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A nerve guidance conduit with topographical and biochemical cues: potential application using human neural stem cells

机译:具有地形和生化线索的神经引导导管:使用人类神经干细胞的潜在应用

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摘要

Despite major advances in the pathophysiological understanding of peripheral nerve damage, the treatment of nerve injuries still remains an unmet medical need. Nerve guidance conduits present a promising treatment option by providing a growth-permissive environment that 1) promotes neuronal cell survival and axon growth and 2) directs axonal extension. To this end, we designed an electrospun nerve guidance conduit using a blend of polyurea and poly-caprolactone with both biochemical and topographical cues. Biochemical cues were integrated into the conduit by functionalizing the polyurea with RGD to improve cell attachment. Topographical cues that resemble natural nerve tissue were incorporated by introducing intraluminal microchannels aligned with nanofibers. We determined that electrospinning the polymer solution across a two electrode system with dissolvable sucrose fibers produced a polymer conduit with the appropriate biomimetic properties. Human neural stem cells were cultured on the conduit to evaluate its ability to promote neuronal growth and axonal extension. The nerve guidance conduit was shown to enhance cell survival, migration, and guide neurite extension.
机译:尽管在对周围神经损伤的病理生理学理解方面取得了重大进展,但是神经损伤的治疗仍然是医学上尚未满足的需求。神经引导导管通过提供一种允许生长的环境来提供一种有前途的治疗选择,该环境允许1)促进神经元细胞存活和轴突生长,以及2)引导轴突伸展。为此,我们设计了一种电纺神经引导导管,该导管使用了聚脲和聚己内酯的混合物以及生化和地形学线索。通过用RGD对聚脲进行功能化以改善细胞附着,将生化线索整合到导管中。通过引入与纳米纤维对齐的管腔内微通道,可以融合类似于自然神经组织的地形线索。我们确定,用可溶解的蔗糖纤维将聚合物溶液静电纺丝穿过两电极系统产生了具有适当仿生特性的聚合物导管。将人类神经干细胞培养在导管上,以评估其促进神经元生长和轴突延伸的能力。已显示神经引导导管可增强细胞存活,迁移并引导神经突延伸。

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