外周神经损伤会引起感觉机能和运动机能障碍,严重影响患者日后的生活质量。中国科学院遗传与发育生物学研究所戴建武研究员领导的再生医学实验室与大连医科大学脑疾病研究所合作,在周围神经损伤后的再生研究中取得了重要进展。
损伤神经的再生与功能的恢复依赖于局部的微环境。研究表明,给予轴突再生正确有序的引导,并提供具有神经营养和保护功能的因子是促进再生关键。戴建武实验室研制了可引导并促进周围神经再生的有序功能生物支架材料,将有序胶原材料用化学交联的方法在表面包被对再生有促进作用层粘连蛋白,并符合可特异与层粘连蛋白靶向结合的基因工程重组人睫状神经营养因子(LBD-CNTF),来引导受损神经的再生,并有效发挥神经保护和促进再生的功能。
他们与合作者制备了大鼠坐骨神经横断模型,将这种有序功能生物材料填充到硅胶导管中连接神经断端。结果表明,这种功能材料可以引导神经纤维的有序生长,阻止再生神经纤维在管腔内发生弥散,明显加强了轴突,雪旺细胞的再生和神经纤维的髓鞘化。有效地促进了神经通路的重建与功能的恢复。
这项工作以戴建武实验室博士研究生曹佳妮为第一作者发表在Biomaterials上。该课题受到国家自然基金资助。(生物谷Bioon.com)
生物谷推荐原文出处:
Biomaterials DOI:10.1016/j.biomaterials.2011.02.020
The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats
Jiani Cao,Changkai Sun,Hui Zhao,Zhifeng Xiao,Bing Chen,Jian Gao,Tiezheng Zheng,Wei Wu,Shuang Wu,Jingyu Wang,Jianwu Dai
Nerve conduit provides a promising strategy for nerve injury repair in the peripheral nervous system (PNS). However, simply bridging the transected nerve with an empty conduit is hard to satisfy functional recovery. The regenerated axons may disperse during regeneration in the empty lumen, limiting the functional recovery. Our previous work had reported that linear ordered collagen scaffold (LOCS) could be used as a nerve guidance material. Here we cross-linked LOCS fibers with laminin which was a major component of the extracellular matrix in nervous system. Ciliary neurotrophic factor (CNTF) plays a critical role in peripheral nerve regeneration. But the lack of efficient CNTF delivery approach limits its clinical applications. To retain CNTF on the scaffold, a laminin binding domain (LBD) was fused to the N-terminal of CNTF. Compared with NAT-CNTF, LBD-CNTF exhibited specific laminin-binding ability and comparable neurotrophic bioactivity. We combined LBD-CNTF with the laminin modified LOCS fibers to construct a double-functional bio-scaffold. The functional scaffold was filled in silicon conduit and tested in the rat sciatic nerve transection model. Results showed that this functional biomaterial could guide the axon growth, retain more CNTF on the scaffolds and enhance the nerve regeneration as well as functional recovery.
Keywords: LOCS fibers; Laminin; LBD-CNTF; Nerve transection repair