Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China.
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Adv Healthc Mater. 2023 Oct;12(26):e2300850. doi: 10.1002/adhm.202300850. Epub 2023 Jun 20.
Alveolar microenvironmental models are important for studying the basic biology of the alveolus, therapeutic trials, and drug testing. However, a few systems can fully reproduce the in vivo alveolar microenvironment including dynamic stretching and the cell-cell interface. Here, a novel biomimetic alveolus-on-a-chip microsystem is presented suitable for visualizing physiological breathing for simulating the 3D architecture and function of human pulmonary alveoli. This biomimetic microsystem contains an inverse opal structured polyurethane membrane that achieves real-time observation of mechanical stretching. In this microsystem, the alveolar-capillary barrier is created by alveolar type 2 (ATII) cells cocultured with vascular endothelial cells (ECs) on this membrane. Based on this microsystem, the phenomena of flattening and the tendency of differentiation in ATII cells are observed. The synergistic effects of mechanical stretching and ECs on the proliferation of ATII cells are also observed during the repair process following lung injury. These features indicate the potential of this novel biomimetic microsystem for exploring the mechanisms of lung diseases, which can provide future guidance concerning drug targets for clinical therapies.
肺泡微环境模型对于研究肺泡的基础生物学、治疗试验和药物测试非常重要。然而，很少有系统能够完全复制体内肺泡微环境，包括动态拉伸和细胞-细胞界面。在这里，提出了一种新颖的仿生肺泡芯片微系统，适用于可视化生理呼吸，模拟人类肺肺泡的 3D 结构和功能。这种仿生微系统包含具有反蛋白石结构的聚氨酯膜，可实现机械拉伸的实时观察。在这个微系统中，通过在该膜上共培养肺泡 II 型（ATII）细胞和血管内皮细胞（EC）来创建肺泡-毛细血管屏障。基于这个微系统，可以观察到 ATII 细胞的扁平化和分化趋势。在肺损伤后的修复过程中，还观察到机械拉伸和 EC 对 ATII 细胞增殖的协同作用。这些特征表明，这种新型仿生微系统在探索肺部疾病机制方面具有潜力，可为临床治疗的药物靶点提供未来指导。
