中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (1): 105-111.doi: 10.4103/1673-5374.224377

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

促进背根神经节细胞迁移和伸展的微图案化聚乳酸-羟基乙酸共聚物膜的优化

  

  • 收稿日期:2017-11-14 出版日期:2018-01-15 发布日期:2018-01-15

Optimization of micropatterned poly(lactic-coglycolic acid) films for enhancing dorsal root ganglion cell orientation and extension

Ching-Wen Li1, Brett Davis2, Jill Shea2, Himanshu Sant3, Bruce Kent Gale3, Jayant Agarwal2   

  1. 1 Department of Mechanical Engineering, National Chung Hsing University, Taichung, Taiwan, China
    2 Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT, USA
    3 Department of Mechanical Engineering, University of Utah, Salt Lake City, UT, USA
  • Received:2017-11-14 Online:2018-01-15 Published:2018-01-15
  • Contact: Jayant Agarwal, M.D.,jay.agarwal@hsc.utah.edu.

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摘要：

神经导管已经成为可替代“金标准”自体移植物用于周围神经缺损的修复手段。然而，其也存在修复后功能恢复不理想和不适用于大段神经缺损的缺陷。已有研究显示脊/凹槽表面微图案可促进神经细胞生长取向，并引导其生长。然而，目前尚未见可促进微图案化聚乳酸-羟基乙酸共聚物膜上背根神经节细胞生长取向和伸展的脊/凹槽最佳比例参数的研究。实验使用光刻法和微热模塑法得到聚乳酸-羟基乙酸共聚物膜上的脊/凹槽尺寸的各种组合。将来源于鸡胚的背根神经节细胞在微图案化聚乳酸-羟基乙酸共聚物膜上培养后，进行细胞定向和迁移评估。在测试期间发生的膜生物降解不会导致微图案变形或扭曲。背根神经节细胞取向测试结果显示，当脊/凹槽比率等于1时，细胞排列整齐度取决于脊和凹槽的尺寸；当这一比率小于1时，随着脊的尺寸减小，排列整齐度增加；当这一比率大于1时，随着凹槽的宽度减小，排列整齐度减小。在10 μm/10 μm和30 μm/30 μm的微图案化聚乳酸-羟基乙酸共聚物膜上培养的背根神经节神经元的迁移率和轴突延伸率最高，由此认为10 μm/10 μm和30 μm/30 μm是促进背根神经节细胞迁移和伸展的最佳脊/凹槽表面尺寸组合。

orcid:0000-0002-1209-6703(Jayant Agarwal)

关键词: 神经再生, 神经修复, 神经细胞迁移, 神经细胞排列, 微图案, 背根神经节, 拓扑

Abstract:

Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion (DRG) cells on poly(lactic-co-glycolic acid) (PLGA) films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation.Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 (ridge/groove width parameters are equal, i.e., 10 μm/10 μm (even)), the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 (groove controlled) the alignment increases as the ridge size decreases, and when the ratio is larger than 1 (ridge controlled), the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.

Key words: nerve regeneration, nerve repair, neural cell migration, neural cell alignment, micropattern, dorsal root ganglion, topological cues, neural regeneration