A better understanding of the dynamic physical and biomolecular cues in the stem cell niche has led to a growing interest in the development of material systems for improved 3D culture environments, as well as delivery vehicles to promote cell survival and differentiation. As a result, hydrogels based on both protein components (e.g., collagen and Matrigel) and highly-tunable synthetic chemistries (e.g., PEG) have evolved to address many of these needs. However, as advances in real-time tracking of dynamic cellular functions have emerged, complementary approaches to alter the surrounding extracellular environment in a user-defined and highly-controlled fashion are extremely limited. Such materials systems would have the potential to significantly improve our understanding of how cells receive information from their microenvironment and the role that these dynamic processes may play in biological questions related to their renewal and differentiation. Towards the goal of developing a dynamically tunable scaffold, we recently reported an approach for in situ hydrogel property manipulation with light, allowing intimate control of a cell’s microenvironment in both time and space. These photoactive hydrogels afford unique user-defined manipulation of the biochemical and biomechanical nature of the extracellular microenvironment. This talk will present several examples where user-triggered changes in the material environment can be used to both better understand and direct the function of bone marrow derived mesenchymal stem cells.