Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
Biomaterials. 2012 Jan;33(1):59-71. doi: 10.1016/j.biomaterials.2011.09.030. Epub 2011 Oct 17.
Various attempts have been made to develop artificial conduits for nerve repair, but with limited success. We describe here conduits made from Bombyx mori regenerated silk protein, and containing luminal fibres of Spidrex(®), a silk-based biomaterial with properties similar to those of spider silk. Assessment in vitro demonstrated that Spidrex(®) fibres support neurite outgrowth. For evaluation in vivo, silk conduits 10 mm in length and containing 0, 100, 200 or 300 luminal Spidrex(®) fibres, were implanted to bridge an 8 mm gap in the rat sciatic nerve. At 4 weeks, conduits containing 200 luminal Spidrex(®) fibres (PN200) supported 62% and 59% as much axon growth as autologous nerve graft controls at mid-conduit and distal nerve respectively. Furthermore, Spidrex(®) conduits displayed similar Schwann cell support and macrophage response to controls. At 12 weeks, animals implanted with PN200 conduits showed similar numbers of myelinated axons (81%) to controls, similar gastrocnemius muscle innervation, and similar hindpaw stance assessed by Catwalk footprint analysis. Plantar skin innervation was 73% of that of controls. PN200 Spidrex(®) conduits were also effective at bridging longer (11 and 13 mm) gaps. Our results show that Spidrex(®) conduits promote excellent axonal regeneration and function recovery, and may have potential for clinical application.
已经有许多尝试来开发用于神经修复的人工导管,但效果有限。我们在这里描述了一种由桑蚕再生丝蛋白制成的导管,其中包含 Spidrex(®)的内腔纤维,Spidrex(®)是一种具有类似蜘蛛丝性能的丝基生物材料。体外评估表明,Spidrex(®)纤维支持神经突生长。为了进行体内评估,植入了长 10 毫米、内腔含有 0、100、200 或 300 根 Spidrex(®)纤维的丝导管,以桥接大鼠坐骨神经 8 毫米的间隙。在 4 周时,含有 200 根内腔 Spidrex(®)纤维的导管(PN200)在导管中部和远端神经分别支持 62%和 59%的轴突生长,与自体神经移植物对照相似。此外,Spidrex(®)导管显示出与对照相似的施万细胞支持和巨噬细胞反应。在 12 周时,植入 PN200 导管的动物显示出与对照相似数量的有髓轴突(81%),相似的比目鱼肌神经支配,以及通过 Catwalk 足迹分析评估的相似后足姿势。足底皮肤神经支配为对照的 73%。PN200 Spidrex(®)导管在桥接更长(11 和 13 毫米)间隙时也有效。我们的结果表明,Spidrex(®)导管促进了优异的轴突再生和功能恢复,并且可能具有临床应用的潜力。