使用层粘连蛋白修饰的线性有序胶原支架负载层粘连蛋白结合睫状神经营养因子促进大鼠坐骨神经再生。

The use of laminin modified linear ordered collagen scaffolds loaded with laminin-binding ciliary neurotrophic factor for sciatic nerve regeneration in rats.

机构信息

Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China.

出版信息

Biomaterials. 2011 Jun;32(16):3939-48. doi: 10.1016/j.biomaterials.2011.02.020.

Abstract

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.

摘要

神经导管为外周神经系统 (PNS) 的神经损伤修复提供了一种很有前途的策略。然而,仅仅用空导管桥接断裂的神经很难满足功能恢复的要求。再生轴突在空管腔中再生时可能会分散,从而限制功能恢复。我们之前的工作已经报道线性有序胶原支架 (LOCS) 可用作神经引导材料。在这里,我们用层粘连蛋白交联 LOCS 纤维,层粘连蛋白是神经系统细胞外基质的主要成分之一。睫状神经营养因子 (CNTF) 在周围神经再生中起着至关重要的作用。但缺乏有效的 CNTF 传递方法限制了其临床应用。为了保留支架上的 CNTF,将层粘连蛋白结合结构域 (LBD) 融合到 CNTF 的 N 端。与 NAT-CNTF 相比,LBD-CNTF 表现出特定的层粘连蛋白结合能力和相当的神经营养生物活性。我们将 LBD-CNTF 与层粘连蛋白修饰的 LOCS 纤维结合,构建了一种具有双重功能的生物支架。功能性支架填充在硅导管中,并在大鼠坐骨神经横断模型中进行了测试。结果表明,这种功能性生物材料可以引导轴突生长,在支架上保留更多的 CNTF,并促进神经再生和功能恢复。

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