中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (16): 2618-2624.doi: 10.12307/2022.267

• 生物材料综述 biomaterial review • 上一篇    

聚乙二醇在神经功能重建领域应用及存在的问题

卫晶晶1，李晨阳2，王  萍1，李雅璇1，丁晓芳1，杨  琳1   

  1. 1遵义医科大学珠海校区，广东省珠海市  519041；2南昌大学，江西省南昌市  330031
  • 收稿日期:2021-03-23 修回日期:2021-03-25 接受日期:2021-05-19 出版日期:2022-06-08 发布日期:2021-12-23
  • 通讯作者: 杨琳，博士，副教授，遵义医科大学珠海校区，广东省珠海市 519041
  • 作者简介:卫晶晶，女，1996年生，山西省运城市人，汉族，遵义医科大学在读硕士，主要从事神经功能重建研究。 李晨阳，男，2001年生，江西省上饶市人，汉族，主要从事化学材料方面的研究。
  • 基金资助:
    国家自然科学基金项目(81760416，81960419，81927804)，项目负责人：杨琳；贵州省普通高等学校科技拔尖人才支持计划(黔教合KY字[2018]056)，项目负责人：杨琳

Application and existing problems of polyethylene glycol in the field of neurological reconstruction

Wei Jingjing1, Li Chenyang2, Wang Ping1, Li Yaxuan1, Ding Xiaofang1, Yang Lin1   

  1. 1Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong Province, China; 2Nanchang University, Nanchang 330031, Jiangxi Province, China
  • Received:2021-03-23 Revised:2021-03-25 Accepted:2021-05-19 Online:2022-06-08 Published:2021-12-23
  • Contact: Yang Lin, PhD, Associate professor, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong Province, China
  • About author:Wei Jingjing, Master candidate, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong Province, China Li Chenyang, Nanchang University, Nanchang 330031, Jiangxi Province, China Wei Jingjing and Li Chenyang contributed equally to this article.
  • Supported by:
    National Natural Science Foundation of China, No. 81760416, 81960419, 81927804 (to YL); Ordinary Colleges and Universities Science and Technology Top Talent Support Program of Guizhou Province, No. Qianjiao He KY [2018] 056 (to YL)

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摘要：

文题释义：
聚乙二醇的细胞融合作用：在聚乙二醇作用下，使相邻的2个或2个以上细胞发生细胞膜融合，细胞膜有内外两层，细胞融合首先发生在外层，然后再到内层，细胞体内物质通过这两种融合通道进行转移，进而合并形成一个细胞，此过程即为聚乙二醇的细胞融合作用。细胞融合可以发生在同种细胞间，也可发生在异种细胞间，其意义具有广泛应用价值。
神经修复：在原有神经解剖和功能基础上，促进被破坏或受损害神经再生修补和重塑、重建神经解剖投射通路和环路、调控和改善神经信号传导、最终实现神经功能修复。

