Aligned chitosan nanofiber hydrogel grafted with peptides mimicking bioactive brain-derived neurotrophic factor and vascular endothelial growth factor repair long-distance sciatic nerve defects in rats
Aligned chitosan nanofiber hydrogel grafted with peptides mimicking bioactive brain-derived neurotrophic factor and vascular endothelial growth factor repair long-distance sciatic nerve defects in rats
复制标题
对齐的壳聚糖纳米纤维水凝胶接枝模拟生物活性脑源性神经营养因子和血管内皮生长因子的肽修复大鼠长距离坐骨神经缺损
DOI：
10.7150/thno.36272
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Jiang, Baoguo
中科院分区：
文献类型：
--
作者：
Rao, Feng;Wang, Yanhua;Jiang, Baoguo
自体神经移植是临床治疗周围神经损伤的金标准，但仍有许多局限性。本研究将由RGI（Ac-RGIDKRHWNSQGG）和KLT（Ac-KLTWQELYQLKYKGIGG）组成的生物活性肽混合物（ACG-RGI/KLT）接枝到定向壳聚糖纤维水凝胶（ACG）上，作为神经导管填充物修复大鼠坐骨神经缺损。研究方法：采用静电纺丝和机械拉伸相结合的方法制备壳聚糖凝胶，并分别与脑源性神经营养因子（BDNF）和血管内皮生长因子（VEGF）模拟肽RGI和KLT接枝。对ACG-RGI/KLT的理化性质进行了全面表征。在体外，雪旺细胞的分布，增殖和分泌活性进行了分析。接下来，检查15-mm大鼠坐骨神经缺损的体内修复潜力。通过神经肌肉组织学、电生理学和猫步步态分析评价再生神经、肌肉和运动功能的恢复。结果：我们首先构建了接枝RGI/KLT肽混合物的定向排列壳聚糖纳米纤维水凝胶（ACG-RGI/KLT）。ACG-RGI/KLT对许旺细胞有定向作用，促进许旺细胞增殖和分泌神经营养因子。在损伤早期，ACG-RGI/KLT不仅促进神经再生，而且促进血管穿透。12周时，ACG-RGI/KLT促进大鼠神经再生和功能恢复。结论：RGI/KLT肽接枝的定向壳聚糖水凝胶为坐骨神经缺损的修复提供了一种有效的手段，具有很大的临床应用潜力。
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.