Ferreira Daniel A, Conde João P, Rothbauer Mario, Ertl Peter, Granja Pedro L, Oliveira Carla
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Lab Chip. 2023 Jan 31;23(3):495-510. doi: 10.1039/d2lc01132h.
The lack of biomimetic models capable of reproducing the complex architecture and the dynamic environment of the gastric mucosa, delay the development of diagnostic and therapeutic tools. Recent advances in microengineering made possible the fabrication of bioinspired microdevices capable of replicating the physiological properties of an organ, inside a microfluidics chip. Herein, a bioinspired stomach-on-a-chip (SoC) device is described, supporting peristalsis-like motion and reconstituting organ-level epithelial architecture and function. The device simulates the upper epithelial interface, representing the three innermost layers of the gastric mucosa, namely the epithelial barrier, the basement membrane and the lamina propria. The dynamic environment imparted by mechanical actuation of the flexible on-chip cell culture substrate, was the main driver in the development of epithelial polarization and differentiation traits characteristic of the native gastric mucosa, and allowed partial recapitulation of gastric barrier function. These traits were not affected by the addition of a mesenchymal population to the system, which was able to remodel the surrounding extracellular matrix, nor by the potential epithelial-mesenchymal cross-talk. The engineered platform highlights the importance of addressing the mechanical microenvironment of the native organ, to potentiate an organ-level response of the artificial tissue. The proposed SoC represents an appealing tool in personalized medicine, with bio-relevance for the study of gastric diseases and an alternative to current animal models.
缺乏能够再现胃黏膜复杂结构和动态环境的仿生模型，延缓了诊断和治疗工具的开发。微工程学的最新进展使得在微流控芯片内制造能够复制器官生理特性的仿生微器件成为可能。在此，描述了一种仿生胃芯片（SoC）装置，其支持类似蠕动的运动，并重建器官水平的上皮结构和功能。该装置模拟上皮上层界面，代表胃黏膜的最内层三层，即上皮屏障、基底膜和固有层。通过对柔性芯片上细胞培养底物进行机械驱动赋予的动态环境，是胃黏膜天然上皮极化和分化特征发展的主要驱动力，并允许部分重现胃屏障功能。这些特征不受向系统中添加间充质群体的影响，间充质群体能够重塑周围的细胞外基质，也不受潜在的上皮-间充质相互作用的影响。该工程平台突出了考虑天然器官的机械微环境以增强人工组织器官水平反应的重要性。所提出的SoC代表了个性化医学中一种有吸引力的工具，对胃病研究具有生物相关性，并且是当前动物模型的一种替代方案。
