐67 as a proliferation marker. Intriguingly, histogenesis and IHCH reveal the best resemblance of the native epithelium by the NWM alone, irrespective of other cell counterparts. These findings prove the gelatin NWM a convenient cell matrix, and evidence that NWM mechanics is important to promote epithelial histogenesis in view of prospective clinical applications.