Current challenges and bioengineering aspects in the development of an in vitro model of the human intestinal epithelium

The human intestinal epithelium is a multitasking tissue with different cell types and a complex architecture responsible for molecules/nutrient absorption during food digestion, and working as a physical barrier to the infection of pathogens. Symbiosis with the microbiota regulates metabolic pathways accountable for developing diseases, for example diabetes, obesity, and cancer. Therefore, several in vitro biology-inspired physiological models have been developed to humanize drug tests and study cell behavior. This review uses a design approach to discuss the essential bioengineering parameters required to design an intestinal epithelium microphysiological system (MPS) rationally. Important project parameters are discussed, considering the biological question in hands, hydrogel microenvironment, and relevant engineering criteria to observe and quantify the functionality of this epithelium. Thus, we will focus on recent bioengineering aspects related to the fabrication of the intestine model, such as how the biomaterial (matrix) proprieties (porosity, mechanical force, and curvature) affect the cell behavior and, consequently, the characteristics of in vitro intestinal models. Moreover, the technological approaches used to create a villus-like microarchitecture, lithography, and 3D bioprinting are introduced. Finally, combining villi-crypt microarchitecture with fluid perfusion and hypoxia is discussed to create a more complex intestine-MPS.