Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin nanofiber hydrogel
Prompt peripheral nerve regeneration induced by a hierarchically aligned fibrin nanofiber hydrogel
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DOI：
10.1016/j.actbio.2017.04.010
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发表时间：
2017-06-01
影响因子：
9.7
通讯作者：
Wang, Xiumei
中科院分区：
文献类型：
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作者：
Du, Jinrong;Liu, Jianheng;Wang, Xiumei
纤维蛋白在周围神经再生中起着至关重要的作用，它可以在神经再生的初始阶段以纵向纤维蛋白索的形式自发地发生。纤维蛋白索可引导雪旺细胞迁移、增殖和轴突再生，对神经再生具有重要意义。在本研究中，我们通过静电纺丝和分子自组装制备了一种三维分层排列的纤维蛋白水凝胶（AFG），以模拟天然纤维蛋白电缆的结构和生物学功能。AFG显示出与神经细胞外基质（ECM）和天然纤维蛋白电缆相似的分层排列的拓扑结构以及低弹性（类似于1.5 kPa）。在体外培养条件下，观察到雪旺细胞（SC）和背根神经节的快速、定向的细胞粘附和迁移。然后，AFG被用作生物工程壳聚糖管中的潜在管腔内基质，以桥接大鼠坐骨神经10 mm长的间隙。我们发现，AFG作为一个有益的微环境，支持SC电缆的形成和轴突再生2周内。在AFG植入12周后进行进一步的组织学和形态学分析以及电生理和功能检查。形态学分析和电生理检查结果表明，我们开发的移植物的再生效果接近自体神经移植物，但上级空心壳聚糖管（hCST）和随机纤维蛋白可降解水凝胶（RFG）。我们的研究结果表明，AFG通过模仿天然纤维蛋白索以及神经ECM的定向和柔软特征来创造有益的微环境，以加速轴突再生，从而显示出在神经再生中应用的巨大潜力。已经提出了多种策略来制备具有更复杂结构的功能化神经引导导管（NGC），以获得最佳的修复效果。据报道，在空的NGC中，在周围神经再生的初始阶段自发地形成纵向定向的纤维蛋白缆，其可以指导雪旺细胞的迁移和增殖，并促进轴突再生。因此，基于仿生学的思想，我们通过静电纺丝和分子自组装制备了一种三维分层排列的纤维蛋白凝胶（AFG），类似于天然纤维蛋白电缆的结构和生物学功能，并作为管腔内填充物，以加速轴突再生。我们发现，AFG是一个有益的微环境，以支持SC电缆的形成和加速轴突再生，改善运动功能的恢复。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Fibrin plays a crucial role in peripheral nerve regeneration, which could occur spontaneously in the format of longitudinally oriented fibrin cables during the initial stage of nerve regeneration. This fibrin cable can direct migration and proliferation of Schwann cells and axonal regrowth, which is very important to nerve regeneration. In the present study, we prepared a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) through electrospinning and molecular self-assembly to resemble the architecture and biological function of the native fibrin cable. The AFG displayed a hierarchically aligned topography as well as low elasticity (similar to 1.5 kPa) that were similar to nerve extracellular matrix (ECM) and the native fibrin cable. Rapid, directional cell adhesion and migration of Schwann cells (SCs) and dorsal root ganglions were observed in vitro. The AFG was then used as a potential intraluminal substrate in a bio-engineered chitosan tube to bridge a 10-mm-long sciatic nerve gap in rats. We found that the AFG served as a beneficial microenvironment to support SCs cable formation and axonal regrowth within 2 weeks. Further histological and morphological analyses as well as electrophysiological and functional examinations were performed after AFG implantation for up to 12 weeks. The results from morphological analysis and electrophysiological examination indicated that regenerative outcomes achieved by our developed graft were close to those by an autologous nerve graft, but superior to those by hollow chitosan tubes (hCST) and random fibrin nanofiber hydrogel (RFG). Our results demonstrate that the AFG creates an instructive microenvironment by mimicking the native fibrin cable as well as the oriented and soft features of nerve ECM to accelerate axonal regrowth, thus showing great promising potential for applications in neural regeneration.Statement of SignificanceIn peripheral nervous system defect repair, a wide variety of strategies have been proposed for preparing functionalized nerve guidance conduits (NGC) with more complex configurations to obtain optimal repair effects. Longitudinally oriented fibrin cables were reported to form spontaneously during the initial stages of peripheral nerve regeneration in an empty NGC, which can direct the migration and proliferation of Schwann cells and promote axonal regrowth. Therefore, based on the biomimetic idea, we prepared a three-dimensional hierarchically aligned fibrin nanofiber hydrogel (AFG) through electrospinning and molecular self-assembly, resembling the architecture and biological function of the native fibrin cable and serving as an intraluminal filling to accelerate axon regeneration. We found that the AFG was a beneficial microenvironment to support SCs cable formation and accelerate axonal regrowth with improved motor functional recovery. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.