Bilayer nerve guidance conduits for continuous delivery of NGF@ZIF-8 nanoparticles for peripheral nerve injury repair

  • J Nanobiotechnology. 2026 May 25. doi: 10.1186/s12951-026-04553-5.
Xu Zhang  #  1  2 ,  Qian Zhu  #  1 ,  Hao Rong  #  3 ,  Siyao Zhu  #  4 ,  Pan Feng  1 ,  Jing Li  1 ,  Yusong Wang  1 ,  Hong Cheng  1 ,  Wenbo Liu  5  6 ,  Jie Sun  7  8 ,  Zhisen Shen  9 ,  Jilai Li  10 ,  Yangnan Hu  11  12 ,  Renjie Chai  13  14  15  16  17  18
Affiliations
  • 1. State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Zhongda Hospital, Southeast University, Nanjing, 210096, China.
  • 2. Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China.
  • 3. The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315000, China.
  • 4. Harvard T. H. Chan School of Public Health, 158 Longwood Avenue, Boston, 02115, MA, US.
  • 5. Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
  • 6. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Nanjing, Jiangsu, China.
  • 7. Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China. [email protected].
  • 8. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Nanjing, Jiangsu, China. [email protected].
  • 9. The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315000, China. [email protected].
  • 10. Department of Neurology, Aerospace Center Hospital, Peking University Aerospace Clinical College, Beijing, 100049, China. [email protected].
  • 11. State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Zhongda Hospital, Southeast University, Nanjing, 210096, China. [email protected].
  • 12. School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai, 519088, China. [email protected].
  • 13. State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Zhongda Hospital, Southeast University, Nanjing, 210096, China. [email protected].
  • 14. Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China. [email protected].
  • 15. School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai, 519088, China. [email protected].
  • 16. Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing, 100081, China. [email protected].
  • 17. Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China. [email protected].
  • 18. Southeast University Shenzhen Research Institute, Shenzhen, 518063, China. [email protected].
  • # Contributed equally.
PMID: 42185827 DOI: 10.1186/s12951-026-04553-5
Abstract

Peripheral nerve injury remains a major clinical challenge due to limited regenerative capacity and insufficient therapeutic strategies. In this study, we developed biomimetic nerve guidance conduits composed of high-concentration gelatin methacryloyl (GelMA) hydrogel (GMH), providing mechanical support and structural integrity. The conduits lumen was filled with a softer, low-concentration GelMA hydrogel (GML) incorporating zeolitic imidazolate framework-8 (ZIF-8) nanoparticles encapsulating nerve growth factor (NGF), enabling sustained neurotrophic delivery. This bilayer design combines mechanical reinforcement with localized biochemical stimulation. In vitro experiments demonstrate that the system can continuously release NGF, exhibits good cellular compatibility, promotes neurite outgrowth in PC-12 cells, and can facilitate the conversion of RAW264.7 cells to an anti-inflammatory phenotype. Rat sciatic nerve injury model experiments have demonstrated that these nerve guidance conduits have a beneficial effect on the regeneration and functional recovery of nerve axons. Together, these findings highlight a versatile platform for nerve guidance conduits with the potential to improve functional recovery in peripheral nerve regeneration.

Keywords
Bilayer nerve guidance conduits; GelMA hydrogel; Nerve growth factor; Peripheral nerve regeneration; ZIF-8.
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