Engineering biomaterials to control the neural differentiation of stem cells

•The stem cell niche informs biomaterial design to guide neural differentiation.•Engineering material properties can precisely direct stem cell differentiation.•Emerging technologies are advancing biomaterial-directed stem cell differentiation.•Biomaterial approaches are enabling stem cell therapies and advanced tissue models. Stem cells with the potential for neural differentiation are a promising therapeutic avenue both for treating neurological disease and as a system to advance our fundamental understanding of disease biology in vitro. Precisely controlled extracellular environments that recapitulate critical aspects of embryonic development or the adult stem cell niche are necessary to ensure effective differentiation into the desired cell type. Biomaterials in particular have enabled new avenues for directing stem cell differentiation through the precise presentation of biochemical and biophysical cues. Furthermore, as translation of stem cell technologies necessitates the need for scalable cultures, biomaterials will continue to be valuable tools for guiding stem cell behavior in scalable, complex, three-dimensional cultures. In this review, we highlight the critical signals that guide neurogenesis and how biomaterials can be used to control and direct the neural differentiation of pluripotent and adult stem cells. In addition, we discuss recent new technologies that are further advancing material-based regulation of stem cells. Finally, we highlight the current state of the field and how next-generation biomaterials can enable scalable stem cell culture for cell replacement therapies as well as emerging advanced tissue models for studying tissue morphogenesis and disease pathology.