Controlled release of nerve growth factor enhances sciatic nerve regeneration
Controlled release of nerve growth factor enhances sciatic nerve regeneration
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DOI：
10.1016/s0014-4886(03)00258-9
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发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Sakiyama-Elbert, SE
中科院分区：
文献类型：
--
作者：
Lee, AC;Yu, VM;Sakiyama-Elbert, SE
基于先前表明生长因子具有促进周围神经再生潜力的研究，我们开发了一种新型生长因子递送系统，以实现神经生长因子（NGF）的持续递送。该递送系统利用肝素固定NGF并减缓其从纤维蛋白基质中的扩散。此前已表明该系统在体外可促进神经突生长，在本研究中，我们评估了该递送系统通过导管促进神经再生的能力。我们测试了控制性NGF递送对13毫米大鼠坐骨神经缺损周围神经再生的影响。研究了含肝素的递送系统与三种剂量的NGF（5、20或50纳克/毫升）联合使用的情况，并将结果与阳性对照（同种异体移植物）和阴性对照（单独的纤维蛋白、单独的NGF以及空导管）进行了比较。术后6周采集神经进行组织形态计量学分析。递送系统组中的轴突再生呈现出明显的剂量依赖性效应。在导管水平和远端神经中，20纳克/毫升和50纳克/毫升的NGF剂量下的神经纤维总数与同种异体移植物（阳性对照）相比无统计学差异。本研究结果表明，采用一种能控制生长因子释放的新型递送系统可促进周围神经再生，这对促进短神经间隙的神经再生具有重要意义。（C）2003爱思唯尔科学（美国）。保留所有权利。
Based on previous studies demonstrating the potential of growth factors to enhance peripheral nerve regeneration, we developed a novel growth factor delivery system to provide sustained delivery of nerve growth factor (NGF). This delivery system uses heparin to immobilize NGF and slow its diffusion from a fibrin matrix. This system has been previously shown to enhance neurite outgrowth in vitro, and in this study, we evaluated the ability of this delivery system to enhance nerve regeneration through conduits. We tested the effect of controlled NGF delivery on peripheral nerve regeneration in a 13-mm rat sciatic nerve defect. The heparin-containing delivery system was studied in combination with three doses of NGF (5, 20, or 50 ng/mL) and the results were compared with positive controls (isografts) and negative controls (fibrin alone, NGF alone, and empty conduits). Nerves were harvested at 6 weeks postoperatively for histomorphometric analysis. Axonal regeneration in the delivery system groups revealed a marked dose-dependent effect. The total number of nerve fibers at both the nrid-conduit level and in the distal nerve showed no statistical difference for NGF doses at 20 and 50 ng/mL from the isograft (positive control). The results of this study demonstrate that the incorporation of a novel delivery system providing controlled release of growth factors enhances peripheral nerve regeneration and represents a significant contribution toward enhancing nerve regeneration across short nerve gaps. (C) 2003 Elsevier Science (USA). All rights reserved.