Joung Daeha, Truong Vincent, Neitzke Colin C, Guo Shuang-Zhuang, Walsh Patrick J, Monat Joseph R, Meng Fanben, Park Sung Hyun, Dutton James R, Parr Ann M, McAlpine Michael C
Department of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Department of Neurosurgery, Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Adv Funct Mater. 2018 Sep 26;28(39). doi: 10.1002/adfm.201801850. Epub 2018 Aug 9.
A bioengineered spinal cord is fabricated via extrusion-based multi-material 3D bioprinting, in which clusters of induced pluripotent stem cell (iPSC)-derived spinal neuronal progenitor cells (sNPCs) and oligodendrocyte progenitor cells (OPCs) are placed in precise positions within 3D printed biocompatible scaffolds during assembly. The location of a cluster of cells, of a single type or multiple types, is controlled using a point-dispensing printing method with a 200 μm center-to-center spacing within 150 μm wide channels. The bioprinted sNPCs differentiate and extend axons throughout microscale scaffold channels, and the activity of these neuronal networks is confirmed by physiological spontaneous calcium flux studies. Successful bioprinting of OPCs in combination with sNPCs demonstrates a multicellular neural tissue engineering approach, where the ability to direct the patterning and combination of transplanted neuronal and glial cells can be beneficial in rebuilding functional axonal connections across areas of central nervous system (CNS) tissue damage. This platform can be used to prepare novel biomimetic, hydrogel-based scaffolds modeling complex CNS tissue architecture and harnessed to develop new clinical approaches to treat neurological diseases, including spinal cord injury.
通过基于挤出的多材料3D生物打印制造生物工程脊髓,其中在组装过程中,诱导多能干细胞(iPSC)衍生的脊髓神经元祖细胞(sNPC)和少突胶质细胞祖细胞(OPC)簇被放置在3D打印的生物相容性支架内的精确位置。使用点分配打印方法控制单一类型或多种类型细胞簇的位置,在150μm宽的通道内中心间距为200μm。生物打印的sNPC在整个微观尺度支架通道中分化并延伸轴突,并且通过生理自发钙通量研究证实了这些神经网络的活性。OPC与sNPC的成功生物打印展示了一种多细胞神经组织工程方法,其中指导移植的神经元和胶质细胞的图案化和组合的能力在重建中枢神经系统(CNS)组织损伤区域的功能性轴突连接方面可能是有益的。该平台可用于制备模拟复杂CNS组织结构的新型仿生水凝胶基支架,并用于开发治疗包括脊髓损伤在内的神经系统疾病的新临床方法。