Lee Annie C, Yu Vivian M, Lowe James B, Brenner Michael J, Hunter Daniel A, Mackinnon Susan E, Sakiyama-Elbert Shelly E
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Exp Neurol. 2003 Nov;184(1):295-303. doi: 10.1016/s0014-4886(03)00258-9.
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 mid-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.
基于先前的研究表明生长因子具有促进周围神经再生的潜力，我们开发了一种新型的生长因子递送系统，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。该系统先前已被证明能在体外促进神经突生长，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。我们在13毫米大鼠坐骨神经缺损模型中测试了可控NGF递送对周围神经再生的影响。将含肝素的递送系统与三种剂量的NGF（5、20或50 ng/mL）联合研究，并将结果与阳性对照（同基因移植）和阴性对照（单独的纤维蛋白、单独的NGF和空导管）进行比较。术后6周收获神经进行组织形态计量学分析。递送系统组的轴突再生显示出明显的剂量依赖性效应。在导管中部水平和远端神经中，20和50 ng/mL剂量的NGF与同基因移植（阳性对照）相比，神经纤维总数无统计学差异。本研究结果表明，采用提供生长因子控释的新型递送系统可促进周围神经再生，这对跨越短神经间隙增强神经再生具有重要意义。
