Successful repair of the injured brain is critical, as traumatic brain injury pathology often involves a secondary cascade of insults that may ultimately lead to worsened neurologic dysfunction. Damage is balanced by the brains attempt to repair itself, the genetic profile of the person, underlying health issues, and age, among other factors. The challenge in using a tissue engineering approach to repair and regeneration is centered at the heterogeneous and complex environment, variables that are difficult to measure and interpret. The brain must be in a state that minimizes rejection, inflammation, immune response, and donor cell death to maximize the intended benefit. Tissue engineering, using a bioactive based scaffold to both counter some of the hostile factors and to chaperone donor cells into the brain, has merit, yet the complexity of transplanting a combination biologic construct to the brain has yet to be successfully transferred to the clinic. Several options, such as cell source, scaffold composition, as well as delivery methods will be discussed.