ABSTRACT
Disease models that can accurately recapitulate human pathophysiology during infection and clinical response to antiviral therapeutics are still lacking, which represents a major barrier in drug development. The emergence of human Organs-on-a-Chip that integrated microfluidics with three-dimensional (3D) cell culture, may become the potential solution for this urgent need. Human Organs-on-a-Chip aims to recapitulate human pathophysiology by incorporating tissue-relevant cell types and their microenvironment, such as dynamic fluid flow, mechanical cues, tissue–tissue interfaces, and immune cells to increase the predictive validity of in vitro experimental models. Human Organs-on-a-Chip has a broad range of potential applications in basic biomedical research, preclinical drug development, and personalized medicine. This review focuses on its use in the fields of virology and infectious diseases. We reviewed various types of human Organs-on-a-Chip-based viral infection models and their application in studying viral life cycle, pathogenesis, virus-host interaction, and drug responses to virus- and host-targeted therapies. We conclude by proposing challenges and future research avenues for leveraging this promising technology to prepare for future pandemics.
ABSTRACT
The intestinal tract is a vital organ responsible for digestion and absorption in the human body and plays an essential role in pathogen invasion. Compared with other traditional models, gut-on-a-chip has many unique advantages, and thereby, it can be considered as a novel model for studying intestinal functions and diseases. Based on the chip design, we can replicate the in vivo microenvironment of the intestine and study the effects of individual variables on the experiment. In recent years, it has been used to study several diseases. To better mimic the intestinal microenvironment, the structure and function of gut-on-a-chip are constantly optimised and improved. Owing to the complexity of the disease mechanism, gut-on-a-chip can be used in conjunction with other organ chips. In this review, we summarise the human intestinal structure and function as well as the development and improvement of gut-on-a-chip. Finally, we present and discuss gut-on-a-chip applications in inflammatory bowel disease (IBD), viral infections and phenylketonuria. Further improvement of the simulation and high throughput of gut-on-a-chip and realisation of personalised treatments are the problems that should be solved for gut-on-a-chip as a disease model.