Chitosan is a natural biomaterial (distributed widely in insects, invertebrates, fungi and yeasts) that mimics native polysaccharides such as hyaluronan, and has many useful biological properties such as bioresorbable degradation products, hydrophilicity, biocompatibility, and cellular binding capabilities that make chitosan well suited as a tissue engineering scaffolding material. I have selected chitosan as the basic substrate to support neural stem cell 3-D differentiation and proliferation; both in vitro and in vivo studies have been completed. The main objective was to develop a preferred method to encourage neural stem/progenitor cell (NSPC) differentiation into desired cell types (neurons, oligodendrocytes and astrocytes). All studies focused on testing how different 3-D biomaterial-growth factor systems guide NSPC differentiation, in order to form tissue engineered constructs. This knowledge is invaluable for future treatments targeted for regenerating the injured or damaged center nervous system. The overall hypothesis of this study was that an appropriate 3-D scaffold with suitable biochemical factors can be fabricated, and this scaffold can encourage NSPCs to differentiate into specific and desired cell phenotypes for tissue engineering application. To test these hypotheses, three specific aims were performed: (1) Tuning of an appropriate 3-D biomaterial scaffold for NSPC differentiation; (2) selection of growth factors and immobilization of growth factors to guide NSPC differentiation in vivo; (3) examining implantation of tissue engineered grafts after spinal cord hemisection.