Hydrogels have proven useful in a range of human health applications because of their ability to mimic salient tissue properties including high water content, controlled ligand presentation, and soft tissue mechanics. Recent advances in hydrogel design are increasingly moving away from static, monolithic platforms and toward dynamic, interactive, and responsive materials that capture the complexity of native cellular microenvironments in wound healing and tissue regeneration. My group engineers instructive biomaterials to tackle human health challenges include treatment of fibrotic disease and repair of injured tissues. In this talk I will discuss our progress on designing hydrogels as disease models that capture the dynamic mechanical properties of fibrosis as well as using hydrogels mimicking the mechanical environment of developmental niches to repair volumetric muscle loss injuries.