Engineering Research Center in Biomaterials, Sichuan University, Chengdu, Sichuan 610064 People's Republic of China.
Biofabrication. 2020 May 12;12(3):035013. doi: 10.1088/1758-5090/ab860d.
Nerve tissues contain hierarchically ordered nerve fibers, while each of the nerve fibers has nano-oriented fibrous extracellular matrix and a core-shell structure of tubular myelin sheath with elongated axons encapsulated. Here, we report, for the first time, a ready approach to fabricate biomimetic nerve fibers which are oriented and have a core-shell structure to spatially encapsulate two types of cells, neurons and Schwann cells. A microfluidic system was designed and assembled, which contained a coaxial triple-channel chip and a stretching loading device. Alginate was used first to assist the fabrication, which was washed away afterwards. The orientation of the biomimetic nerve fibers was optimized by the control of the compositions of methacrylate hyaluronan and fibrin, together with the parameters of microfluidic shearing and external stretching. Also, neurons and Schwann cells, which were respectively located in the core and shell of the fibers, displayed advanced biologic functions, including neurogenesis and myelinating maturation. We demonstrate that the neural performance is relatively good, compared to that resulted from individually encapsulated in single-layer microfibers. The present study brings insights to fabricate biomimetic nerve fibers for their potential in neuroscience research and nerve regeneration. Moreover, the present methodology on the fabrication of oriented fibers with different types of cells separately encapsulated should be applicable to biomimetic constructions of various tissues.
神经组织包含层次有序的神经纤维，而每条神经纤维都具有纳米定向的纤维细胞外基质和管状髓鞘的核壳结构，其中包裹着拉长的轴突。在这里，我们首次报道了一种简单的方法来制备仿生神经纤维，这些纤维具有取向和核壳结构，可以空间包裹两种类型的细胞，即神经元和施万细胞。设计并组装了一个微流控系统，该系统包含一个同轴三通道芯片和一个拉伸加载装置。首先使用藻酸盐来辅助制备，然后将其洗掉。通过控制甲基丙烯酰化透明质酸和纤维蛋白的组成，以及微流剪切和外部拉伸的参数，优化了仿生神经纤维的取向。此外，分别位于纤维核心和壳层的神经元和施万细胞表现出了先进的生物学功能，包括神经发生和髓鞘成熟。与单独封装在单层微纤维中的结果相比，我们证明了神经性能相对较好。本研究为神经科学研究和神经再生中仿生神经纤维的制备提供了新的思路。此外，本研究中关于用不同类型的细胞分别封装制备取向纤维的方法应该适用于各种组织的仿生构建。
