Infection-on-Chip: anin vitrohuman vessel to studyNeisseria meningitidiscolonization and vascular damages

Systemic infections leading to sepsis are life-threatening conditions that remain difficult to treat, and the development of innovative therapies is hampered by the limitations of current experimental models. Animal models are constrained by species-specific differences, while 2D cell culture systems fail to capture the complex pathophysiology of infection. To overcome these limitations, we developed a laser photoablation-based, three-dimensional microfluidic model of meningococcal vascular colonization, a human-specific bacterium that causes sepsis and meningitis. We coined our model “Infection-on-Chip”. Laser photoablation-based hydrogel engineering allows the reproduction of vascular networks that are major infection target sites, and this model provides the relevant microenvironment reproducing the physiological endothelial integrity and permeability in vitro . By comparing with human-skin xenograft mouse model, we show that the Infection-on-Chip system not only replicates in vivo key features of the infection, but also enables quantitative assessment with a higher spatio-temporal resolution of bacterial microcolony growth, endothelial cy-toskeleton rearrangement, vascular E-selectin expression, and neutrophil response upon infection. Our device thus provides a robust solution bridging the gap between animal and 2D cellular models, and paving the way for a better understanding of disease progression and the development of innovative therapeutics.