期刊
THERANOSTICS
卷 10, 期 4, 页码 1590-1603出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.36272
关键词
Peripheral nerve injury; electrospinning; mechanical stretching; chitosan nanofibers; peptides
资金
- National Key R&D Program of China [2016YFC1101604]
- Major R&D Program of National Ministry of Science and Technology [2018YFB1105504]
- Chinese National Ministry of Science and Technology 973 Project Planning [2014CB542200]
- National Natural Science Foundation [31771322, 31571235, 81671215, 312 71284, 31171150, 81171146, 30971526, 31100860, 31040043, 31640045, 31671246]
- Beijing Municipal Science and Technology Commission Science and Technology Nova Cross Project [2018019]
- Ministry of Education Innovation Program of China [IRT_16R01, IRT1201]
- R&D foundation of PKUPH [2018-01]
- Educational Ministry New Century Excellent Talents Support Project [BMU20110270]
- National S&T Major Project of China [SQ2018ZX100301]
Autologous nerve transplantation, which is the gold standard for clinical treatment of peripheral nerve injury, still has many limitations. In this study, aligned chitosan fiber hydrogel (ACG) grafted with a bioactive peptide mixture consisting of RGI (Ac-RGIDKRHWNSQGG) and KLT (Ac-KLTWQELYQLKYKGIGG), designated as ACG-RGI/KLT, was used as nerve conduit filler to repair sciatic nerve defects in rats. Methods: Chitosan nanofiber hydrogel was prepared by a combination of electrospinning and mechanical stretching methods, and was then grafted with RGI and KLT, which are peptides mimicking brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), respectively. The physicochemical properties of ACG-RGI/KLT were fully characterized. In vitro, the distribution, proliferation, and secretory activity of Schwann cells were analyzed. Next, the in vivo repair potential for 15-mm rat sciatic nerve defects was examined. The recovery of regenerated nerve, muscle, and motor function was evaluated by neuromuscular histology, electrophysiology, and catwalk gait analysis. Results: We first constructed directionally aligned chitosan nanofiber hydrogel grafted with RGI/KLT peptide mixture (ACG-RGI/KLT). ACG-RGI/KLT oriented the Schwann cells, and promoted the proliferation and secretion of neurotrophic factors by Schwann cells. At an early injury stage, ACG-RGI/KLT not only enhanced nerve regeneration, but also promoted vascular penetration. At 12 weeks, ACG-RGI/KLT facilitated nerve regeneration and functional recovery in rats. Conclusions: Aligned chitosan nanofiber hydrogel grafted with RGI/KLT peptide provides an effective means of repairing sciatic nerve defects and shows great potential for clinical application.
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