纺织学报 ›› 2023, Vol. 44 ›› Issue (11): 232-239.doi: 10.13475/j.fzxb.20220607302

• 综合述评 • 上一篇    下一篇

碳纳米管掺杂高聚物制备人工神经导管的研究进展

宋功吉1, 王煜煜1, 王善龙1, 王建南1,2, 许建梅1,2()   

  1. 1.苏州大学 纺织与服装工程学院, 江苏 苏州 215021
    2.苏州大学 纺织行业医疗健康用蚕丝制品重点实验室, 江苏 苏州 215127
  • 收稿日期:2022-06-30 修回日期:2022-11-17 出版日期:2023-11-15 发布日期:2023-12-25
  • 通讯作者: 许建梅(1976—),女,副教授,博士。主要研究方向为生物材料。E-mail:xujianmei@suda.edu.cn。
  • 作者简介:宋功吉(1998—),男,硕士生。主要研究方向为导电性人工神经导管的制备。
  • 基金资助:
    纺织行业医疗健康用蚕丝制品重点实验室项目(Q811580321)

Research progress in artificial nerve conduit prepared by carbon nanotube-doped polymer

SONG Gongji1, WANG Yuyu1, WANG Shanlong1, WANG Jiannan1,2, XU Jianmei1,2()   

  1. 1. College of Textile and Clothing Engineering, Soochow University, Suzhou, Jiangsu 215021, China
    2. Key Laboratory of Textile Industry for Silk Products in Medical and Health Use, Soochow University, Suzhou, Jiangsu 215127, China
  • Received:2022-06-30 Revised:2022-11-17 Published:2023-11-15 Online:2023-12-25

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摘要：

为促进碳纳米管在修复神经损伤中的应用,以碳纳米管掺杂的纺织高聚物材料制备导电性人工神经导管的相关研究为基础,分析了碳纳米管的纳米形貌和导电性能在促进神经再生中的作用,概述了碳纳米管表面改性的作用与方法,综述了碳纳米管的生物医学应用、复合碳纳米管高聚物制备导电性人工神经导管的方法以及其神经再生效果。最后指出:碳纳米管用于制备导电性人工神经导管时应使其与生物体组织作用的界面保持纳米形貌;碳纳米管进行功能化改性后更有利于受损神经的再生与修复;应关注复合碳纳米管制备的神经导管在降解过程中可能带来的体内代谢毒性;碳纳米管掺杂高聚物在导电性神经导管的制备中具有突出的优势与广阔的应用前景。

关键词: 高聚物, 碳纳米管, 导电性, 人工神经导管, 纳米形貌

Abstract:

Significance Currently, peripheral nerve injury causes great distress to patients, and artificial nerve conduits are used to replace autologous nerve grafting as an ideal treatment option. In the process of peripheral nerve injury and repair, the synergistic effect of conductive nerve conduits and electrical stimulation can greatly accelerate the regeneration and recovery of injured nerves, but polymers suitable for conduit formation are largely nonconductive. Thus, many studies prepare conductive artificial nerve conduits by adding conductive materials, such as carbon nanotubes (CNT), polypyrrole (PPy), and polyaniline (PANI), to the natural or synthetic polymers. Among the conductive materials, CNT has attracted much attention because of their better biocompatibility and excellent electrical conductivity. This review focuses on the physiochemical properties of CNT, their mechanisms for nerve repair and regeneration, the chemical modification of CNT and the formation methods of conductive nerve conduits, to better understand the nerve regeneration mechanism of CNT and clarifies the key progress and difficulties in preparing CNT-composited nerve conduits, hoping provide a beneficial reference for the preparation and application of carbon nanotubes in conductive nerve conduits.

Progress The use of CNT for conductive nerve conduits has been mainly achieved by the doping of CNT with various types of natural or synthetic polymers. Current research mainly focuses on four aspects. The first is the exploration of the role and mechanism of the physiochemical properties of CNT in nerve regeneration. The morphological structure of CNT resembles that of neurites, and the microenvironment constructed by its nanotopography provides structural guidance for the adhesion and extension of neurons. Its anisotropic conductivity is also like that of neurons, and electrical coupling between CNT and neurons facilitates neural signal transmission. The second is the study of various modification methods of CNT to improve its biocompatibility and processability. The modified CNT, with improved water solubility, shows better biocompatibility. Researchers adopted positively and negatively charged particles, polymers, growth factors, etc., to biofunctionalize CNT by covalent and noncovalent methods. Through functionalization, it is easier to interact with nerve cells and avoid agglomeration in vivo, which is beneficial for cellular uptake and internalization and in vivo degradation of nerve conduits. The third is the study of the forming methods of nerve conduits from CNT-doped polymers. The textile processing methods commonly used for conductive artificial nerve conduits include electrospinning techniques, 3D printing techniques, solution casting and braiding. In addition, polymers and CNT can be combined by coating, crosslinking, and so on. The fourth is the investigation on the biological characteristics and applications of conductive nerve conduits. It is believed that nerve repair is better with conductivity of 10-4~10-3 S/m, and this range, higher conductivity results in better nerve regeneration because the conductive film can improve functional recovery and myelination of the regenerated nerve fibers.

