纺织学报 ›› 2025, Vol. 46 ›› Issue (03): 236-244.doi: 10.13475/j.fzxb.20240404702

• 综合述评 • 上一篇    下一篇

纳米纤维在人工神经导管中的应用与研究进展

陆宁1, 陈碧泠1, 宋功吉1, 罗忆心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:2024-04-18 修回日期:2024-08-12 出版日期:2025-03-15 发布日期:2025-04-16
  • 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:陆宁(1999—),女,硕士生。主要研究方向为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)

Application and research progress of nanofibres in artificial nerve conduits

LU Ning1, CHEN Biling1, SONG Gongji1, LUO Yixin1, 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:2024-04-18 Revised:2024-08-12 Published:2025-03-15 Online:2025-04-16

摘要:

为探讨纳米纤维在神经再生修复中的作用,开发出纳米纤维基神经导管,分析了纳米纤维对周围神经损伤修复的再生机制,探讨了不同材料在纳米纤维基神经导管中的作用与应用,综述了纳米纤维制备的方法及相应的纳米纤维基神经导管的制备方法,讨论了纳米纤维基神经导管的不同内部结构。最后指出:纳米纤维基神经导管制备应考虑宏量化、标准化制备方法;从结构仿生与功能仿生的角度,去构筑组织与材料相接触的纳米仿生界面,包括:仿细胞外基质环境、微图案纳米尺度仿生界面、多尺度分级有序的微纳米仿生界面;将多种修复机制结合,发挥协同增效作用,可实现长距离神经损伤的修复。

关键词: 纳米纤维, 静电纺丝, 神经导管, 神经损伤, 机械分纤

Abstract:

Significance In recent years, artificial nerve conduits have shown promising applications in the repair of peripheral nerve injuries. By controlling the materials, structure, and surface morphology of neural conduits, they are expected to replace autologous nerve grafts. Especially, nanofiber-based nerve conduits have become a research focus in the repair of peripheral nerve injuries. Nanofibers are characterized by small diameter, long length and large specific surface area. Artificial nerve conduits prepared from them can more effectively mimic the structure of the extracellular matrix, well promoting cell adhesion, proliferation, and differentiation, guiding the growth of neuronal axons, and accelerating the repair and regeneration of damaged nerves. Therefore, analyzing the regenerative repair mechanisms of nanofiber-based nerve conduits, reviewing the materials and methods for preparing nanofiber-based nerve conduits, as well as different structures, will provide a reference for the development and application of nanofiber-based nerve conduits in peripheral injury repair.

Progress Currently, research on nanofiber-based nerve conduits mainly focuses on four aspects. The first is the investigation of the role and mechanism of nanofibers in nerve regeneration and repair. It is believed that the high surface area-to-volume ratio of nanofibers can enhance cell contact area, while their high porosity ensures the supply of oxygen and nutrients, thus more effectively inducing cell growth and tissue regeneration. The second aspect is on the exploration of natural or synthetic polymer materials with excellent biocompatibility and biodegradability, which are easy to prepare into nanofiber-based nerve conduits. The third is about the preparation methods of nanofiber-based nerve conduits. This study summarizes four commonly used preparation methods for nanofiber-based neural conduits: electrospinning, mechanical drawing, phase separation, and self-assembly. Among them, electrospinning is the most commonly used method. This approach involves either first producing a nanofiber mat and then rolling it to form a conduit, or directly spraying nanofibers onto the surface of a cylindrical core tube and then demolding to form the conduit. Additionally, in the electrospinning process, conductive polymers or conductive media can be added to prepare nanofibers with conductivity. Furthermore, nutrients, functional proteins, and bioactive molecules can be incorporated to promote the adhesion and proliferation of nerve cells. The fourth aspect is on the structure of nanofiber-based nerve conduits. Multi-channel structures can guide axonal regeneration directionally; filling the conduit with micro/nanofibers can guide the directional growth of nerve cells and accelerate the formation of the extracellular matrix environment within the conduit; filling the conduit with aligned nanofiber sponge provides a simulated three-dimensional extracellular matrix environment for cell adhesion, growth, and migration.

