Bridging peripheral nerve defects with a tissue engineered nerve graft composed of an in vitro cultured nerve equivalent and a silk fibroin-based scaffold.
Bridging peripheral nerve defects with a tissue engineered nerve graft composed of an in vitro cultured nerve equivalent and a silk fibroin-based scaffold.
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DOI：
10.1016/j.biomaterials.2012.02.008
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发表时间：
2012-05
期刊：
影响因子：
14
通讯作者：
Xin Tang;Chengbin Xue;Yaxian Wang;F. Ding;Yumin Yang;X. Gu
中科院分区：
文献类型：
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作者：
Xin Tang;Chengbin Xue;Yaxian Wang;F. Ding;Yumin Yang;X. Gu
组织工程神经移植物被认为是一种有前途的替代自体神经移植物用于周围神经修复。这两种类型的神经移植物之间的差异主要在于它们建立的再生微环境。为了构建理想的组织工程化神经移植物，因此需要开发一种更好的方法来将生物化学信号引入神经支架中，而不是单独或联合使用支持细胞和生长因子。在这里，我们使用背根神经节和雪旺细胞的共培养系统来创建体外形成的神经等同物，其被引入到基于丝素蛋白的支架中以提供组织工程神经移植物（TENG）。在4周和12周后植入TENG桥接大鼠坐骨神经10 mm长的缺损，进行组织学和功能评估以及Western blot分析，以评估TENG对周围神经再生的影响。我们发现，在神经再生的早期阶段，TENG显著促进轴突生长，并上调N-cadherin和PMP 22的表达。神经移植后12周，TENG产生了进一步改善的神经再生和功能恢复的结果，这比丝素蛋白基支架更接近自体神经移植物。将体外培养的神经等效物引入支架中可能有助于建立神经再生的天然微环境。
Tissue engineered nerve grafts are considered as a promising alternative to autologous nerve grafts used for peripheral nerve repair. The differences between these two types of nerve grafts are mainly in the regenerative microenvironment established by them. To construct ideal tissue engineered nerve grafts, it is therefore required to develop a better way to introduce biochemical cues into a neural scaffold, as compared to single or combined use of support cells and growth factors. Here, we used a co-culture system of dorsal root ganglia and Schwann cells to create an in vitro formed nerve equivalent, which was introduced into a silk fibroin-based scaffold to furnish a tissue engineered nerve graft (TENG). At 4- and 12- weeks after the TENG was implanted to bridge a 10-mm-long sciatic nerve defect in rats, histological and functional assessments as well as Western blot analysis were performed to evaluate the influences of the TENG on peripheral nerve regeneration. We found that at an early stage of nerve regeneration, the TENG significantly accelerated axonal growth, and up-regulated expressions of N-cadherin and PMP22. Twelve weeks after nerve grafting, the TENG produced a further improved outcome of nerve regeneration and functional recovery, which was more close to that of the autologous nerve graft than that of the silk fibroin-based scaffold. The introduction of an in vitro cultured nerve equivalent into a scaffold might contribute to establishing a native-like microenvironment for nerve regeneration.