- Stem cells are characterized by their dual ability for self-renewal and differentiation, potentially yielding large numbers of cells that can be used in cell therapy and tissue engineering for repairing devastating diseases. Attaining control over stem cell fate decision in culture is a great challenge since these cells integrate a complex array of "niche" signals, which regulate their fate. Given this, the recent findings that synthetic microenvironments can be designed to gain some level of control over stem cell fate are encouraging. This chapter provides an overview of the current state and knowledge of the design of synthetic microenvironments bio-inspired by the adult stem cell niche. We describe the biomaterials used for reconstituting the niche, highlighting the bioengineering principles used in the process. Such synthetic microenvironments constitute powerful tools for elucidating stem cell regulatory mechanisms that should fuel the development of advanced culture systems with accurate regulation of stem cell fate.