BASIC FIBROBLAST GROWTH-FACTOR RELEASED FROM SYNTHETIC GUIDANCE CHANNELS FACILITATES PERIPHERAL-NERVE REGENERATION ACROSS LONG NERVE GAPS
BASIC FIBROBLAST GROWTH-FACTOR RELEASED FROM SYNTHETIC GUIDANCE CHANNELS FACILITATES PERIPHERAL-NERVE REGENERATION ACROSS LONG NERVE GAPS
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DOI：
10.1002/jnr.490230306
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发表时间：
1989-07-01
影响因子：
4.2
通讯作者：
WINN, SR
中科院分区：
文献类型：
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作者：
AEBISCHER, P;SALESSIOTIS, AN;WINN, SR
碱性成纤维细胞生长因子(b-FGF)可促进包括背根神经节(DRG)细胞在内的各种类型神经元的体外存活和轴突伸展。α-1糖蛋白(α1-GP)是一种急性时相反应物，已被报道可促进体外培养的鸡背根神经节细胞的神经突起生长。在本研究中，我们研究了合成神经引导通道的能力，该通道释放持续控制量的b-FGF和/或α1-GP，以支持横断的周围神经在15 mm长的间隙中再生，这一距离不允许在传统的聚合管中再生。采用浸渍成型技术制备释放牛血清白蛋白(BSA)、细胞色素C、BSA和b-FGF、BSA和变性b-FGF、BSA和α1-GP或BSA、b-FGF和α1-GP的试管。体外蛋白质释放动力学研究表明，这些通道的蛋白质释放最初在第一天爆发，之后至少2周呈线性释放。体外研究表明，从聚合物中释放的b-成纤维细胞生长因子具有生物学活性，这是通过释放b-成纤维细胞生长因子的通道诱导PC12细胞突起延伸的能力来评估的。在活体研究中，不同类型的管子被用作神经引导通道，用于修复大鼠坐骨神经15 mm的神经缺口。移植4周后，只有释放b-Fgf或b-Fgf和α1-gp的管显示连接两个神经残端的再生电缆，其中含有神经束和有髓轴突和无髓轴突。结论：b-成纤维细胞生长因子促进周围神经再生，聚合管释放大分子为神经再生研究提供了工具。
Basic fibroblast growth factor (b-FGF) has been shown to enhance the in vitro survival and neurite extension of various types of neurons including dorsal root ganglia (DRG) cells. Alpha-1 glycoprotein (.alpha.1-GP), an acute phase reactant, has been reported to enhance the in vitro neuritic extensions of chick DRG cells. In the present study, we investigated the ability of synthetic nerve guidance channels, which release sustained controlled amounts of b-FGF and/or .alpha.1-GP, to support the regeneration of a transected peripheral nerve over a 15 mm long gap, a distance that does not permit regeneration in conventional polymeric tubes. Tubes releasing bovine serum albumin (BSA), cytochrome C, BSA and b-FGF, BSA and denaturated b-FGF, BSA and .alpha.1-GP, or BSA, b-FGF, and .alpha.1-GP were fabricated by a dip-molding technique. In vitro kinetic studies of protein release from these channels showed an initial burst during the 1st day, followed by a linear release for at least 2 weeks thereafter. In vitro studies indicated that the b-FGF released from the polymer was biologically active as assessed by the ability of channels releasing b-FGF to induce neurite extensions in PC12 cells. For in vivo studies, the various types of tubes were used as nerve guidance channels for the repair of a 15 mm nerve gap in the sciatic nerve of rats. Four weeks postimplantation, only the tubes releasing b-FGF or b-FGF and .alpha.1-GP displayed regenerated cables bridging both nerve stumps, which contained nerve fascicles with myelinated and unmyelinated axons. We conclude that b-FGF enhances peripheral nerve regeneration and that polymeric tubes releasing macromolecules provide a tool for the study of nerve regeneration.