Conclusion and Prospect Through the analysis and review of the relevant research on the preparation of conductive artificial nerve conduits from CNT-composited polymers, the following conclusions can be drawn. 1) CNT has unique advantages in nerve repair and regeneration by virtue of its unique nanomorphology and excellent conductivity. The nanotopography of CNT facilitates its creation of an extracellular matrix-like environment when compositing with polymer materials, thereby promoting neuronal adherent growth and inducing nerve regeneration. Its excellent electrical conductivity significantly improves the efficiency of nerve signal transmission, and paired with external electrical stimulation, it can better repair and regenerate the injured nerve. 2) The functionalization modification of CNT can significantly improve its water solubility, which makes the fabrication and processing of composite conductive artificial neural conduits more convenient, and its biological toxicity is further reduced. 3) CNT and polymers can be combined by blending, coating, or crosslinking in many different ways, and the fabricated conductive artificial nerve conduits have achieved better nerve regeneration effects in animal experiments. At present, the use of CNT for conductive artificial nerve catheters has become a hotspot, but the possible biological metabolic toxicity and long-term toxicity caused by the added amount of CNT as well as the degradation speed of the nerve conduits are less studied. The mechanisms, methods, and influences of synergistic effects between CNT and electrical stimulation in vitro require further study, especially in addition to the nanotopography, electrical conductivity of CNT in catheter preparation, the structure of the catheter, and polymer characteristics, etc., which should be comprehensively considered to achieve the final product with excellent neurorestorative effects in animal experiments or clinical applications.

Key words: high polymer, carbon nanotube, conductivity, artificial nerve conduit, nanomorphology

中图分类号: 

  • TS101.4

图1

碳纳米管的表面功能化"

图2

导电性神经导管支架的制备 注:BAPO—苯基双 (2,4,6-三甲基苯甲酰基)氧化膦;PGF—磷酸盐玻璃微纤维。"

表1

掺杂碳纳米管的导电性人工神经导管的再生效果"

复合材料 CNT表面
改性		 导管制备
方法		 导管结构 电学性能 体外细胞培养 神经再生实验 参考文献
SF/SWCNT/
FN		 — 模具法/冷冻干燥 导管呈高度多孔结构,纤连蛋白纤维(FN)排列在衬底上 电导率为
2.1×10-3 S/m		 人脑胶质母细胞瘤:培养7和14 d,增殖显著 植入5周后,轴突再生,大鼠坐骨神经被成功桥接,功能恢复,但恢复的不完全 [23]
CNT/PGF/
PLDLA		 胺基化 浸涂方式与共价结合 导管内填充平行排列的纳米纤维,部分含CNT 电导率为
10-3~10-4 S/m		 PC12细胞:3 d后CNT-PGF浸提液中的细胞存活率明显高于其它浸提液,细胞数量随浸提液浓度的提高而增加。大鼠背根神经节细胞:3 d后神经突起在超细纤维基质上定向延伸,且含有CNT的延伸更长 植入16周后,轴突再生,再生肌肉组织的横截面积和电生理结果均得到显著改善 [6]
胶原蛋白/
PCL/MWNTs		 羧基功能化 MWNTs增
强型静电纺丝悬浮液		 管状结构,长度分布较宽,MWCNTs直径在20~50 nm之间 — 雪旺细胞:3 d后细胞有效黏附,且轴突明显伸长,MWCNTs的加入有助于神经电信号传导 术后4个月,植入的神经与神经残端组织完全融合,神经外膜上有丰富的毛细血管,未观察到炎症反应 [25]
PEGDA/
MWNTs		 胺功
能化		 共混、可印刷生物油墨 可调孔结构、
CNT分散
均匀		 充电容量为(2.21 ±0.12)mC/cm2,显著高于不含MWCNTs的导管 小鼠神经外胚层神经干细胞:8 d后有效增殖分化,0.1%的MWCNTs支架轴突生长最长 — [35]
PCLF/
MWCNTs		 — 超声波搅拌共混和光交联法 CNT束逐层
分散在
PCLF中		 电化学工作站交流电测试,加入MWCNTs得到较低电阻 鼠嗜铬细胞瘤细胞:5 d后神经元分化、轴突生长,电
刺激进一步促进了细胞增殖、细胞迁移和细胞内连接的形成		 — [36]
PET/
MWCNTs		 — MWNTs/明胶悬浮液涂覆 微孔三维支架,MWCNTs包覆在PET基质表面 — 小鼠胚胎干细胞:2周后活力显著提高,并大量增殖,神经元高度分化 — [37]
PVA/
MWCNTs		 羧基功能化 混合溶液、冷冻/解冻循环 — 电导率为
5.79 ×10-4 S/m		 — 术后12周,大鼠坐骨神经纤维成功再生,功能恢复到正常水平 [38]
SWCNTs/
鼠尾I 型胶原		 — 超声波共混、 烘干成膜 — 电导率为
0.070 9~1.73 S/m		 胚胎大鼠神经干细胞:3 d后1 mg/mL的SWCNT数量明显提高,长度伸长;7 d后自发地向神经元分化 — [39]
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