Advancements in in vitro models of traumatic brain injury

Annually, forty to seventy million victims globally are estimated to sustain a traumatic brain injury (TBI). To investigate the link between different types of TBI and neurological deficits, various mechanical loading types associated with trauma to the head and brain have been replicated in animal as well as in vitro cell culture systems. In vitro models have studied how the mechanics of trauma translates to injury mechanisms; discovering potential targets for protection, prevention, and treatment. This article focuses on recent developments made in between 2017 and 2022 and the range of culture systems utilized to focus on specific injury outcomes. The review is structured to delve into the reproduction of mechanical loading used to cause injury including: uniaxial and biaxial stretch, compression, shear, weight drop, scratch, rotational accelera-tion, static pressure, and blast injury. We compare between 2D and 3D injury models, summarize main findings for each model, and list advantages and disadvantages of both ap-proaches. The article also reviews advancements in the use of human induced pluripotent stem cells, new models of repetitive injury, and non-neuronal models of TBI. We identify future di-rections including 1) the need for simplicity in the protocol for hIPSC culture for more widespread use, 2) the need to repli-cate complex mechanical loading in vitro and 3) the need to develop a model using adult neuronal cell sources.