中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (11): 2544-2550.doi: 10.4103/1673-5374.339006

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

加载生长因子模拟肽的聚多巴胺涂层甲壳质导管可有效增强周围神经再生

  

  • 出版日期:2022-11-15 发布日期:2022-04-23
  • 基金资助:
    国家自然科学基金项目（31771322，31571235）；北京自然科学基金项目（7212121）；北京科技新星交叉学科（2018019）；深圳市科技计划项目（JCYJ 20190806162205278）；创伤与神经再生教育部重点实验室（北京大学）；国家创伤医学中心项目（BMU2020XY005-01）

Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats

Ci Li1, 2, 3, #, Song-Yang Liu1, 2, 3, #, Li-Ping Zhou4, #, Tian-Tian Min4, Meng Zhang1, 2, 3, Wei Pi1, 2, Yong-Qiang Wen4, *, Pei-Xun Zhang1, 2, 3, *   

  1. 1Department of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, China; 2Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Beijing, China; 3National Center for Trauma Medicine, Beijing, China; 4Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China
  • Online:2022-11-15 Published:2022-04-23
  • Contact: Yong-Qiang Wen, PhD, wyq_wen@ustb.edu.cn; Pei-Xun Zhang, PhD, zhangpeixun@bjmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 31771322, 31571235; the Natural Science Foundation of Beijing, No. 7212121; Beijing Science Technology New Star Cross Subject of China, No. 2018019; Shenzhen Science and Technology Plan Project of China, No. JCYJ 20190806162205278; the Key Laboratory of Trauma and Neural Regeneration (Peking University), Ministry of Education; and a grant from National Center for Trauma Medicine, No. BMU2020XY005-01 (all to PXZ).

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摘要：

将神经营养因子引入损伤部位可促进周围神经再生，但由于神经营养因子在体内的快速降解以及在超生理剂量应用会阻碍轴突再生等问题的存在，其使用受到限制。生物活性肽基于原始生长因子，并简化序列和结构，同时保留其相应受体活化的能力，因而已被用于替代生长因子。实验在覆盖聚多巴胺涂层的甲壳质导管上加载了脑源性神经营养因子模拟肽和血管内皮生长因子模拟肽，并证实了这种导管具有更好的生物相容性，可实现功能肽的持续释放，同时两种功能肽可协同促进许旺细胞的增殖和分泌以及内皮细胞的附着和迁移。而后体内实验以其桥接2mm缺损坐骨神经，结果显示大鼠的后肢运动功能以及神经电传导得到明显改善，可见坐骨神经轴突和髓鞘再生，同时腓肠肌萎缩明显减轻。提示加载生长因子模拟肽的聚多巴胺涂层的甲壳质导管在周围神经修复方面具有巨大的潜力。方案于2020年12月10日经北京大学人民医院动物伦理委员会的批准（批准号2020PHE079）。 

https://orcid.org/0000-0002-9687-8517 (Yong-Qiang Wen); https://orcid.org/0000-0001-7200-2281 (Pei-Xun Zhang)

关键词: 周围神经损伤, 聚多巴胺, 表面改性, 神经营养因子, 生物活性肽, 血管生成, 协同效应, 神经修复, 组织工程, 周围神经再生

Abstract: The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration. However, neurotrophic factors are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose, which limits their clinical benefits. Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth factors and can activate the equivalent receptors but have simplified sequences and structures. In this study, we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth factor mimetic peptides (Chi/PDA-Ps). We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides. In this study, we evaluated the biocompatibility of the Chi/PDA-Ps conduits. Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth factor mimetic peptide synergistically promoted proliferation of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro. The Chi/PDA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury. We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy. The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and remyelination was further restored. These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

Key words: angiogenesis, bioactive peptides, nerve repair, neurotrophic factor, peripheral nerve injury, peripheral nerve regeneration, polydopamine, surface modification, synergistic effects, tissue engineering