Fendler Cornelius, Denker Christian, Harberts Jann, Bayat Parisa, Zierold Robert, Loers Gabriele, Münzenberg Markus, Blick Robert H
Center for Hybrid Nanostructures (CHyN), Universität Hamburg, Luruper Chaussee 149, Hamburg, 22761, Germany.
Institute of Physics, University of Greifswald, Felix-Hausdorff-Str. 6, Greifswald, 17489, Germany.
Adv Biosyst. 2019 May;3(5):e1800329. doi: 10.1002/adbi.201800329. Epub 2019 Mar 7.
While modern day integrated electronic circuits are essentially designed in a 2D fashion, the brain can be regarded as a 3D circuit. The thus enhanced connectivity enables much more complex signal processing as compared to conventional 2D circuits. Recent technological advances in the development of nano/microscale 3D structuring have led to the development of artificial neuron culturing platforms, which surpass the possibilities of classical 2D cultures. In this work, in vitro culturing of neuronal networks is demonstrated by determining predefined pathways through topological and chemical neurite guiding. Tailor-made culturing substrates of microtowers and freestanding microtubes are fabricated using direct laser writing by two-photon polymerization. The first scaffold design that allows for site-specific cell attachment and directed outgrowth of single neurites along defined paths that can be arranged freely in all dimensions, to build neuronal networks with low cell density, is presented. The neurons cultured in the scaffolds show characteristic electrophysiological properties of vital cells after 10 d in vitro. The introduced scaffold design offers a promising concept for future complex neuronal network studies on defined neuronal circuits with tailor-made design specific neurite connections beyond 2D.
虽然现代集成电子电路本质上是以二维方式设计的，但大脑可被视为三维电路。与传统二维电路相比，这种增强的连通性能够实现更复杂的信号处理。纳米/微米级三维结构开发方面的最新技术进展催生了人工神经元培养平台，其超越了传统二维培养的可能性。在这项工作中，通过拓扑和化学神经突引导确定预定义路径，展示了神经网络的体外培养。利用双光子聚合直接激光写入技术制造了微塔和独立微管的定制培养底物。提出了第一种支架设计，该设计允许细胞在特定位置附着，并使单个神经突沿着可在所有维度自由排列的定义路径定向生长，以构建低细胞密度的神经网络。在支架中培养的神经元在体外培养10天后显示出活细胞的特征性电生理特性。所引入的支架设计为未来关于具有定制设计特定神经突连接的定义神经元回路的复杂神经网络研究提供了一个有前景的概念，超越了二维研究。
