Emerging strategies for spatiotemporal control of stem cell fate and morphogenesis

Stem cell differentiation is regulated by the complex interplay of multiple parameters, including adhesive intercellular interactions, cytoskeletal and extracellular matrix remodeling, and gradients of agonists and antagonists that individually and collectively vary as a function of spatial locale and temporal stages of development. Current approaches to direct stem cell differentiation focus on systematically understanding the relative influences of microenvironmental perturbations and simultaneously engineering platforms aimed at recapitulating physicochemical aspects of tissue morphogenesis. This review focuses on novel approaches to control the spatiotemporal dynamics of stem cell signaling and morphogenic remodeling to direct the differentiation of stem cells and develop functional tissues for in vitro screening and regenerative medicine technologies.

► The temporal dynamics of signaling and morphogen delivery alter stem cell fate.
► Biomaterials enable 3D delivery of morphogens and presentation of bioactive ligands.
► Cell signaling can be perturbed via modulation of transport and factor sequestration.
► Perturbation of 3D cell–cell and cell–ECM adhesions induces morphogenic events.