The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats
The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats
复制标题
使用载有层粘连蛋白结合睫状神经营养因子的层粘连蛋白修饰的线性有序胶原支架用于大鼠坐骨神经再生
DOI：
10.1016/j.biomaterials.2011.02.020
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发表时间：
2011-06-01
期刊：
影响因子：
14
通讯作者：
Dai, Jianwu
中科院分区：
文献类型：
--
作者：
Cao, Jiani;Sun, Changkai;Dai, Jianwu
神经导管为周围神经系统（PNS）的神经损伤修复提供了一种很有前途的策略。然而，单纯用空导管桥接横断的神经很难满足功能恢复。再生的轴突可能在空腔再生期间分散，限制功能恢复。我们前期的工作报道了线性有序胶原支架（LOCS）可以作为神经导向材料。本实验将神经系统细胞外基质的主要成分层粘连蛋白与LOCS纤维交联。睫状神经营养因子（CNTF）在周围神经再生中起关键作用。但由于缺乏有效的CNTF递送途径，限制了其临床应用。为了将CNTF保留在支架上，将层粘连蛋白结合结构域（LBD）融合到CNTF的N-末端。与NAT-CNTF相比，LBD-CNTF具有特异的层粘连蛋白结合能力和相当的神经营养活性。我们将LBD-CNTF与层粘连蛋白修饰的LOCS纤维结合，构建了一种双功能生物支架。将该支架填充于硅导管中，并在大鼠坐骨神经横断模型上进行测试。结果表明，这种功能性生物材料能引导轴突生长，并能使更多的CNTF保留在支架上，促进神经再生和功能恢复。(C)2011爱思唯尔有限公司保留所有权利。
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. (C) 2011 Elsevier Ltd. All rights reserved.