SBIR-STTR Award

Traumatic brain injury (TBI) is a devastating medical condition that affects a significant number of people in the US with clinical evidence reporting that repeated TBIs, even mild in magnitude, can result in long-term cognitive defects and neuropathology, such as Alzheimer's disease, dementia and chronic traumatic encephalopathy (CTE). However, in mild and especially repeated TBI, the mechanisms for pathology and possible therapeutic strategies are not well-studied, nor are there effective platforms to study these clinically relevant problems. In view of this scientific gap, the broad goal of this proposal is to build upon our existing animal cell-based blood-brain barrier on chip, to engineer and validate a human induced pluripotent cell (iPSC)-derived BBB-chip. The human BBB-chip is intended to be used as: (I) a platform to study the mechanisms for neuropathology following mild and repeated TBI (mrRBI); and (II) a platform for drug safety and efficacy testing.

Traumatic brain injury (TBI) is a significant health issue which affects service members and veterans during times of both peace and war. The high rate of TBI and blast-related concussion events resulting from current combat operations directly impacts the health and safety of individual service members and subsequently the level of unit readiness and troop retention. The impacts of TBI are felt within each branch of service, including the Air Force (~13% from 2000-2020 Q3), and throughout the Department of Defense and the Department of Veterans Affairs health care system. Traumatic brain injury (TBI) is a devastating injury characterized by brain damage caused by external mechanical forces such as a blow or jolt to the head. In the United States, there are an estimated 1.7 million new cases of TBI per year with approximately 70% treated in emergency hospitals. An estimated 10 million people will experience a TBI annually worldwide. In most cases, a TBI is caused by a single impact. However, there are increasing instances of repetitive traumatic insults to the brain, that cause increased vulnerability to downstream pathology. TBI is closely associated with alterations of the blood-brain barrier (BBB). The current gap in research is that there are currently a lack of benchtop models that recapitulate the TBI process for the purpose of studying long-term disease mechanisms, and as a platform for drug development, safety and efficacy testing. Existing brain-chip microphysiological systems do not accurately represent the mechanical aspect that is crucial in study the effects of TBI on brain structure. Our brain-chip, AMBIT (Advanced Microphysiological Brain Injury Technology), is able to provide a TBI-like mechanical insult to study its effects on the BBB. This platform is relevant for drug discovery and testing in the context of TBI-mediated pathologies and other neurotrauma sequelae.