Fabrication and evaluation of an optimized acellular nerve allograft with multiple axial channels
Fabrication and evaluation of an optimized acellular nerve allograft with multiple axial channels
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具有多个轴向通道的优化脱细胞同种异体神经移植物的制作和评估
DOI：
10.1016/j.actbio.2020.07.059
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发表时间：
2020
影响因子：
9.7
通讯作者：
Ao Qiang
中科院分区：
文献类型：
--
作者：
Yu Tianhao;Wen Lili;He Jing;Xu Yingxi;Li Ting;Wang Weizuo;Ma Yizhan;Ahmad Muhammad Arslan;Tian Xiaohong;Fan Jun;Wang Xiaohong;Hagiwara Haruo;Ao Qiang
脱细胞同种异体神经移植是一种很有前途的替代自体神经移植的方法，但仍有许多缺点，这极大地限制了其疗效。在这里，我们开发了一个优化的脱细胞神经同种异体移植物与多轴向通道的改进的脱细胞方法。这些同种异体移植物被证实保留了更多的细胞外基质成分和因子，并有效地去除了细胞成分。同时，引入大通道和微通道来优化同种异体移植物的内部微观结构，这增加了孔隙率和吸水率，而没有显著的机械强度损失。体外实验表明，多通道同种异体移植物具有良好的促进雪旺细胞增殖和穿透的上级能力。此外，在体内实验中，使用多通道同种异体移植物桥接10 mm大鼠坐骨神经缺损。与传统的脱细胞同种异体移植物相比，它们表现出更好的引导再生神经纤维通过缺损段和恢复靶器官神经支配的能力，从而实现更好的肌肉和运动功能恢复。这些结果表明，这种多通道脱细胞神经同种异体移植物具有巨大的临床应用潜力，并为未来的神经再生研究提供了新的前景。重要性声明脱细胞神经同种异体移植物，保留天然细胞外基质，已被正式批准用于修复周围神经损伤在一些国家。然而，生物活性成分的损失和紧凑的内部结构导致传统的脱细胞同种异体移植物的临床效果不一。在本研究中，我们制作了一个优化的脱细胞神经同种异体移植物与多个轴向通道，这既可以使脱细胞容易地完成，并减少在制备过程中的洗涤剂的量。多通道脱细胞同种异体移植物的表征被证实具有更好的ECM生物活性分子和再生因子的保存。疗效评价显示，多通道同种异体移植物在体外可促进雪旺细胞在体内迁移，在体内可促进轴突再生和髓鞘形成，促进肌肉和运动功能的恢复。
Acellular nerve allografts are promising alternatives to autologous nerve grafts, but still have many drawbacks which greatly limit their curative effects. Here, we developed an optimized acellular nerve allograft with multiple axial channels by a modified decellularization method. These allografts were confirmed to preserve more extracellular matrix components and factors, and remove cellular components effectively. Meanwhile, macrochannels and microchannels were introduced to optimize internal microstructure of allografts, which increases porosity and water absorption, without significant loss of mechanical strength. Thein vitroexperiments demonstrated that the multichannel allografts showed superior ability of facilitating proliferation and penetration of Schwann cells. Additionally, in thein vivoexperiments, the multichannel allografts were used to bridge 10 mm rat sciatic nerve defects. They exhibited better capacity to guide regenerative nerve fibers through the defective segment and restore innervation of target organs, thus achieving better recovery of muscle and motor function, in comparison with conventional acellular allografts. These findings indicate that this multichannel acellular nerve allograft has great potential for clinical application and provides a new prospective for future investigations of nerve regeneration.Statement of SignificanceAcellular nerve allografts, with preservation of natural extracellular matrix, are officially approved to repair peripheral nerve injury in some countries. However, bioactive component loss and compact internal structure result in variable clinical effects of conventional acellular allografts. In the present study, we fabricated an optimized acellular nerve allograft with multiple axial channels, which could both enable decellularization to be easily accomplished and reduce the amount of detergents in the preparation process. Characterization of the multichannel acellular allografts was confirmed to have better preservation of ECM bioactive molecules and regenerative factors. Efficiency evaluation showed the multichannel allografts could facilitate Schwann cells to migrate inside themin vitro, and enhance regrowth and myelination of axons as well as recovery of muscle and motor functionin vivo.