Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide, presenting a significant challenge due to the lack of effective therapies. Neural stem cells (NSCs) have shown promising potential in preclinical studies as a therapy for TBI. However, their application is limited by challenges related to poor survival and integration within the injured brain. This study investigated the effect of a novel nano-scaffold containing stromal cell-derived factor 1 (SDF-1) on NSC behavior and synaptogenesis after TBI. Using an innovative design, we successfully fabricated a nano-scaffold with Young's modulus of approximately 3.21 kPa, which aligns closely with the mechanical properties exhibited by neural tissue. This achievement marks the first time such a scaffold has been created and has promising implications for its potential use in neural tissue engineering applications. Our findings demonstrate that the nano-scaffold enhances NSC proliferation, migration, and differentiation capacity in vitro. Moreover, when transplanted into the injured brain, the nano-scaffold promotes the survival and integration of NSCs, leading to increased synaptogenesis and functional recovery. These findings suggest that using the novel nano-scaffold containing SDF-1 could provide a promising approach to treating TBI by improving NSC behavior and promoting synaptogenesis.