背景：临床上广泛采用自体神经移植来达到神经修复的目的，但应用效果欠佳，而聚乙二醇的应用从细胞融合剂到水凝胶生物黏合剂再到促轴突融合神经修复新型材料等，因此若能联合聚乙二醇探索出加快神经功能重建的方法，可以更好地应用于临床，并且对神经再生与功能重建也具有重要意义。 
目的：阐述聚乙二醇在神经功能重建领域的应用进展。
方法：利用PubMed和中国知网数据库，检索有关聚乙二醇促细胞融合以及聚乙二醇作用于神经修复的文献，检索时间为2020年10月至2021年3月，英文检索词为“PEG，polyethylene glycol，cell-fusion，nerve function reconstruction，nerve repair”，中文检索词为“聚乙二醇、细胞融合、功能重建、神经修复”。根据纳入与排除标准对所有文章进行初筛后，保留相关性较高的61篇文章进行综述。
结果与结论：①在一定条件下，70%聚乙二醇加入少量腺苷5’-三磷酸可加快损伤神经轴突快速生长，有效促进膜的融合，实现神经细胞结构和功能重建。②聚乙二醇自身浓度是促进体细胞融合的主要影响因素，当聚乙二醇浓度为35%，相对分子质量为4 000，或者聚乙二醇浓度为50%，其相对分子质量为1 000时，对细胞融合效率影响最大；其他次要影响因素包括融合细胞个数、反应温度和时间等。③进一步分析聚乙二醇促神经修复的机制发现，聚乙二醇可促进轴突融合，表现出恢复轴突形态的连续性和电生理功能的作用，但是否能在瓦勒氏变性之前实现轴突的有效连接还需进一步研究证明。④聚乙二醇应用前景较为广泛，未来可考虑将其应用在新型生物黏合剂的研发、神经修复支架改良、复合物水凝胶研制相关研究中，但关于聚乙二醇在神经功能重建领域的应用还有诸多问题未解决，如聚乙二醇诱导神经细胞融合对人体的长期影响、最大延迟治疗时间等问题，还需后续研究不断完善。

https://orcid.org/0000-0003-1241-4633 (卫晶晶) ；https://orcid.org/0000-0002-3526-1214 (李晨阳)；https://orcid.org/0000-0003-1372-8677 (杨琳)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 聚乙二醇, 周围神经, 中枢神经, 细胞融合, 轴突融合, 分子机制, 神经修复, 许旺细胞

Abstract: BACKGROUND: Autologous nerve transplantation is widely used clinically to achieve the purpose of nerve repair, but the application effect is not good. The application of polyethylene glycol ranges from cell fusion agents to hydrogel bioadhesives to new materials for promoting axon fusion nerve repair. Therefore, if it can be combined with polyethylene glycol to explore ways to speed up the reconstruction of nerve function, it can be better applied to the clinic, and it will also have important significance for nerve regeneration and functional reconstruction.
OBJECTIVE: To describe the application and progress of polyethylene glycol in the field of neurological reconstruction.
METHODS: PubMed and CNKI were used to retrieve articles about polyethylene glycol promoting cell fusion and polyethylene glycol acting on nerve repair. The search time was from October 2020 to March 2021. The English search terms were “PEG, polyethylene glycol, cell-fusion, nerve function reconstruction, nerve repair”. The Chinese search terms were “polyethylene glycol, cell fusion, function reconstruction, nerve repair”. All articles were initially screened according to the inclusion and exclusion criteria, and 61 articles with higher relevance were retained for review. 
RESULTS AND CONCLUSION: (1) Under certain conditions, 70% polyethylene glycol was added with a small amount of adenosine 5’-triphosphate, which can accelerate the rapid growth of injured nerve axons, effectively promote membrane fusion, and realize the reconstruction of nerve cell structure and function. (2) The main factor affecting the efficiency of cell fusion is the concentration of polyethylene glycol itself. When its concentration is 35%, the relative molecular mass is 4 000, or when the concentration is 50%, the relative molecular mass is 1 000, greatest impact on cell fusion efficiency is found. The other minor influencing factors are the number of fused cells, the reaction temperature, and time. (3) In further research on different mechanisms of promoting nerve repair, polyethylene glycol can promote axon fusion, which is manifested in the restoration of the continuity of axon morphology and its electrophysiological function. However, further research is needed to prove whether the effective connection of axons can be realized before Wallerian degeneration. (4) Polyethylene glycol has a broad application prospect. In the future, it can be considered in the research and development of new bioadhesives, nerve repair stent improvement, and composite hydrogel research. However, the application of polyethylene glycol in the field of nerve function reconstruction still has many unresolved problems, such as the long-term effects of polyethylene glycol-induced neuronal fusion on the human body, and the maximum delay in treatment time, which need to be continuously improved by follow-up research. 

Key words: polyethylene glycol, peripheral nerve, central nerve, cell fusion, axon fusion, molecular mechanism, nerve repair, Schwann cell

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