The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model.
The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model.
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DOI：
10.1371/journal.pone.0171448
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Matsuda S
中科院分区：
文献类型：
--
作者：
Yurie H;Ikeguchi R;Aoyama T;Kaizawa Y;Tajino J;Ito A;Ohta S;Oda H;Takeuchi H;Akieda S;Tsuji M;Nakayama K;Matsuda S
虽然自体神经移植是治疗周围神经损伤的金标准，但已经开发了几种替代方法，包括使用支持细胞的神经导管。然而，在神经移植物中注射的支持细胞的接种效率和存活率仍然不清楚。在这里，我们专注于一种新的完全生物的，组织工程的，无支架的管道。我们使用Bio 3D打印机从人类正常皮肤成纤维细胞开发了六个无支架导管。12只免疫缺陷的成年雄性大鼠接受了右侧坐骨神经的大腿中段水平横断。使用8 mm Bio 3D导管（Bio 3D组，n = 6）和硅胶管（硅胶组，n = 6）桥接产生的5 mm神经间隙。进行了几项评估，以检查手术后8周的神经再生。运动学分析显示，Bio 3D组在摆动阶段的最后一段脚趾与跖骨的角度显著高于硅胶组（分别为-35.78 ± 10.68 vs-62.48 ± 6.15; p < 0.01）。电生理学研究显示，Bio 3D组的复合肌肉动作电位显著高于硅胶组（53.60 ± 26.36% vs 2.93 ± 1.84%; p < 0.01）。组织学和形态学研究显示，在Bio 3D组中，再生神经的所有区域都有神经细胞表达，并且存在许多有髓鞘的轴突。Bio 3D组胫骨前肌的湿肌重量显著高于硅胶组（分别为0.544 ± 0.063和0.396 ± 0.031; p < 0.01）。我们证实，完全由成纤维细胞组成的无支架Bio 3D导管在大鼠坐骨神经模型中促进神经再生。
Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.