Reconstruction and regeneration of the central nervous system (CNS) following injury is a formidable task. However, cell replacement with transplanted neural progenitor cells (NPC) is a promising technique that has resulted in various levels of functional recovery in animals that had experienced an experimental injury of the brain or spinal cord. Unfortunately, CNS injury often leads to significant tissue damage and loss, limiting the survival and integration of transplanted NPC. In response, researchers have developed many biomaterial substrates that have been used to culture, transplant, and influence the differentiation and integration of transplanted NPC. Biomaterial scaffolds are a three-dimensional lattice that can be engineered to support NPC in vitro as well as serving as a temporary extracellular matrix (ECM) after transplantation. Scaffold modification with bioactive components, such as proteins, adhesive peptide sequences, and growth factors, allow researchers to modulate NPC responses as well as the local environment of the transplantation site. Biomimetic approaches also can include materials that recapitulate the structural dimensions of the ECM, namely self-assembling nanofibers. These materials can be useful for altering the tissue microenvironment by reducing inflammation and glial scarring, which may further enhance NPC survival and integration into functional neural circuitry. This review describes various biomaterial constructs, with a focus on biomimetic systems that have been used in modulating NPC behavior in culture and/or in transplanting NPC to the CNS.