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This lecture explores the influence of the microenvironment on cellular behavior, focusing on the creation of artificial extracellular matrices (ECMs) for tissue engineering. Topics include the use of dynamic chemistries in hydrogels, cell-secreted matrix remodeling, synthetic alternatives to Matrigel, and the design of ECM-mimicking biomaterials. The lecture also discusses the challenges in replacing Matrigel with synthetic scaffolds for engineered organoids, the role of synthetic adhesion peptides like RGD, and the development of artificial intestinal organoid matrices. The complexity of recreating the spatio-temporal network of the native ECM in the lab is highlighted.