Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Tissue Eng Part A. 2011 May;17(9-10):1263-75. doi: 10.1089/ten.TEA.2010.0507. Epub 2011 Feb 3.
The aim of this study was to evaluate the long-term effect of localized growth factor delivery on sciatic nerve regeneration in a critical-size (> 1 cm) peripheral nerve defect. Previous work has demonstrated that bioactive proteins can be encapsulated within double-walled, poly(lactic-co-glycolic acid)/poly(lactide) microspheres and embedded within walls of biodegradable polymer nerve guides composed of poly(caprolactone). Within this study, nerve guides containing glial cell line-derived neurotrophic factor (GDNF) were used to bridge a 1.5-cm defect in the male Lewis rat for a 16-week period. Nerve repair was evaluated through functional assessment of joint angle range of motion using video gait kinematics, gastrocnemius twitch force, and gastrocnemius wet weight. Histological evaluation of nerve repair included assessment of Schwann cell and neurofilament location with immunohistochemistry, evaluation of tissue integration and organization throughout the lumen of the regenerated nerve with Masson's trichrome stain, and quantification of axon fiber density and g-ratio. Results from this study showed that the measured gastrocnemius twitch force in animals treated with GDNF was significantly higher than negative controls and was not significantly different from the isograft-positive control group. Histological assessment of explanted conduits after 16 weeks showed improved tissue integration within GDNF releasing nerve guides compared to negative controls. Nerve fibers were present across the entire length of GDNF releasing guides, whereas nerve fibers were not detectable beyond the middle region of negative control guides. Therefore, our results support the use of GDNF for improved functional recovery above negative controls following large axonal defects in the peripheral nervous system.
本研究旨在评估局部生长因子输送对超过 1cm （临界尺寸）周围神经缺损的坐骨神经再生的长期影响。先前的工作已经证明，生物活性蛋白可以被包裹在双层聚（乳酸-共-羟基乙酸）/聚乳酸微球中，并嵌入由聚己内酯组成的可生物降解聚合物神经导管的壁内。在本研究中，使用含有胶质细胞源性神经营养因子（GDNF）的神经导管桥接雄性 Lewis 大鼠 1.5cm 的缺损，持续 16 周。通过使用视频步态运动学、比目鱼肌抽搐力和比目鱼肌湿重对关节角度运动范围的功能评估来评估神经修复。神经修复的组织学评估包括用免疫组织化学评估施万细胞和神经丝的位置，用 Masson 三色染色评估再生神经管腔中组织的整合和组织，以及定量轴突纤维密度和 g 比。本研究的结果表明，用 GDNF 治疗的动物的比目鱼肌抽搐力明显高于阴性对照组，与同种异体阳性对照组无显著差异。16 周后对植入导管的组织学评估显示，与阴性对照组相比，GDNF 释放神经导管的组织整合得到改善。神经纤维存在于 GDNF 释放导管的整个长度上，而在阴性对照导管的中间区域之外则无法检测到神经纤维。因此，我们的结果支持在周围神经系统大轴突缺陷后使用 GDNF 来改善功能恢复，优于阴性对照。
