Altinova Haktan, Möllers Sven, Führmann Tobias, Deumens Ronald, Bozkurt Ahmet, Heschel Ingo, Damink Leon H H Olde, Schügner Frank, Weis Joachim, Brook Gary A
Department of Neurology, Uniklinik Aachen, Aachen, Germany; Department of Neurosurgery, Evangelic Hospital Bethel, Bielefeld, Germany; Institute for Neuropathology, Uniklinik Aachen, Aachen, Germany.
Department of Neurology, Uniklinik Aachen, Aachen, Germany; RNL Europe GmbH, Kleinmachnow, Germany.
Brain Res. 2014 Oct 17;1585:37-50. doi: 10.1016/j.brainres.2014.08.041. Epub 2014 Sep 3.
The formation of cystic cavitation following severe spinal cord injury (SCI) constitutes one of the major barriers to successful axonal regeneration and tissue repair. The development of bioengineered scaffolds that assist in the bridging of such lesion-induced gaps may contribute to the formulation of combination strategies aimed at promoting functional tissue repair. Our previous in vitro investigations have demonstrated the directed axon regeneration and glial migration supporting properties of microstructured collagen scaffold that had been engineered to possess mechanical properties similar to those of spinal cord tissues. Here, the effect of implanting the longitudinally orientated scaffold into unilateral resection injuries (2mm long) of the mid-cervical lateral funiculus of adult rats has been investigated using behavioural and correlative morphological techniques. The resection injuries caused an immediate and long lasting (up to 12 weeks post injury) deficit of food pellet retrieval by the ipsilateral forepaw. Implantation of the orientated collagen scaffold promoted a significant improvement in pellet retrieval by the ipsilateral forepaw at 6 weeks which continued to improve up to 12 weeks post injury. In contrast, implantation of a non-orientated gelatine scaffold did not result in significant functional improvement. Surprisingly, the improved motor performance was not correlated with the regeneration of lesioned axons through the implanted scaffold. This observation supports the notion that biomaterials may support functional recovery by mechanisms other than simple bridging of the lesion site, such as the local sprouting of injured, or even non-injured fibres.
严重脊髓损伤(SCI)后形成的囊性空洞是轴突成功再生和组织修复的主要障碍之一。开发有助于桥接此类损伤诱导间隙的生物工程支架可能有助于制定旨在促进功能性组织修复的联合策略。我们之前的体外研究表明,经过工程设计使其具有与脊髓组织相似机械性能的微结构胶原支架具有定向轴突再生和支持神经胶质细胞迁移的特性。在此,我们使用行为学和相关形态学技术研究了将纵向定向支架植入成年大鼠颈中侧索单侧切除损伤(2毫米长)后的效果。切除损伤导致同侧前爪立即且长期(直至损伤后12周)出现食物颗粒抓取缺陷。植入定向胶原支架后,同侧前爪在6周时的颗粒抓取有显著改善,且在损伤后12周持续改善。相比之下,植入非定向明胶支架并未导致显著的功能改善。令人惊讶的是,运动功能的改善与损伤轴突通过植入支架的再生无关。这一观察结果支持了这样一种观点,即生物材料可能通过除简单桥接损伤部位之外的其他机制来支持功能恢复,例如受损甚至未受损纤维的局部发芽。