Infectious diseases remain the subject of intense research. This topic reaches a new era towards the study of host-pathogen interactions mechanisms at the tissue scale.The past few years have hence witnessed the emergence of new methods. Among them, organ-on-chip, which combines biomaterial technology, microfluidic and tissue engineering to recreate the organ physiology is very promising. This review summarises how this technology recapitulates the architecture, the mechanical stimulation and the interface of a tissue and how this particular microenvironment is critical to study host-pathogen interactions.

Blood-circulating devices such as oxygenators have offered life-saving opportunities for advanced cardiovascular and pulmonary failures. However, such systems are limited in the mimicking of the native vascular environment (architecture, mechanical forces, operating flow rates and scaffold compositions). Complications involving thrombosis considerably reduce their implementation time and require intensive anticoagulant treatment. Variations in the hemodynamic forces and fluid-mediated interactions between the different blood components determine the risk of thrombosis and are generally not taken sufficiently into consideration in the design of new blood-circulating devices. In this Review article, we examine the tools and investigations around hemodynamics employed in the development of artificial vascular devices, and especially with advanced microfluidics techniques. Firstly, the architecture of the human vascular system will be discussed, with regards to achieving physiological functions while maintaining antithrombotic conditions for the blood. The aim is to highlight that blood circulation in native vessels is a finely controlled balance between architecture, rheology and mechanical forces, altogether providing valuable biomimetics concepts. Later, we summarize the current numerical and experimental methodologies to assess the risk of thrombogenicity of flow patterns in blood circulating devices. We show that the leveraging of both local hemodynamic analysis and nature-inspired architectures can greatly contribute to the development of predictive models of device thrombogenicity. When integrated in the early phase of the design, such evaluation would pave the way for optimised blood circulating systems with effective thromboresistance performances, long-term implantation prospects and a reduced burden for patients.

Physical forces are essential to biological function, but their impact at the tissue level is not fully understood. The gut is under continuous mechanical stress because of peristalsis. To assess the influence of mechanical cues on enteropathogen invasion, we combine computational imaging with a mechanically active gut-on-a-chip. After infecting the device with either of two microbes, we image their behavior in real time while mapping the mechanical stress within the tissue. This is achieved by reconstructing three-dimensional videos of the ongoing invasion and leveraging on-manifold inverse problems together with viscoelastic rheology. Our results show that peristalsis accelerates the destruction and invasion of intestinal tissue by Entamoeba histolytica and colonization by Shigella flexneri . Local tension facilitates parasite penetration and activates virulence genes in the bacteria. Overall, our work highlights the fundamental role of physical cues during host-pathogen interactions and introduces a framework that opens the door to study mechanobiology on deformable tissues.