Development of two-photon polymerised scaffolds for optical interrogation and neurite guidance of human iPSC-derived cortical neuronal networks

Development of two-photon polymerised scaffolds for optical interrogation and neurite guidance of human iPSC-derived cortical neuronal networks
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DOI:
10.1039/c9lc01209e
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发表时间:
2020-05-21
期刊:
影响因子:
6.1
通讯作者:
Rafailov, E. U.
Rafailov, E. U.
中科院分区:
工程技术1区
文献类型:
--
作者:
Crowe, J. A.;El-Tamer, A.;Rafailov, E. U.

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人类诱导多能干细胞(iPSC)领域的最新进展已经导致用于体外研究的人类神经元细胞模型的有效产生。这有可能使活的人类细胞和网络功能的理解,否则是不可能的。然而,一个主要的挑战是产生可重复的神经网络,以及在单细胞水平上进行询问和记录的能力。一个有前途的援助是使用生物材料支架,这将使神经元网络的发展和指导生理相关的架构和维度。最佳的支架材料需要以亚微米分辨率精确制造,光学透明,并且生物相容。双光子聚合(2PP)可以精确地制造三维结构。在这项研究中,我们报告了两种支持人iPSC衍生的神经祖细胞生长和分化为功能性神经元网络的生物材料的鉴定。此外,这些材料可以被图案化以诱导神经元过程的对齐,并能够对单个细胞进行光学询问。因此,具有定制形貌的2PP支架提供了一种有效的方法,用于产生限定的体外人类神经网络,以应用于影响神经突引导和复杂网络活性。
Recent progress in the field of human induced pluripotent stem cells (iPSCs) has led to the efficient production of human neuronal cell models for in vitro study. This has the potential to enable the understanding of live human cellular and network function which is otherwise not possible. However, a major challenge is the generation of reproducible neural networks together with the ability to interrogate and record at the single cell level. A promising aid is the use of biomaterial scaffolds that would enable the development and guidance of neuronal networks in physiologically relevant architectures and dimensionality. The optimal scaffold material would need to be precisely fabricated with submicron resolution, be optically transparent, and biocompatible. Two-photon polymerisation (2PP) enables precise microfabrication of three-dimensional structures. In this study, we report the identification of two biomaterials that support the growth and differentiation of human iPSC-derived neural progenitors into functional neuronal networks. Furthermore, these materials can be patterned to induce alignment of neuronal processes and enable the optical interrogation of individual cells. 2PP scaffolds with tailored topographies therefore provide an effective method of producing defined in vitro human neural networks for application in influencing neurite guidance and complex network activity.