The microenvironments of cells in the human body are known to direct cellular responses, including in healthy versus maladaptive wound healing upon injury. Accordingly, soft materials are being designed inspired by these microenvironments, particularly the extracellular matrix (ECM) that surrounds cells, for probing and controlling cellular responses both in vitro and in vivo, from multidimensional culture models for mechanistic studies to injectable materials for therapeutic delivery. In this talk, I will highlight some of our recent efforts in this arena. For example, through the design of molecularly engineered polymer and peptide building blocks, we have established synthetic ECMs that allow us to probe the response of barrier tissue cells (e.g., epithelial cells, fibroblasts, immune cells) to injury triggered upon the application of light or other stimuli. Integration of physically assembling peptides within such covalently crosslinked networks further imparts designed hierarchical, bioactive nano- and micro-structures and physiologically relevant viscoelasticity. We collaboratively are using bioprinting for the creation of well-defined 3D cultures built upon such materials with high-throughput for the evaluation of therapeutic approaches. Additionally, we are utilizing these molecularly engineered synthetic ECMs in conjunction with flow-based devices for the production of injectable delivery vehicles and cell-based therapies.