Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
J Biomed Mater Res A. 2012 Jan;100(1):48-63. doi: 10.1002/jbm.a.33227. Epub 2011 Oct 4.
This study proposes a biodegradable nerve conduit containing genipin-cross-linked gelatin annexed with tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT) in peripheral nerve regeneration. Firstly, cytotoxicity tests revealed that the GGT-extracts were not toxic, and promoted the proliferation and neuronal differentiation of adipose tissue-derived stem cells (ADSCs). Secondly, the GGT composite film effectively supported ADSCs attachment and growth. Additionally, the GGT substrate was biocompatible with the neonatal rat sciatic nerve and produced a beneficial effect on peripheral nerve repair through in vitro tissue culture. Finally, the experiments in this study confirmed the effectiveness of a GGT/ADSCs nerve conduit as a guidance channel for repairing a 10-mm gap in a rat sciatic nerve. Eight weeks after implantation, the mean recovery index of compound muscle action potentials (CMAPs) was significantly different between the GGT/ADSCs and autografts groups (p < 0.05), both of which were significantly superior to the GGT group (p < 0.05). Furthermore, walking track analysis also showed a significantly higher sciatic function index (SFI) score (p < 0.05) and better toe spreading development in the GGT/ADSCs group than in the autograft group. Histological observations and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/ADSCs nerve conduits were similar to those of the autografts. The GGT nerve conduit offers a better scaffold for the incorporation of seeding undifferentiated ADSCs, and opens a new avenue to replace autologous nerve grafts for the rapid regeneration of damaged peripheral nerve tissues and an improved approach to patient care.
本研究提出了一种可生物降解的神经导管,其中包含了京尼平交联明胶与磷酸三钙陶瓷颗粒的复合物(京尼平-明胶-磷酸三钙,GGT),用于周围神经再生。首先,细胞毒性试验表明 GGT 提取物无毒性,并促进了脂肪组织来源的干细胞(ADSCs)的增殖和神经元分化。其次,GGT 复合膜有效地支持 ADSCs 的附着和生长。此外,GGT 基底与新生大鼠坐骨神经具有生物相容性,并通过体外组织培养对周围神经修复产生有益影响。最后,本研究中的实验证实了 GGT/ADSCs 神经导管作为引导通道修复大鼠坐骨神经 10mm 间隙的有效性。植入 8 周后,复合肌肉动作电位(CMAPs)的平均恢复指数在 GGT/ADSCs 组和自体移植物组之间有显著差异(p<0.05),且均显著优于 GGT 组(p<0.05)。此外,步态分析也显示 GGT/ADSCs 组的坐骨神经功能指数(SFI)评分明显更高(p<0.05),且足趾张开发育状况优于自体移植物组。组织学观察和免疫组织化学显示,GGT/ADSCs 神经导管中神经纤维的形态和分布模式与自体移植物相似。GGT 神经导管为接种未分化的 ADSCs 提供了更好的支架,为快速再生受损的周围神经组织和改善患者护理提供了一种替代自体神经移植的新途径。