Intestinal Organoid Bioengineering, Disease Modeling, and Drug Discovery

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The intestinal organoid system is a unique ex-vivo representation of the complex and dynamic mammalian intestinal epithelium. Intestinal organoids are threedimensional, crypt-villus structures with a central lumen that can be sourced from adult intestinal stem cells, embryonic stem cells as well as induced pluripotent stem cells. They serve as a bona fide model for not only understanding intestinal biology and development but also for disease modeling, regenerative therapeutics, and drug discovery. Organoids help bridge the gap in existing model systems by incorporating complex, spatial, and biological parameters such as cell-cell interactions, cell-matrix interactions, gut-microbe interactions, and other components of intestinal in-vivo physiology and pathology. In this chapter, we discuss the basic strategies to generate intestinal organoids and how different bioengineering approaches can be used to effectively model both genetic and infectious intestinal diseases to enhance their utility in research and therapeutics.