Biomimetic human lung-on-a-chip for modeling disease investigation

The lung is the primary respiratory organ of the human body and has a complicated and precise tissue structure. It comprises conductive airways formed by the trachea, bronchi and bronchioles, and many alveoli, the smallest functional units where gas-exchange occurs via the unique gas-liquid exchange interface known as the respiratory membrane. In vitro bionic simulation of the lung or its microenvironment, therefore, presents a great challenge, which requires the joint efforts of anatomy, physics, material science, cell biology, tissue engineering, and other disciplines. With the development of micromachining and miniaturization technology, the concept of a microfluidics-based organ-on-a-chip has received great attention. An organ-on-a-chip is a small cell-culture device that can accurately simulate tissue and organ functions in vitro and has the potential to replace animal models in evaluations of drug toxicity and efficacy. A lung-on-a-chip, as one of the first proposed and developed organs-on-a-chip, provides new strategies for designing a bionic lung cell microenvironment and for in vitro construction of lung disease models, and it is expected to promote the development of basic research and translational medicine in drug evaluation, toxicological detection, and disease model-building for the lung. This review summarizes current lungs-on-a-chip models based on the lung-related cellular microenvironment, including the latest advances described in studies of lung injury, inflammation, lung cancer, and pulmonary fibrosis. This model should see effective use in clinical medicine to promote the development of precision medicine and individualized diagnosis and treatment.