Synthetic materials for deriving intestinal organoids. (a–d) Effects of hydrogel composition (a), RGD functionalization (b), stiffness (c), and dynamics (d) on the proliferation of stem cells and formation of intestinal organoids. (e) Maturity of intestinal organoids formed from polyethylene glycol (PEG) hydrogel with optimal material properties. (f) Schematic explaining the mechanism of intestinal organoid formation within synthetic, dynamic hydrogels. Higher stiffness and RGD functionalization facilitate initial expansion of stem cells. At a later stage, however, a softer matrix better facilitates the differentiation and maturation of the organoids. Therefore, a dynamic hydrogel system that is stiff at the beginning followed by softening by degradation is desired for intestinal organoid maturation. Images adapted from reference [162
], Nature Publishing Group.