Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting. In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study. We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.

中文翻译：

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血管内皮生长因子和神经生长因子基因的双重递送增强坐骨神经再生

周围神经损伤是世界范围内的一种常见临床疾病，鉴于坐骨神经的长度和较大的横截面积，其在解剖学上是再生方面最具挑战性的疾病。目前，当治疗坐骨神经损伤时，自体神经移植仍然是最理想的策略。但是，这种方法牺牲了健康的神经，需要进行高强度的手术，仍然需要其他先进的神经移植方法。在这项研究中，我们利用以前建立良好的基因传递系统，双重传递编码血管内皮生长因子（VEGF）和神经生长因子（NGF）的质粒DNA（pDNA），探索坐骨神经损伤的治疗方法。低分子量支链聚乙烯亚胺（bPEI）被构建为基因载体的主链结构，并通过二醛的偶联进一步交联以合成可降解的聚阳离子。在这项研究中观察到VEGF和NGF蛋白之间的协同作用对大鼠坐骨神经挤压伤模型。我们得出结论，质粒VEGF和NGF的双重递送作为基因治疗可以增强坐骨神经再生。