Recent findings have highlighted an interconnection between intestinal microbiota and the brain, referred to as microbiota–gut–brain axis, and suggested that alterations in microbiota composition might affect brain functioning, also in Alzheimer’s disease. To investigate microbiota–gut–brain axis biochemical pathways, in this work we developed an innovative device to be used as modular unit in an engineered multi-organ-on-a-chip platform recapitulating in vitro the main players of the microbiota–gut–brain axis, and an innovative three-dimensional model of brain cells based on collagen/hyaluronic acid or collagen/poly(ethylene glycol) semi-interpenetrating polymer networks and β-amyloid precursor protein-Swedish mutant-expressing H4 cells, to simulate the pathological scenario of Alzheimer’s disease. We set up the culturing conditions, assessed cell response, scaled down the three-dimensional models to be hosted in the organ-on-a-chip device, and cultured them both in static and in dynamic conditions. The results suggest that the device and three-dimensional models are exploitable for advanced engineered models representing brain features also in Alzheimer’s disease scenario.

最近的发现凸显了肠道菌群与大脑之间的相互联系，称为菌群-肠-脑轴，并表明菌群组成的改变也可能影响大脑功能，在阿尔茨海默氏病中也是如此。为了研究微生物-肠-脑轴的生化途径，在这项工作中，我们开发了一种创新的设备，可在体外概括的工程化多芯片系统平台上用作模块化单元微生物-肠-脑轴的主要参与者，以及基于胶原/透明质酸或胶原/聚（乙二醇）半互穿聚合物网络和β-淀粉样前体蛋白-瑞典突变体的创新性脑细胞三维模型表达H4细胞，以模拟阿尔茨海默氏病的病理情况。我们设置了培养条件，评估了细胞反应，缩小了要在芯片上器官装置中托管的三维模型，并在静态和动态条件下进行了培养。结果表明，该设备和三维模型可用于代表阿尔茨海默氏病病例中大脑特征的高级工程模型。