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This lecture explores the engineering of functional intestinal stem cell niches, focusing on the combination of stem cell biology and engineering to grow mini-intestines in a chemically defined 3D matrix. It delves into the key signals of the intestinal stem cell niche, the formation of intestinal organoids, and the influence of matrix mechanics on stem cell self-renewal and differentiation. The role of matrix stiffness, YAP activity, and spatial confinement in organoid development is discussed, along with the importance of a suitable microenvironment for proper self-organization. The lecture also covers the use of biomicrofluidic chips, scaffold-guided morphogenesis, and the modeling of tissue-tissue interactions to study tissue and disease biology.