中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 200-206.doi: 10.4103/1673-5374.343889

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

负载骨髓间充质干细胞来源细胞外囊泡的还原氧化石墨烯包埋神经导管可更好地促进周围神经再生

  

  • 出版日期:2023-01-15 发布日期:2022-06-17
  • 基金资助:

    国家自然科学基金项目(31671248),北京市自然科学基金项目(7222198

Reduced graphene oxide-embedded nerve conduits loaded with bone marrow mesenchymal stem cell-derived extracellular vesicles promote peripheral nerve regeneration

Wei Zhang1, 2, Xing-Xing Fang1, 2, Qi-Cheng Li1, 2, Wei Pi1, 2, Na Han1, 2, 3, *   

  1. 1Department of Orthopedics and Trauma, Peking University People’s Hospital, Beijing, China; 2National Center for Trauma Medicine, Beijing, China; 3Central Laboratory, Peking University People’s Hospital, Beijing, China
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Na Han, PhD, hannaqa@hotmail.com.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 31671248 and the Natural Science Foundation of Beijing, No. 7222198 (both to NH).

摘要:

虽然以还原氧化石墨烯与明胶-甲基丙烯酰和聚己内酯结合制成的还原氧化石墨烯-甲基丙烯酸化水凝胶-聚己内酯神经导管的导电性和生物相容性有所改善,但是其对损伤周围神经再生和轴突延伸的作用仍与自体神经移植有较大的差距。由于骨髓间充质干细胞来源细胞外囊泡具有促进损伤部位血管再生的作用,因此可将其负载于这种神经导管中,用于修复大鼠坐骨神经缺损。结果显示这种负载骨髓间充质干细胞来源细胞外囊泡的还原氧化石墨烯包埋神经导管修复的大鼠损伤部位导管内新生血管数量以及神经功能的恢复和轴突的再生情况,均优于不负载细胞外囊泡的导管修复的大鼠。这些发现为负载骨髓间充质干细胞来源细胞外囊泡的还原氧化石墨烯-甲基丙烯酸化水凝胶-聚己内酯神经导管促进周围神经再生和功能恢复提供了证据。

https://orcid.org/0000-0002-5099-714X (Wei Zhang)

关键词: 周围神经损伤, 骨髓间充质干细胞, 细胞外囊泡, 混合纳米纤维, 血管生成, 还原氧化石墨烯, 轴突, 髓鞘, 神经功能, 神经导管

Abstract: We previously combined reduced graphene oxide (rGO) with gelatin-methacryloyl (GelMA) and polycaprolactone (PCL) to create an rGO-GelMA-PCL nerve conduit and found that the conductivity and biocompatibility were improved. However, the rGO-GelMA-PCL nerve conduits differed greatly from autologous nerve transplants in their ability to promote the regeneration of injured peripheral nerves and axonal sprouting. Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSCs) can be loaded into rGO-GelMA-PCL nerve conduits for repair of rat sciatic nerve injury because they can promote angiogenesis at the injured site. In this study, 12 weeks after surgery, sciatic nerve function was measured by electrophysiology and sciatic nerve function index, and myelin sheath and axon regeneration were observed by electron microscopy, immunohistochemistry, and immunofluorescence. The regeneration of microvessel was observed by immunofluorescence. Our results showed that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles were superior to rGO-GelMA-PCL conduits alone in their ability to increase the number of newly formed vessels and axonal sprouts at the injury site as well as the recovery of neurological function. These findings indicate that rGO-GelMA-PCL nerve conduits loaded with BMSC-derived extracellular vesicles can promote peripheral nerve regeneration and neurological function recovery, and provide a new direction for the curation of peripheral nerve defect in the clinic.

Key words: angiogenesis, axon, bone mesenchymal stem cell, extracellular vesicles, hybrid nanofibers, myelin sheath, nerve conduit, neurological function, peripheral nerve injury, reduced graphene oxide