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In this study, interferon\u2010\u03b3 (IFN\u2010\u03b3) was compared with brain\u2010derived neurotrophic factor (BDNF) and erythropoietin and was shown to be the best single growth factor for inducing neuronal differentiation from adult rat brain\u2010derived NSPCs. Next, IFN\u2010\u03b3 was surface immobilized to a methacrylamide chitosan (MAC) scaffold that was specifically designed to match the modulus of brain tissue and neuronal differentiation of NSPCs was examined <jats:italic>in vitro<\/jats:italic> by immunohistochemistry. Bioactive IFN\u2010\u03b3 was successfully immobilized and quantified by ELISA. Both soluble and immobilized IFN\u2010\u03b3 on MAC surfaces showed dose dependent neuronal differentiation with soluble saturation occurring at 100 ng\/mL and the most effective immobilized IFN\u2010\u03b3 dose at 37.5 ng\/cm<jats:sup>2<\/jats:sup>, where significantly more neurons resulted compared with controls including soluble IFN\u2010\u03b3. \u00a9 2009 Wiley Periodicals, Inc. 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