Conclusion and Prospect By analyzing and reviewing relevant research on nanofiber-based artificial nerve conduits, the following conclusions are drawn. 1) Owing to unique structural advantages, nanofibers can better guide cell adhesion and migration, promote cell growth, and are more conducive to the repair of peripheral nerve injuries. 2) Various methods such as electrospinning, self-assembly, and phase separation can be employed to prepare natural polymer materials, synthetic polymer materials, and composite materials into nanofiber-based nerve conduits with special structures, physical, and biological properties. 3) Oriented nanofiber-based nerve conduits can guide the directional growth of neuronal axons, providing a macroscopic guiding effect for nerve growth. Nanofiber-filled nerve conduits can provide a 3-D extracellular matrix microenvironment for cell adhesion and proliferation, guiding axonal regeneration.

Currently, electrospinning technology remains the primary method for preparing nanofiber-based artificial nerve conduits. This process involves producing nanofiber membranes through electrospinning, which are subsequently formed into conduits. However, there is a lack of standardization in the conduit formation process, resulting in significant variations between batches. Future research trends in the preparation of nanofiber-based nerve conduits may focus on standardization and large-scale manufacturing. Additionally, there may be a shift towards constructing biomimetic interfaces for tissue-material interaction, incorporating functional biomimicry and structural biomimicry perspectives.

Key words: nanofiber, electrospinning, nerve guidance conduit, nerve injury, mechanical fiber splitting

中图分类号: 

  • TS101.4

表1

纳米纤维基神经导管"

导管材料 导管结构 制备方法 纳米纤维平均直径/nm 生物相容性评价 神经修复体内评价
丝素蛋白[21] 中空
(随机)
静电纺丝 290 种植4 d后,SCs在纳米SF纤维膜上迅速增殖;7 d后覆盖整个膜 10周时,大鼠坐骨神经运动功能显著提高且管内充满再生轴突神经丝和髓鞘碱性蛋白
壳聚糖[22] 中空
(取向)
静电纺丝 400 SCs在取向纳米纤维上沿同一方向排列 20周后,大鼠坐骨神经感觉和运动功能恢复;30周后,取向纤维轴突数量及直径大于非取向
PLLA[23] 中空
(取向)
静电纺丝 300 NSC伸长方向及其神经突生长方向与纤维方向平行
PCL[24] 多通道 静电纺丝 850 ± 220 植入大鼠坐骨神经,4周时多通道导管的SFI和髓鞘轴突数量大于空心管。
PLGA/
PCL[25]
中空 静电纺丝 280~8 000 用于大鼠坐骨神经缺损修复时,诱导了神经再生和2条切断的坐骨神经束的功能性连接
PLLA[26] 多通道 相分离 150 将PC12细胞和兔髌腱细胞培养4 d后发现纳米纤维上的细胞增殖数量更多
PLLA/
P(LLA-
CL)[27]
导管内填充
纤维
静电
纺丝
PLLA:
598.2±215.1
P(LLA-CL):
899.4±266.3
培养7 d后,SCs已经覆盖了纳米纤维纱线的大部分表面
PLCL/
丝素蛋白[28]
导管内
填充
海绵
静电纺丝+
冷冻干燥
导管主体纤维:
975.51±78.21;
导管内海绵纤维:
987.3±102.01
培养5 d和7 d时,SCs在导管上的细胞活力显著高于中空导管,SCs渗透生长到海绵内部 植入大鼠坐骨神经,第4周和第12周含海绵导管的SFI值、再生的髓鞘神经纤维均大于空心
PLCL[29] 导管
内填充水
凝胶
静电纺丝 DRG培养3 d后神经突在各个方向上都发生生长,最长的突触平行于纳米纤维方向 修复10 mm大鼠坐骨神经,12周后感觉恢复增强

表2

纳米纤维基神经导管的制备方法"

制备方法 适用材料 缺点 优点
静电纺丝 可溶于有机溶剂的高分子材料,如丝素、壳聚糖、PLA、PCL等 强度低、成本高、易造成环境污染 工艺简单可控,可制备功能化纳米纤维
机械分纤 具有多级结构的材料,如丝素 得率低、尺寸不匀率高 纤维强度高、制备方法简单
相分离 结晶聚合物,如壳聚糖、PLLA 纤维直径不可控、尺寸不匀率较高 操作相对简便、无需复杂设备仪器
自组装 分子具有自主装能力的材料,如PLA、丝素、多肽等 制备条件严格、得率低 纤维直径小且可控

图1

静电纺丝法制备的不同结构的纳米纤维"

图2

机械分纤法"

图3

不同结构的神经导管"

图4

静电纺丝纳米纤维纱线填充型的神经导管"

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