UC San Diego

Traumatic brain injury (TBI) is a common clinical condition in which the brain is subject to a mechanical injury. This results in short- and long-term clinical symptoms and also increases the risk for future neurodegeneration. Previous studies trying to link TBI with its long-term outcomes have only been performed on animal or culture cell models, but very few studies have been performed on 3D human cellular models. These limitations are major barriers for current translation of preclinical science to clinical implementation. Recent studies suggest that 3D brain organoids may be a useful model to study links between TBI and downstream adverse effects. Previous experiments suggest that injuring organoids one at a time through the use of a modified mouse CCI impactor is tedious and creates high variability. In this thesis study, a novel brain organoid impact device was designed, manufactured, and tested to effectively model TBI in a human system. Through phantom organoid and human organoid testing, the impact device demonstrated a more simple, accurate, and efficient model to injure brain organoids, compared to its predecessors. The device allows for simultaneous injury of multiple organoids, consistent and controlled deformation of organoids, and the ability to vary impact force and velocity, based on gravity and the defined compression of a spring. This study represents a dramatic improvement over previous TBI organoid models, and will enable us to better understand downstream effects TBI towards improve translation between preclinical and clinical models. It is anticipated that this device will support a variety of experiments to evaluate TBI related diagnostics, therapeutics, biomarkers, and mechanisms of disease progression.