Using our 3D in vitro brain models, we are able to mimic traumatic brain injury (TBI) such as concussion and contusion injuries and study the resultant cellular and tissue response to better understand which molecular mechanisms and biomarkers are activated. For the contusion model, a controlled cortical impact (CCI) method is used to inflict an injury with cytokine expression, as well as cell viability, activity, and cytotoxicity, assessed post-injury. This is in parallel with INSciDE collaborators (Whalen lab, MGH) who have developed in vivo mouse models of concussive TBI that induce long term cognitive deficits and neurodegeneration (>6 mos) in the absence of acute cell death, edema, blood-brain barrier damage, and gross structural brain injury. As such our 3D in vitro brain models have been developed using primary mouse cortical neurons, though human-derived cells may be used as well. Glial cells including astrocytes may be incorporated to increase the cellular complexity and physiological relevance of the models.