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静电纺丝丝-聚苯胺导管在大鼠坐骨神经损伤模型中的功能神经再生作用。

Electrospun silk-polyaniline conduits for functional nerve regeneration in rat sciatic nerve injury model.

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati-781039, Assam, India.

出版信息

Biomed Mater. 2017 Aug 17;12(4):045025. doi: 10.1088/1748-605X/aa7802.

Abstract

The present study describes the fabrication of polyaniline-silk fibroin (PASF) nanocomposite-based nerve conduits and their subsequent implantation in a rat sciatic nerve injury model for peripheral nerve regeneration. This is the first in vivo study of polyaniline-based nerve conduits describing the safety and efficacy of the conduits in treating peripheral nerve injuries. The nanocomposite was synthesized by electrospinning a mixture of silk fibroin protein and polyaniline wherein the silk nanofibers were observed to be uniformly coated with polyaniline nanoparticles. Tubular shaped nerve conduits were subsequently formed by multiple rolling of the electrospun sheet over a stainless steel mandrel. The conduits were characterized in vitro for their physico-chemical properties as well as their compatibility with rat Schwann cells. Upon implantation in a 10 mm sciatic nerve injury model, the conduits were evaluated for their neuro-regenerative potential through extensive electrophysiological studies and monitoring of gait pattern over a course of 12 months. Gross examination, histological and ultra-structure analyses of the conduits and the regenerated nerve were also performed to evaluate morphological regeneration of transected nerve. PASF nanocomposite conduits seeded with Schwann cell (cell seeded PASF) exhibited excellent nerve conduction velocity (NCV) (50 m s), compound muscle action potential (CMAP) (12.8 mV), motor unit potential (MUP) (124 μV), growth of healthy tissue along the nerve gap and thick myelination of axons 12 months after implantation indicating enhanced neuro-regeneration. The excellent functional recovery achieved by animals implanted with cell seeded PASF conduits (86.2% NCV; 80.00% CMAP; 76.07% MUP) are superior to outcomes achieved previously with similar electrically conductive conduits. We believe that the present study would encourage further research in developing electrically active neural implants using synthetic conducting polymers and the in vivo applications of the same.

摘要

本研究描述了基于聚苯胺-丝素蛋白(PASF)纳米复合材料的神经导管的制备及其随后在大鼠坐骨神经损伤模型中的植入,以促进周围神经再生。这是首个关于基于聚苯胺的神经导管的体内研究,描述了该导管在治疗周围神经损伤方面的安全性和有效性。纳米复合材料是通过静电纺丝丝素蛋白和聚苯胺的混合物合成的,其中观察到丝纳米纤维均匀地涂覆有聚苯胺纳米颗粒。随后,通过将静电纺丝片多次卷绕在不锈钢心轴上形成管状神经导管。对导管进行了体外理化性质以及与大鼠雪旺细胞相容性的表征。在 10mm 坐骨神经损伤模型中植入后,通过广泛的电生理研究和长达 12 个月的步态监测来评估导管的神经再生潜力。还对导管和再生神经进行了大体检查、组织学和超微结构分析,以评估横断神经的形态学再生。用雪旺细胞(细胞接种 PASF)接种的 PASF 纳米复合材料导管表现出优异的神经传导速度(NCV)(50m/s)、复合肌肉动作电位(CMAP)(12.8mV)、运动单位电位(MUP)(124μV)、神经间隙内健康组织的生长和轴突的厚髓鞘形成 12 个月后植入表明神经再生增强。与之前使用类似导电导管获得的结果相比,植入细胞接种 PASF 导管的动物获得了优异的功能恢复(86.2%NCV;80.00%CMAP;76.07%MUP)。我们相信,本研究将鼓励使用合成导电聚合物开发电活性神经植入物的进一步研究,并将其应用于体内。

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