Neural stem cells (NSC) in two regions of the adult mammalian brain continuously generate new neurons throughout human life, and they can potentially be harnessed for neurogeneration. Their behavior is regulated by a complex repertoire of signals that precisely regulate the activation, proliferation, differentiation, and integration of the newborn cells. We have explored whether implantation of engineered biomaterials can stimulate the generation of new neurons in normally quiescent regions of the brain. In this engineered biomaterial microenvironment, new neuron formation was observed in normally non-neurogenic regions of the brain. Additionally, the decreased neurogenesis in the hippocampus of aged rodents was partially rescued toward levels of young animals. We thus demonstrate for the first time de novo neurogenesis stimulated solely by delivery of synthetic biomaterial forms of proteins naturally found within adult neurogenic regions, offering the potential to replace neurons lost in neurodegenerative disease or injury as an alternative to cell implantation.