中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (3): 664-670.doi: 10.4103/1673-5374.350213

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

脱细胞神经基质支架抑横断周围损伤神经残端中神经瘤的形成

  

  • 出版日期:2023-03-15 发布日期:2022-08-28
  • 基金资助:

    中国国家自然科学基金项目(82171650);广东省重点研发项目(2020B1111150003);广东省基础与应用基础研究基金项目(2020A1515011143

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury

Shuai Qiu1, #, Pei-Jun Deng1, #, Fu-Lin He2, Li-Wei Yan1, Zhe-Hui Tu3, Xiao-Lin Liu1, 4, 5, Da-Ping Quan4, 6, 7, Ying Bai4, 5, 7, Can-Bin Zheng1, 4, 5, *, Qing-Tang Zhu1, 4, 5, *   

  1. 1Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 2Department of Orthopedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China; 3Department of Pediatric Orthopedics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China; 4Guangdong Provincial Peripheral Nerve Tissue Engineering and Technology Research Center, Guangzhou, Guangdong Province, China; 5Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China; 6School of Chemistry, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 7School of Material Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong Province, China *Correspondence to: Qing-Tang Zhu, MD, PhD, zhuqingt@mail.sysu.edu.cn; Can-Bin Zheng, MD, PhD, zhengcb3@mail.sysu.edu.cn.
  • Online:2023-03-15 Published:2022-08-28
  • Contact: Qing-Tang Zhu, MD, PhD, zhuqingt@mail.sysu.edu.cn; Can-Bin Zheng, MD, PhD, zhengcb3@mail.sysu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 82171650 (to CBZ); Guangdong Province Key Research and Development Project, No. 2020B1111150003 (to DPQ); and Guangdong Basic and Applied Basic Research Foundation, No. 2020A1515011143 (to CBZ)

摘要:

创伤性痛性神经瘤是损伤部位周围细胞外基质异常沉积的表现。研究表明,天然神经的微观结构是适宜神经末梢避免神经异常增生和神经瘤形成的微环境。此次实验旨在通过脱细胞神经基质支架预防大鼠坐骨神经横断后痛性神经瘤的形成。(1)结果可见脱细胞神经基质支架可有效地减少细胞外基质的异常沉淀,引导轴突有序再生排布,并降低再生轴突密度,而其神经束膜-神经外膜屏障阻止了血管肌肉瘢痕组织的侵袭,显著地减少了α平滑肌肌动蛋白阳性肌成纤维细胞侵入神经残端,有效抑制其瘢痕化,从而诱导神经残端逐渐重塑再生接近于正常神经的组织形态,缓解动物的疼痛自噬行为。(2)这些结果表明通过细胞外基质重塑优化脱细胞神经基质支架的神经瘤微环境的重建可能是预防创伤性痛性神经瘤神经病变的一种潜在策略。

https://orcid.org/0000-0001-6256-1602 (Qing-Tang Zhu); https://orcid.org/0000-0002-4560-8242 (Can-Bin Zheng); https://orcid.org/0000-0001-7594-7619 (Shuai Qiu)

关键词: 创伤性神经瘤, 细胞外基质, 微环境, 微架构, 疼痛, 脱细胞神经基质支架, 纤维化, 周围神经, 组织重塑, 功能恢复

Abstract: Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas. 

Key words: decellularized nerve matrix scaffold, extracellular matrix, fibrosis, functional recovery, microarchitecture, microenvironment, pain, peripheral nerve, tissue remodeling, traumatic neuroma