Materials whose properties can be controlled in time have been utilized in numerous biomedical applications for the past several decades, from controlled drug delivery^1,2  to tissue engineering and regenerative medicine.³  For example, seminal works have demonstrated that hydrolytically degradable moieties, such as anhydrides⁴  or esters,⁵  can be incorporated within the backbone of biomaterials and, upon cleavage and subsequent material erosion, release embedded or encapsulated drugs at a pre-programmed rate.^6,7  These functionalities subsequently were integrated within polymers and polymer networks for the support or delivery of mammalian cells in the replacement or regeneration of tissues.^8,9  More recently, additional classes of degradable units have been utilized, including those responsive to enzymes^10,11  and light,¹²  to tailor the temporal properties of these biomaterials in situ for specific applications. Upon this backdrop, our knowledge has grown rapidly of how the biophysical and biochemical properties of a cell’s microenvironment, particularly the extracellular matrix (ECM), influence cellular functions and fate. Degradable biomaterials have emerged as scaffolds to mimic the dynamic ECM not only for tissue regeneration but also for asking biological questions within an environment closer to that of the native ECM (e.g., three-dimensional, soft, or responsive).^13–16