Aligned Chitosan Nanofiber Hydrogel Grafted with RGI/KLT Peptide Repair Sciatic Nerve Defect

Background: Autologous nerve transplantation as the gold standard of clinical treatment of peripheral nerve injury still has many limitations. In this study, aligned chitosan nanofibers hydrogel grafted with RGI/KLT peptide was used as nerve conduit filler to repair sciatic nerve defects in rats, and its effectiveness was evaluated.   Methods: Chitosan nanofibers hydrogel was prepared by a combination of electrospinning and mechanical stretching, then grafted with RGI and KLT, which are BDNF and VEGF mimicking peptides respectively. The physicochemical properties of chitosan nanofibers hydrogel grafted with RGI/KLT peptide were detected. The distribution, proliferation and secretion of Schwann cells were detected. A 15 mm sciatic nerve defect model was established in rats. The recovery of regenerated nerve, muscle and motor function was evaluated by neuromuscular histology, electrophysiology and catwalk gait analysis.   Results: Aligned chitosan nanofibers hydrogel grafted with RGI/KLT peptide could orientate the distribution of SCs, promote the proliferation of SCs and secretion of neurotrophic factors. At 12 weeks after operation, aligned chitosan nanofibers hydrogel grafted with RGI/KLT peptide can promote nerve regeneration and functional recovery in rats. Early after operation, ACG-RGI/KLT can not only promote nerve regeneration, but also promote vascular regeneration, thereby improving local microcirculation.   Conclusions: Aligned chitosan nanofibers hydrogel grafted with RGI/KLT peptide is effective in repairing sciatic nerve defect and has a very good clinical application prospect.   Funding Statement: This work is supported by 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 (No. 2014CB542200), National Natural Science Foundation (31771322, 31571235, 81671215, 31271284, 31171150, 81171146, 30971526, 31100860, 31040043, 31640045, 31671246), Beijing Municipal Science and Technology Commission Science and Technology Nova Cross Project (2018019), the Ministry of Education Innovation Program of China, (IRT_16R01, IRT1201), the R&D foundation of PKUPH (2018-01), the Educational Ministry New Century Excellent Talents Support Project (No. BMU20110270), National S&T Major Project of China (SQ2018ZX100301). Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: The study followed the Laboratory animal Guideline for ethical review of animal welfare of China (GB/T 35892-2018). All experiments were complied with the relevant regulations of Medical Ethics Committee of Peking University People’s Hospital.