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Understanding the cellular responses based on low-density electrospun fiber networks
Biomaterials Advances ( IF 7.9 ) Pub Date : 2020-08-30 , DOI: 10.1016/j.msec.2020.111470
Han Tang , Bingcheng Yi , Xianliu Wang , Yanbing Shen , Yanzhong Zhang

Fibers produced from electrospinning are well-known to be extremely fine with diameters ranging from tens of nanometers to a few microns. Such ultrafine fibers not only allow for engineering scaffolds resembling the ultrastructure of the native extracellular matrix, but also offer possibility to explore the remodeling behavior of cells in vitro, due to their mechanically ‘adequate’ softness endowed by their ultrafine fineness. However, the remodeling effect of cells on the biomimicking fibrous substrates remains to be understood, because the crisscrossing and entangling among nanofibers in those tightly packed fibrous mats ultimately lead to merely a topological phenomenon, similar to that of the nanofiber-like topography embossed on the surface of a solid matter. In this study, the effect of nanofiber density on cellular response behavior was investigated by reducing the density of electrospun fiber networks. Using polycaprolactone (PCL) as a model polymer, randomly oriented fiber networks with various densities, namely, 37.7 ± 16.3 μg/cm2 (D1), 103.8 ± 16.3 μg/cm2 (D2), 198.2 ± 40.0 μg/cm2 (D3), and 471.8 ± 32.7 μg/cm2 (D4), were prepared by electrospinning for varied collection durations (10 s, 50 s, 100 s, and 10 min, respectively). By examining the responsive behavior of the human induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSCs) cultured on these nanofibrous networks, we showed that the fiber network with a moderate density (D2) is beneficial to the cell attachment, spreading, actin polymerization, contractility and migration. There also showed an increased tendency in nuclear localization of the Yes-associated protein (YAP) and subsequent activation of YAP responsive gene transcription, and cell proliferation and collagen synthesis were also enhanced on the D2. However, further increasing the fiber density (D3, D4) gave rise to weakened induction effect of fibers on the cellular responses. These results enrich our understanding on the effect of fiber density on cell behavior, and disclose the dependence of cellular responses on fiber density. This study paves the way to precisely design biomimetic fibrous scaffolds for achieving enhanced cell-scaffold interactions and tissue regeneration.



中文翻译:

了解基于低密度电纺纤维网络的细胞反应

众所周知,静电纺丝生产的纤维非常细,直径范围从几十纳米到几微米。这种超细纤维不仅允许工程支架类似于天然细胞外基质的超微结构,而且还提供了探索体外细胞重塑行为的可能性,由于其超细的细度赋予它们机械上“足够的”柔软度。然而,细胞对生物仿制纤维基质的重塑效果仍有待了解,因为那些紧密堆积的纤维垫中的纳米纤维之间的交叉和缠结最终仅导致一种拓扑现象,类似于浮雕在纤维上的纳米纤维状形貌。固体物质的表面。在这项研究中,通过降低电纺纤维网络的密度,研究了纳米纤维密度对细胞反应行为的影响。使用聚己内酯(PCL)作为模型聚合物,随机取向的纤维网络具有不同的密度,即37.7±16.3μg/ cm 2(D1),103.8±16.3μg/ cm 2(D2),198.2±40.0μg/ cm 2(D3)和471.8±32.7μg/ cm 2(D4)是通过静电纺丝在不同的收集时间(分别为10 s,50 s,100 s和10分钟)中制备的。通过检查在这些纳米纤维网络上培养的人诱导多能干细胞来源的间充质干细胞(hiPS-MSC)的响应行为,我们发现中等密度(D2)的纤维网络有益于细胞附着,扩散,肌动蛋白的聚合,收缩和迁移。还显示了Yes相关蛋白(YAP)的核定位和随后的YAP响应基因转录激活的增加趋势,并且在D2上细胞增殖和胶原合成也得到增强。然而,进一步增加纤维密度(D3,D4)导致纤维对细胞应答的诱导作用减弱。这些结果丰富了我们对纤维密度对细胞行为影响的理解,并揭示了细胞应答对纤维密度的依赖性。这项研究为精确设计仿生纤维支架铺平了道路,以实现增强的细胞支架相互作用和组织再生。

更新日期:2020-09-10
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