Yurie Hirofumi, Ikeguchi Ryosuke, Aoyama Tomoki, Kaizawa Yukitoshi, Tajino Junichi, Ito Akira, Ohta Souichi, Oda Hiroki, Takeuchi Hisataka, Akieda Shizuka, Tsuji Manami, Nakayama Koichi, Matsuda Shuichi
Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Physical Therapy, Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
PLoS One. 2017 Feb 13;12(2):e0171448. doi: 10.1371/journal.pone.0171448. eCollection 2017.
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.
尽管自体神经移植是周围神经损伤的金标准治疗方法,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,注入神经移植物中的支持细胞的接种效率和活力仍不清楚。在此,我们专注于一种新型的完全生物的、组织工程的、无支架导管。
我们使用生物3D打印机从人正常真皮成纤维细胞开发了六种无支架导管。十二只成年雄性免疫缺陷大鼠接受右坐骨神经大腿中段横断术。使用8毫米生物3D导管(生物3D组,n = 6)和硅胶管(硅胶组,n = 6)桥接产生的5毫米神经间隙。在手术后八周进行了几项评估以检查神经再生情况。
运动学分析显示,生物3D组摆动期最后阶段脚趾与跖骨的角度明显高于硅胶组(分别为-35.78±10.68与-62.48±6.15;p<0.01)。电生理研究显示,生物3D组的复合肌肉动作电位明显高于硅胶组(53.60±26.36%对2.93±1.84%;p<0.01)。组织学和形态学研究显示再生神经的所有区域都有神经细胞表达,并且生物3D组中有许多髓鞘良好的轴突。生物3D组胫前肌的湿肌肉重量明显高于硅胶组(分别为0.544±0.063对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生物3D导管在大鼠坐骨神经模型中促进神经再生。