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A Novel Internal Fixator Device for Peripheral Nerve Regeneration

机译:一种新型的周围神经再生内固定器

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摘要

Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension—traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration.
机译:周围神经损伤(尤其是横断神经)的恢复很少能完全完成,从而导致运动功能受损,感觉丧失和慢性疼痛,以及不适当的自主神经反应,严重损害生活质量。因此,增强周围神经修复的策略具有很高的临床重要性。张力是神经元生长和功能的关键决定因素。体外和体内实验表明,中等程度的施加张力(应变)可以促进轴突生长;反之亦然。然而,很少有周围神经修复的策略强调受伤神经的机械环境。为了开发更有效的神经再生策略,我们演示了新型模块化神经延长装置的设计,制造和实施,该装置可施加适度的拉伸载荷,并与现有的基于支架的神经修复组织工程策略并行。这个概念将使神经能够在两种重叠的神经伸展方式中进行再生,即通过轴突向外生长进入支架的传统伸展和在近端神经完整区域的伸展,例如在生长或肢体延长过程中发生的伸展。自定尺寸的硅树脂神经袖套可抓握神经残端而不会打滑,并且通过驱动伸缩式内固定器使神经变形。安装在伸缩杆上的聚(乳酸共乙醇酸)(PLGA)构建体与神经残端并置,以引导轴突生长。使用直接接触和提取方法将神经元细胞暴露于PLGA,就细胞形态和生存力而言,它们没有细胞毒性作用的迹象。我们确认了在坐骨神经间隙内植入和启动我们的装置的可行性,并观察到装置植入后的轴突生长。我们设备的成功制造和实施为检查机械对神经再生的影响提供了一种新颖的方法。

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