A) Photoreversible patterning of the protein vitronectin within well-defined hydrogel-based matrices controls encapsulated MSC differentiation. PEG-based hydrogels were formed by strain promoted azide-alkyne cycloaddition and B) patterned with vitronectin (dashed line regions), which promoted osteogenic differentiation (green stain indicates cells expressing the osteogenic marker osteocalcin). The regions of the hydrogel with no vitronectin exhibit limited MSC interaction with the matrix (e.g., rounded cell morphology) and limited osteogenic differentiation (no green), where all of the MSCs were stained with CellTracker Red. Adapted from DeForest and Tirrell with permission from Nature Publishing Group [62]. C) MMP-degradable HA hydrogels that allow MSC spreading and traction force generation (-) promote osteogenic differentiation. After secondary crosslinking at day 7 (D7 UV), spread cells are unable to degrade the matrix, affecting their ability to generate traction forces, and D) promoting differentiation into adipocytes instead of osteoblasts. Adapted from Burdick and coworkers with permission from Nature Publishing Group [31].