Development of a Gut-on-a-Chip models in a 3D microfluidic platform (OrganoPlate®)

A common bottleneck in any drug development processes is finding an accurate model that will closely mimic disease development and progression. Conventional in-vitro drug screen experiments often rely on two-dimensional (2D) culture systems. These models often provide useful information and insights especially about drug metabolism and penetration. However, at the same time these models have more regularly failed to predict drug targets. Therefore, there is an unmet need for models that will bridge the gap between pre-clinical models and their predictive value throughout the stages of drug development. I described in this thesis the development and characterization of 3D gut-on-chip models developed on high throughput microfluidics platform–OrganoPlate. The in-vitro models were directed towards a disease state by applying downstream signalling molecule of activated immune cells. With this approach I was able to mimic several main characteristics of inflammatory bowel disease (IBD), like loss of barrier integrity and cell activation. After which these diseased gut-on-chip models were used for small scale phenotypic studies. Moreover, the work in this thesis describes four different high throughput models with increasing level of complexity, from simple Caco-2 based in-vitro models to more complex iPSC based ones, to complex tetra-co-culture model where several parts of human physiology are combined to achieve more predictable in-vitro models.