Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (7): 3017-3025.doi: 10.4103/NRR.NRR-D-24-01178

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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).

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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