The authors present a strategy to create photodegradable poly(ethylene glycol) (PEG)-based hydrogels through rapid polymerization of cytocompatible macromers. These hydrogels can be remotely manipulated in situ to control gel properties, introduce temporal changes, create arbitrarily shaped features, and release pendant functionalities on demand. The photodegradable functionality, derived from a nitrobenzyl ether moiety, allows for real-time manipulation of material properties or chemistry. The hydrogels are synthesized using a base photodegradable acrylic monomer and copolymerized with PEG monoacrylate. Upon irradiation, the hydrogels degrade, releasing modified PEG or poly(acrylate) chains. The degradation rate and extent can be controlled by light intensity and wavelength. The authors demonstrate that this approach can be used to manipulate cell morphology, create channels for cell migration, and modify the biochemical environment to influence chondrogenic differentiation of encapsulated stem cells. This method provides a dynamic platform for studying material regulation of live cell function and has potential applications in drug delivery and tissue engineering.The authors present a strategy to create photodegradable poly(ethylene glycol) (PEG)-based hydrogels through rapid polymerization of cytocompatible macromers. These hydrogels can be remotely manipulated in situ to control gel properties, introduce temporal changes, create arbitrarily shaped features, and release pendant functionalities on demand. The photodegradable functionality, derived from a nitrobenzyl ether moiety, allows for real-time manipulation of material properties or chemistry. The hydrogels are synthesized using a base photodegradable acrylic monomer and copolymerized with PEG monoacrylate. Upon irradiation, the hydrogels degrade, releasing modified PEG or poly(acrylate) chains. The degradation rate and extent can be controlled by light intensity and wavelength. The authors demonstrate that this approach can be used to manipulate cell morphology, create channels for cell migration, and modify the biochemical environment to influence chondrogenic differentiation of encapsulated stem cells. This method provides a dynamic platform for studying material regulation of live cell function and has potential applications in drug delivery and tissue engineering.