Bioprinted gut-on-a-chip to mimic the intestinal mucosa

Abstract

The search and development of technologies with the ability to replicate the complex characteristics of the human body has increased greatly in recent years. Organ-on-a-chip systems are clear examples, since they allow for the replication of a chosen organ including a representative population of cells and a controlled microenvironment with applied flow conditions, resulting in robust in vitro models that better recapitulate the in vivo tissue conditions, compared to standard 2D or 3D culture methods. The main aim of this final degree project is to develop a bioprinted gut-on-a-chip model to mimic the intestinal mucosa. Firstly, the intestinal mucosa is composed of physical and immune elements and has protective functions. In vitro models that grown monolayers of epithelial cell lines provide a limited representation of the intestinal mucosa. The in vitro model reviewed will mimic the in vivo characteristics of the native tissue including its specific 3D topography, the main cellular components and flow conditions, allowing for a better understanding of its performance. In order to incorporate the intestinal mucosa in our model, a microenvironment must be created in which the cell can live and perform their functions. Hydrogel co-networks based on GelMA and PEGDA have been postulated as the best candidate. The incorporation of microstructured hydrogels, that mimic the three-dimensional structure of the intestine, and the cell environment on the present gut-on-a-chip model, better resemble the physiological conditions thus, having a strong impact on mucosal-related disease modelling and drug testing. The method used to carry out the structuring of the hydrogel has been bioprinting. Specifically, the most commonly used bioprinting methods for the generation of lab-on-chip systems have been analysed and compared, to evidence, the main advantages of the Digital light processing projector-based stereo-lithography printing method, reported in this project...