中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3017-3025.doi: 10.4103/NRR.NRR-D-24-01178

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

缺氧缺血性脑病的创新疗法：以丝素蛋白纳米材料促进神经干细胞轴突发育进而促进认知改善

  

  • 出版日期:2026-07-15 发布日期:2026-03-27
  • 基金资助:
    大连市科技人才创新支持政策实施计划高层次人才团队项目(编号2022RG18)、辽宁省科技计划定向项目(编号[2021]49)、大连市支持高层次人才创新创业项目(编号2021RQ028)、辽宁省自然科学基金计划项目(编号2022-BS-238)

An innovative treatment for hypoxic–ischemic encephalopathy: Silk fibroin nanomaterials improve neural stem cell axon formation and facilitate cognitive improvement

Chao Han1, 2, 3, #, Shuna Chen1, 2, 4, #, Zihan Shi2, 3, Xin Guan1, 2, Wei Zou2, Jing Liu1, 2, *   

  1. 1Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China; 
    2Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China; 
    3College of Integrated Chinese and Western Medicine, Dalian Medical University, Dalian, Liaoning Province, China;  4Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
  • Online:2026-07-15 Published:2026-03-27
  • Contact: Jing Liu, PhD, liujing@dmu.edu.cn.
  • Supported by:
    This study was supported by the Dalian Science and Technology Talent Innovation Support Policy Implementation Plan High-Level Talent Team, No. 2022RG18 (to JL); the Science and Technology Plan Orientation of Liaoning Province, No. [2021]49 (to JL); Dalian High-Level Talent Innovation Support Plan, No. 2021RQ028 (to CH); and the Natural Science Foundation of Liaoning Province, No. 2022-BS-238 (to CH).

PDF

0

摘要：

干细胞疗法具有治疗脑损伤的前景，其中神经干细胞能够通过形成新的神经细胞来修复损伤并支持神经功能的恢复。然而，优化神经干细胞植入受损脑区以及增强细胞功能仍然具有挑战性。丝素蛋白是一种从蚕丝中提取的天然蛋白质，具有良好的生物相容性和卓越的组织工程性能。丝素蛋白的生物降解性、机械稳定性和促进细胞生长的能力使其在生物医学领域具有广泛的前景。丝素蛋白纳米材料是一种将丝素蛋白加工成纳米结构的特殊材料，其与块状丝素蛋白材料相比，具有更大的表面积、更高的生物活性分子负载能力以及更强的细胞相互作用。此次实验首先从14周龄胚胎中提取人源性神经干细胞。然后以丝素蛋白纳米材料负载神经干细胞，确定1%丝素蛋白纳米材料是支持人源性神经干细胞生长和神经营养因子释放的最佳浓度。最后对缺氧缺血性脑损伤大鼠模型植入1%丝素蛋白纳米材料，结果显示，与单独使用人源性神经干细胞治疗相比，丝素蛋白水凝胶搭载人源性神经干细胞在缓解脑组织损伤、改善脑内微环境中神经营养因子分泌、促进运动和认知功能恢复方面效果更为显著。这些研究表明，这种丝素蛋白纳米材料可通过促进人源性神经干细胞的神经元分化，并支持神经营养因子分泌，从而促进缺氧缺血性脑损伤后神经功能的恢复。提示丝素蛋白纳米材料搭载人源性神经干细胞可成为治疗缺氧缺血性脑病的潜在策略。


https://orcid.org/0000-0002-0493-296X (Jing Liu)

关键词: 神经干细胞, 缺氧缺血性脑损伤, 丝素蛋白水凝胶, 神经再生, 轴突发育, 突触形成, 神经营养因子, 星形胶质细胞失活, 运动功能, 认知恢复

Abstract: Stem cell therapy shows promise for treating brain injuries; neural stem cells in particular are capable of repairing damage by forming new nerve cells and supporting recovery. However, optimizing the implantation and functionality of these cells in damaged brain regions remains challenging. Silk fibroin, a natural protein derived from silkworm silk, is a biocompatible material with exceptional properties that are useful for tissue engineering. Its biodegradability, mechanical robustness, and ability to promote cell growth make it particularly valuable for biomedical applications. Silk fibroin nanomaterials, which comprise silk fibroin processed into nanostructures, offer enhanced surface area, improved loading capacity for bioactive molecules, and superior nanoscale interactions with cells compared with bulk silk fibroin materials. In this study, we first extracted human-derived neural stem cells from a 14-week-old human fetus. Then, neural stem cells were loaded with 1% silk fibroin nanomaterials, which was identified as the optimal concentration to support human-derived neural stem cell growth and release of neurotrophic factors. Finally, 1% silk fibroin nanomaterials were implanted into a rat model of hypoxic-ischemic brain injury. The results showed that, compared with the treatment with human-derived neural stem cells alone, silk fibroin hydrogel carrying human-derived neural stem cells was significantly more effective at alleviating brain tissue damage, increasing neurotrophic factor secretion in the brain microenvironment, and promoting motor and cognitive function recovery. These findings suggest that silk fibroin nanomaterials loaded with human-derived neural stem cells could be used to treat hypoxic-ischemic ncephalopathy. However, the mechanisms and related signaling pathways by which hydrogels combined with cells exert their reparative effects still require further in-depth investigation.

Key words: astrocyte deactivation, axonal development, cognitive recovery, hypoxic–ischemic brain injury, motor function, nerve regeneration, neural stem cells, neurotrophic factor, silk fibroin hydrogel, synapse formation