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使用源自人发的角蛋白生物材料促进周围神经快速再生。

The use of keratin biomaterials derived from human hair for the promotion of rapid regeneration of peripheral nerves.

作者信息

Sierpinski Paulina, Garrett Jeffrey, Ma Jianjun, Apel Peter, Klorig David, Smith Thomas, Koman L Andrew, Atala Anthony, Van Dyke Mark

机构信息

The Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA.

出版信息

Biomaterials. 2008 Jan;29(1):118-28. doi: 10.1016/j.biomaterials.2007.08.023. Epub 2007 Oct 4.

Abstract

The management of trauma-associated nerve defects is difficult because of the absence of autologous donor motor or sensory nerves. Pre-clinical development and clinical experience has shown that damaged nerves can be surgically repaired using a tubular conduit interposed across the defect. Acceptable patient outcomes are achieved so long as the gap distance does not exceed a few centimeters. Although research in animals has demonstrated that nerve repair can be facilitated across slightly larger gaps by introducing a biomaterial filler into the conduit lumen, these biomaterials are not typically "neuroinductive" (i.e. capable of acting directly on regenerative cells to enhance nerve tissue formation beyond clinical limits). Moreover, their use does not often result in functional recovery equivalent to nerve autograft, the clinical gold standard. Here we show that a biomaterial gel made from the proteins found in human hair can mediate a robust nerve regeneration response, in part through activation of Schwann cells. In vitro, keratins extracted from human hair enhance the activity of Schwann cells by a chemotactic mechanism, increase their attachment and proliferation, and up-regulate expression of important genes. Moreover, these characteristics translate to improved functional nerve recovery in an animal model. These results suggest that a biomaterial derived from human hair keratins is neuroinductive and can facilitate an outcome comparable to autograft in a nerve injury model.

摘要

由于缺乏自体供体运动或感觉神经,创伤相关神经缺损的治疗很困难。临床前研究和临床经验表明,使用横跨缺损处的管状导管可以对受损神经进行手术修复。只要间隙距离不超过几厘米,就能取得可接受的患者治疗效果。尽管动物研究表明,通过在导管腔内引入生物材料填充物,可以促进神经在稍大间隙处的修复,但这些生物材料通常不具有“神经诱导性”(即能够直接作用于再生细胞,促进神经组织形成超过临床极限)。此外,使用这些生物材料往往不会产生与临床金标准——神经自体移植相当的功能恢复效果。在此,我们表明,由人发中发现的蛋白质制成的生物材料凝胶可以介导强大的神经再生反应,部分是通过激活施万细胞实现的。在体外,从人发中提取的角蛋白通过趋化机制增强施万细胞的活性,增加其附着和增殖,并上调重要基因的表达。此外,这些特性在动物模型中转化为改善的功能性神经恢复。这些结果表明,源自人发角蛋白的生物材料具有神经诱导性,并且在神经损伤模型中可以促进与自体移植相当的治疗效果。

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