Organ-on-a-chip technology can simulate the physiological and pathological microenvironment of tissues and organs in vitro, thus offering the potential of dispensing with animal models to predict the toxicity and efficacy of therapies. In this study, taking the alveolar microenvironment as a model, we developed a lung-on-a-chip with a poly(lactic-co-glycolic acid) (PLGA) electrospinning nanofiber membrane as the chip substrate and cell scaffold. The PLGA nanofiber membrane, with a controlled thickness of ∼3 μm, is porous and permeable to molecules, has good biocompatibility, and offers a means to simulate the alveolar respiratory membrane. On the chip, we carried out cell culture and co-culture of human non-small cell lung cancer cells (A549) and human fetal lung fibroblasts (HFL1), and evaluated gefitinib, an epidermal growth factor receptor (EGFR)-targeted anti-tumor drug. We further probed the possible sources of A549 cell drug resistance in the presence of HFL1 cells. In addition, we co-cultured A549, HFL1, and human umbilical vein endothelial cells (HUVECs), and found that A549 cells could lead to endothelial cell apoptosis or death, and then the occurrence of tumor invasion. This established lung-on-a-chip is simple, effective, and easy to operate. It is expected to have important applications in personalized treatment of lung tumors and to play a potential role in other clinical treatments and tissue engineering.

Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting our life quality. Air quality can be accessed by employing microchips that qualitatively and quantitatively determine the present gases and dust particles. The so-called particular matter 2.5 (PM2.5) values are of high importance, as such small particles can penetrate the human lung barrier and enter the blood system. There are cancer cases related to many air pollutants, and especially to PM2.5, contributing to exploding costs within the healthcare system. We focus on various current and potential future air pollutants, and propose solutions on how to protect our health against such dangerous substances. Recent developments in the Organ-on-Chip (OoC) technology can be used to study air pollution as well. OoC allows determination of pollutant toxicity and speeds up the development of novel pharmaceutical drugs.

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.

Viral infectious diseases remain a global public health problem. The rapid and widespread spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) has had a severe impact on the global economy and human activities, highlighting the vulnerability of humans to viral infectious diseases and the urgent need to develop new technologies and effective treatments. Organ-on-a-chip is an emerging technology for constructing the physiological and pathological microenvironment of human organs in vitro and has the advantages of portability, high throughput, low cost, and accurate simulation of the in vivo microenvironment. Indeed, organ-on-a-chip provides a low-cost alternative for investigating human organ physiology, organ diseases, toxicology, and drug efficacy. The lung is a main target organ of viral infection, and lung pathophysiology must be assessed after viral infection and treatment with antiviral drugs. This review introduces the construction of lung-on-a-chip and its related pathophysiological models, focusing on the in vitro simulation of viral infection and evaluation of antiviral drugs, providing a developmental direction for research and treatment of viral diseases.