Stem cells are harbored by distinct and anatomically defined microenvironments. Engineered biomaterials were explored for the ex vivo dissection of exogenous cues that act on stem and progenitor cells. The chapter summarizes biomaterial-based approaches to the spatial and temporal control of factor and ligand presentation. Emphasis is given to the application of glycosaminoglycan-containing hydrogels as a versatile platform for the biomimetic presentation of multiple molecular effectors and for the adjustment of physical constraints.