Tissues in living organisms are subject to dynamic environments orchestrated by multifaceted biochemical reactions and mechanical motions. As such, tissues undergo gradual or sudden remodeling which accompanies changes of mechanical properties, chemical properties, microstructure, and geometry. These transient behaviors of tissues influence biomolecular transports and cellular phenotypic activities. To this end, we have been interested in interrogating the extent to which transient properties of tissues modulate health, disease progression, and therapeutic efficacy of drug or cells. In these efforts, we have been developing hydrogel systems with controlled bioactivity and deformability. We have been also evolving these hydrogel systems to let them undergo shape and structural changes in response to external stimuli. My talk will highlight some significant findings we made by using hydrogel systems that can self-transform and regulate the molecular transports and cellular phenotypes for enhanced treatments of tissue defects.