Yu Hailong, Peng Jiang, Guo Quanyi, Zhang Li, Li Zhi, Zhao Bin, Sui Xiang, Wang Yu, Xu Wenjing, Lu Shibi
Key Laboratory of People's Liberation Army, Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China.
Microsurgery. 2009;29(4):330-6. doi: 10.1002/micr.20635.
Previous studies have demonstrated the potential of growth factors in peripheral nerve regeneration. A method was developed for sustained delivery of nerve growth factor (NGF) for nerve repair with acellular nerve grafts to augment peripheral nerve regeneration. NGF-containing polymeric microspheres were fixed with fibrin glue around chemically extracted acellular nerve grafts for prolonged, site-specific delivery of NGF. A total of 52 Wistar rats were randomly divided into four groups for treatment: autografting, NGF-treated acellular grafting, acellular grafting alone, and acellular grafting with fibrin glue. The model of a 10-mm sciatic nerve with a 10-mm gap was used to assess nerve regeneration. At the 2nd week after nerve repair, the length of axonal regeneration was longer with NGF-treated acellular grafting than acellular grafting alone and acellular grafting with fibrin glue, but shorter than autografting (P < 0.05). Sixteen weeks after nerve repair, nerve regeneration was assessed functionally and histomorphometrically. The percentage tension of the triceps surae muscles in the autograft group was 85.33 +/- 5.59%, significantly higher than that of NGF-treated group, acellular graft group and fibrin-glue group, at 69.79 +/- 5.31%, 64.46 +/- 8.48%, and 63.35 +/- 6.40%, respectively (P < 0.05). The ratio of conserved muscle-mass was greater in the NGF-treated group (53.73 +/- 4.56%) than in the acellular graft (46.37 +/- 5.68%) and fibrin glue groups (45.78 +/- 7.14%) but lower than in the autograft group (62.54 +/- 8.25%) (P < 0.05). Image analysis on histological observation revealed axonal diameter, axon number, and myelin thickness better with NGF-treated acellular grafting than with acellular grafting alone and acellular grafting with fibrin glue (P < 0.05). There were no significant differences between NGF-treated acellular grafting and autografting. This method of sustained site-specific delivery of NGF can enhance peripheral nerve regeneration across short nerve gaps repaired with acellular nerve grafts.
以往研究已证明生长因子在周围神经再生中的潜力。本研究开发了一种利用脱细胞神经移植物持续递送神经生长因子（NGF）以促进周围神经再生的神经修复方法。含NGF的聚合物微球用纤维蛋白胶固定在化学提取的脱细胞神经移植物周围，以实现NGF的长期、位点特异性递送。总共52只Wistar大鼠被随机分为四组进行治疗：自体移植组、NGF处理的脱细胞移植组、单纯脱细胞移植组和纤维蛋白胶脱细胞移植组。采用10毫米坐骨神经缺损10毫米的模型评估神经再生情况。神经修复后第2周，NGF处理的脱细胞移植组轴突再生长度长于单纯脱细胞移植组和纤维蛋白胶脱细胞移植组，但短于自体移植组（P<0.05）。神经修复后16周，对神经再生进行功能和组织形态计量学评估。自体移植组腓肠肌的张力百分比为85.33±5.59%，显著高于NGF处理组、脱细胞移植组和纤维蛋白胶组，后三组分别为69.79±5.31%、64.46±8.48%和63.35±6.40%（P<0.05）。NGF处理组的保留肌肉质量比高于脱细胞移植组（46.37±5.68%）和纤维蛋白胶组（45.78±7.14%），但低于自体移植组（62.54±8.25%）（P<0.05）。组织学观察的图像分析显示，NGF处理的脱细胞移植组的轴突直径、轴突数量和髓鞘厚度优于单纯脱细胞移植组和纤维蛋白胶脱细胞移植组（P<0.05）。NGF处理的脱细胞移植组与自体移植组之间无显著差异。这种NGF的持续位点特异性递送方法可增强脱细胞神经移植物修复短神经缺损后的周围神经再生。
