The Effect of Pulse-Released Nerve Growth Factor from Genipin-Crosslinked Gelatin in Schwann Cell-Seeded Polycaprolactone Conduits on Large-Gap Peripheral Nerve Regeneration

The Effect of Pulse-Released Nerve Growth Factor from Genipin-Crosslinked Gelatin in Schwann Cell-Seeded Polycaprolactone Conduits on Large-Gap Peripheral Nerve Regeneration
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DOI:
10.1089/ten.tea.2007.0342
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发表时间:
2009-03-01
影响因子:
4.1
通讯作者:
Chang, Chen-Jung
Chang, Chen-Jung
中科院分区:
医学3区
文献类型:
--
作者:
Chang, Chen-Jung

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研究了京尼平交联明胶脉冲释放神经生长因子(NGF)在聚己内酯(PCL)导管内不同的滞后时间对周围神经大间隙修复的影响。在这项研究中,10%(w/v)明胶与NGF混合,与0%,0.1%,0.5%和1%(w/v)京尼平交联,然后吸入PCL导管壁。这些控释神经导管分别命名为NCL(非交联)、LCL(低交联)、MCL(中等交联)和HCL(高交联)。NGF的释放特征表现为4条明显的曲线,即5d内的初始爆发、5-20 d的脉冲释放、10-25 d的脉冲释放和稳定释放。各组培养后PC 12细胞突起生长均显示其释放的NGF具有生物活性。最后,将9 × 103个雪旺细胞接种到控释导管中。导管用于桥接15 mm大鼠坐骨神经缺损,并将结果与同系移植物(对照组)进行比较。植入8周后,形态学分析显示,LCL,MCL和HCL组在有髓轴突的数量和面积方面与自体移植治疗相似。LCL组虽然不显著,但显示出具有最高的有髓轴突计数的趋势。因此,比较NCL、MCL和LCL组之间不同的NGF释放特征,我们得出结论,在LCL组中,在桥接15 mm的周围神经损伤时,需要在5-10天时高浓度的NGF。
Different lag-time of pulse-released nerve growth factor (NGF) from genipin-crosslinked gelatin within polycaprolactone (PCL) conduits was evaluated in large-gap peripheral nerve repair. In this study, 10% (w/v) gelatin was mixed with NGF, crosslinked with 0%, 0.1%, 0.5%, and 1% (w/v) genipin, and then sucked into the wall of PCL conduits. These controlled-release nerve conduits were named NCL (non-crosslink), LCL (low crosslink), MCL (medium crosslink), and HCL (high crosslink), respectively. The NGF releasing character showed four distinctive curves, including initial burst within 5 days, pulse releasing at 5-20 days, pulse releasing at 10-25 days, and steadily releasing. The bioactivity of the released NGF was shown by neurite outgrowth of PC12 cells after culturing in all groups. Finally, the controlled-release conduits were seeded with 9 x 10(3) Schwann cells. Conduits were used to bridge a 15-mm rat sciatic nerve defect, and the results were compared with the isografts (control group). Eight weeks after implantation, morphological analysis revealed that LCL, MCL, and HCL groups were similar to autograft treatment in the numbers and area of myelinated axons. The LCL group, although insignificant, showed a trend to have the highest myelinated axon counts of the conduit-treated groups. Thus, comparing the different NGF release characteristics among NCL, MCL, and LCL groups, we concluded that a high concentration of NGF at 5-10 days in LCL groups is needed in bridging a 15-mm peripheral nerve injury.