Extracellular matrix (ECM) influences cell differentiation through its structural and biochemical prop-erties. In nervous system, neuronal behavior is influenced by these ECMs structures which are present in a meshwork, fibrous, or tubular forms encompassing specific molecular compositions. In addition to contact guidance, ECM composition and structures also exert its effect on neuronal differentiation. This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system, and their impact on neural regeneration and neuronal differentiation. Using topographies, stem cells have been differentiated to neurons. Further, focussing on engineered biomimicking topogra-phies, we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation.