Rochkind Shimon, Almog Mara, Meilin Sigal, Nevo Zvi
Research Center for Nerve Reconstruction, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Neurology R&D Division, MD Biosciences, Ness Ziona, Israel.
Front Surg. 2021 Jan 15;7:609638. doi: 10.3389/fsurg.2020.609638. eCollection 2020.
The aim of this study was to investigate the innovative guiding regenerative gel (GRG) and antigliotic GRG (AGRG) fillings for nerve conduits, prepared with Food and Drug Administration (FDA)-approved agents and expected to provide an alternative to autologous nerve graft and to enable reconnection of massive nerve gaps in a rabbit model of chronic peripheral nerve injury with massive loss defect that simulates the human condition of chronic injury with a large gap. The components and dosimetry for GRG and AGRG formulations were investigated on nerve cell culture and on 10-mm reconstructed sciatic nerves of 72 rats using different concentrations of agents and completed on a rabbit model of delayed (chronic) complete peripheral nerve injury with a 25-mm gap. Forty rabbits underwent delayed (9 weeks after complete injury of the tibial portion of the sciatic nerve) nerve tube reconstruction of a gap that is 25 mm long. GRG and AGRG groups were compared with autologous and empty tube reconstructed groups. Rats and rabbits underwent electrophysiological and histochemical assessments (19 weeks for rats and 40 weeks for rabbits). Application of AGRG showed a significant increase of about 78% in neurite length per cell and was shown to have the most promising effect on neuronal outgrowth, with total number of neurites increasing by 4-fold. The electrophysiological follow-up showed that AGRG treatment is most promising for the reconstruction of the tibial portion of the sciatic nerve with a critical gap of 25 mm. The beneficial effect of AGRG was found when compared with the autologous nerve graft reconstruction. Thirty-one weeks post the second surgery (delayed reconstruction), histochemical observation showed significant regeneration after using AGRG neurogel, compared with the empty tube, and succeeded in significantly regenerating the nerve, as well as the autologous nerve graft, which was almost similar to a healthy nerve. We demonstrate that in the model of delayed peripheral nerve repair with massive loss defect, the application of AGRG led to a stronger nerve recovery and can be an alternative to autologous nerve graft.
本研究的目的是研究创新的引导再生凝胶（GRG）和抗神经胶质GRG（AGRG）填充物用于神经导管，这些填充物由美国食品药品监督管理局（FDA）批准的试剂制备，有望替代自体神经移植，并能在模拟人类慢性损伤且伴有大间隙的慢性周围神经损伤兔模型中实现大面积神经间隙的重新连接。在神经细胞培养以及使用不同浓度试剂的72只大鼠的10毫米重建坐骨神经上研究了GRG和AGRG配方的成分和剂量，并在有25毫米间隙的延迟（慢性）完全性周围神经损伤兔模型上完成。40只兔子在坐骨神经胫部完全损伤9周后接受了25毫米长间隙的延迟神经管重建。将GRG和AGRG组与自体和空管重建组进行比较。对大鼠和兔子进行电生理和组织化学评估（大鼠为19周，兔子为40周）。AGRG的应用显示每个细胞的神经突长度显著增加约78%，并且对神经元生长显示出最有前景的效果，神经突总数增加了4倍。电生理随访表明，AGRG治疗对于重建有25毫米关键间隙的坐骨神经胫部最有前景。与自体神经移植重建相比，发现了AGRG的有益效果。第二次手术（延迟重建）后31周，组织化学观察显示，与空管相比，使用AGRG神经凝胶后有显著再生，并且成功地使神经以及自体神经移植显著再生，几乎与健康神经相似。我们证明，在伴有大面积损失缺陷的延迟性周围神经修复模型中，AGRG的应用导致更强的神经恢复，并且可以替代自体神经移植。
