In vivo Evaluation of Nanostructured Fibrin-Agarose Hydrogels With Mesenchymal Stem Cells for Peripheral Nerve Repair
In vivo Evaluation of Nanostructured Fibrin-Agarose Hydrogels With Mesenchymal Stem Cells for Peripheral Nerve Repair
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DOI：
10.3389/fncel.2018.00501
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发表时间：
2018-12-18
影响因子：
5.3
通讯作者：
Carriel, Victor
中科院分区：
文献类型：
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作者：
Chato-Astrain, Jesus;Campos, Fernando;Carriel, Victor
周围神经的再生能力非常有限，已经提出了几种策略来增加神经再生。在目前的工作中，我们分析了一种新的纳米结构的纤维蛋白-琼脂糖生物人工神经替代物（纳米）单独使用或与NeuraGen（R）I型胶原导管（Coll-Nano）组合使用在实验室大鼠坐骨神经缺损10 mm的体内有用性。对照动物接受金标准自体移植技术（Auto）。结果首先表明，与Auto组相比，Nano和Coll-Nano组的自我截肢百分比较低。第4周时，Auto组中的神经营养性溃疡（60%，其中66.6%> 2 mm）比Nano和Coll-Nano组（0%）更丰富，尽管Nano在12周后显示出更多的溃疡。12周后，Auto动物的足长因神经性牵拉而发生显著变化，但Nano和Coll-Nano组未发生变化。在功能水平上，所有动物均显示部分感觉恢复，如通过夹捏测试所确定的，尤其是在Nano和Auto组中，但未达到本地动物的水平。足趾伸展试验显示，仅Nano动物在4周时和Auto和Nano动物在12周时部分运动功能恢复。所有实验组的肌电图均显示出明显的去神经迹象，Auto和Nano动物之间几乎没有差异。12周后，Auto和Nano组中发现了重要的去神经减少和神经再支配过程的增加，这些组之间没有差异。组织学分析表明，在所有实验组中，周围神经再生过程活跃，新形成的周围神经束显示S-100、GAP-43和髓鞘。Auto组周围神经再生过程较丰富，Nano组次之，均优于Coll-Nano组。肌肉组织学证实了肌电图结果，并在所有组中显示出一些萎缩和纤维化体征以及重要的重量和体积损失，特别是在Coll-Nano组中（56.8%重量和60.4%体积损失）。所有这些结果表明，在体内使用的新型纳米替代物能够有助于桥接大鼠10 mm周围神经缺损。
The regenerative capability of peripheral nerves is very limited, and several strategies have been proposed to increase nerve regeneration. In the present work, we have analyzed the in vivo usefulness of a novel nanostructured fibrin-agarose bio-artificial nerve substitute (Nano) used alone or in combination with NeuraGen (R) collagen type I conduits (Coll-Nano) in laboratory rats with a 10-mm sciatic nerve defect. Control animals were subjected to the gold-standard autograft technique (Auto). Results first demonstrated that the percentage of self-amputations was lower in Nano and Coll-Nano groups as compared to the Auto group. Neurotrophic ulcers were more abundant in the Auto group (60%, with 66.6% of them being > 2-mm) than Nano and Coll-Nano groups (0%) at 4 weeks, although Nano showed more ulcers after 12 weeks. Foot length was significantly altered in Auto animals due to neurogenic retraction, but not in Nano and Coll-Nano groups after 12 weeks. At the functional level, all animals showed a partial sensory recovery as determined by the pinch test, especially in Nano and Auto groups, but did not reach the levels of native animals. Toe-spread test revealed a partial motor function recovery only in Nano animals at 4 weeks and Auto and Nano at 12 weeks. Electromyography showed clear denervation signs in all experimental groups, with few differences between Auto and Nano animals. After 12 weeks, an important denervation decrease and an increase of the reinnervation process was found in Auto and Nano groups, with no differences between these groups. Histological analyses demonstrated an active peripheral nerve regeneration process with newly formed peripheral nerve fascicles showing S-100, GAP-43 and myelin in all experimental groups. The peripheral nerve regeneration process was more abundant in Auto group, followed by Nano group, and both were better than Coll-Nano group. Muscle histology confirmed the electromyography results and showed some atrophy and fibrosis signs and an important weight and volume loss in all groups, especially in the Coll-Nano group (56.8% weight and 60.4% volume loss). All these results suggest that the novel Nano substitutes used in in vivo were able to contribute to bridge a 10-mm peripheral nerve defect in rats.