Synthetic ECMs with tunable biophysical and biochemical properties. (A) Schematic of cell-encapsulating hydrogel. Adhesive ligand-functionalized 4-arm PEG (PEG-4MAL) is reacted with a thiol-flanked protease-degradable peptide in the presence of cells to form a hydrogel network. Hydrogels support epithelial morphogenesis program. Bar, 50 µm. (B) Tethered RGD density (mean ± SEM) in hydrogel as a function of input RGD concentration. Linear regression: y = 1.02x + 0.55, P < 0.0001. (C) Relationship between polymer density (wt%) and hydrogel equilibrium mass swelling ratio (Qm; left axis, mean ± SEM) and elastic modulus (right axis, mean ± SEM). (D) Cartoon illustrating independent control of polymer density, adhesive ligand density, and cross-link density/network degradation rate in PEG-4MAL hydrogels.