A bioengineering platform recapitulating the intestinal environment for intestinal epithelium and gut microbiota in vitro models

The human gut is a complex ecosystem and its recapitulation in vitro remains challenging. State-of-the-art systems fail to fully reproduce the kinematics of gut motility, resulting in suboptimal models of the intestinal function. This PhD research aims at overcoming this bottleneck through the design, development, and validation of a novel millifluidic bioengineering platform that recapitulates key features of the intestinal environment, including physiological peristalsis and fluidic shear stress, for relevant gut microbiota or intestinal epithelium in vitro models. The system features a pneumatic-driven peristalsis system, a flexible culture chamber, a custom-designed scaffold supporting the in vitro cultures, the possibility to monitor key environmental parameters, and the ability to generate and maintain hypoxic conditions. The system was then validated. Specifically, its ability to generate biomimetic models of the human gut microbiota under a combined flow-peristalsis stimulation and establish a relevant intestinal epithelium model for in vitro applications was demonstrated. Additionally, preliminary indirect co-culture tests assessed the ability of microbial secretomes to support epithelial viability and metabolic activity. Collectively, this work contributes to the research field by providing a versatile, modular, millifluidic bioreactor establishing both microbial and epithelial biomimetic in vitro models through the application of relevant biomechanical stimuli.