Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 300044, Taiwan.
Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland, 20742, USA.
Lab Chip. 2024 Mar 26;24(7):1887-1902. doi: 10.1039/d3lc00507k.
Microfluidics-based organs-on-a-chip offer a promising method for dynamic and 3-dimensional (3D) cell culture to evaluate the cell behaviors within the biomimetic environment. The purpose of this study was to establish neural network connections in a 3D neural stem cell (NSC)-based system with an interstitial level of flow for simulating the brain microenvironment toward a dynamic amyloid-β (Aβ) induced neuronal toxic model on a chip and to compare the biological effects and neurite dysfunction between static and dynamic systems. The brain-on-a-chip system consisted of an impedance analyzing layer, a structured well with a connected channel, and an interface coating with polypeptide films fabricated with modification based on our previous study. The cytotoxicity and percentage of neuron/astrocyte differentiation were all compared in both static and dynamic brain-on-a-chip systems. Reactive oxygen species production, neuron marker expression and neurotransmitter-acetylcholine release were all compared to evaluate functional neurite losses in both static and dynamic systems with/without Aβ addition. Moreover, real-time impedance recording was used to consecutively monitor the neurite connection/disconnection in both static and dynamic brain-on-a-chip systems. The NSC-based dynamic brain-on-a-chip may enable the application of different neurodegenerative disease models for pathogenesis studies, drug discovery and novel therapeutic method development.
基于微流控的器官芯片为动态和三维（3D）细胞培养提供了一种很有前途的方法，可用于评估仿生环境中细胞的行为。本研究的目的是在基于神经干细胞（NSC）的系统中建立神经网络连接，该系统具有间质水平的流动，以模拟大脑微环境，在芯片上建立动态淀粉样蛋白-β（Aβ）诱导的神经元毒性模型，并比较静态和动态系统之间的生物学效应和神经突功能障碍。脑芯片系统由阻抗分析层、带有连接通道的结构化井和基于我们之前研究的多肽膜修饰的接口涂层组成。在静态和动态脑芯片系统中均比较了细胞毒性和神经元/星形胶质细胞分化的百分比。比较了活性氧（ROS）的产生、神经元标志物的表达和神经递质乙酰胆碱的释放，以评估有/无 Aβ添加时静态和动态系统中功能性神经突损失。此外，还使用实时阻抗记录连续监测静态和动态脑芯片系统中神经突的连接/断开。基于 NSC 的动态脑芯片可能使不同的神经退行性疾病模型能够应用于发病机制研究、药物发现和新的治疗方法开发。
