NSF Award
2403731
It is now recognized that injury to the brain- such as from traumatic brain injury (TBI), is a result of a wide variety of stresses, strains, and strain rates. However, it is not yet known how astrocytes respond to strains across a range of force and strain rate regimes because of challenges associated with access to the tools with the ability to apply small and large forces, at defined distances from astrocytes, in real-time on live cells, with control over strain rates. In this project the investigating team will use controlled, 3D, brain-like cell culture environments and their recently developed ex vivo brain cultures to quantify acute versus chronic response of astrocytes to mechanical perturbation. The project will culminate in defining how astrocytes can activate, permanently or reversibly, in response to low, repeated forces to gain better understanding of how repeated injuries, even at low forces, could put people at risk for brain injuries and long-term disability or death. The fundamental knowledge gained through this research could apply to materials design for better protective gear, monitoring devices for TBI, and better public understanding of forces that could lead to permanent brain damage. Outreach objectives in this project include continued efforts from the Principal Investigators' laboratory to expand engineering research opportunities tailored for high school students that are typically underrepresented in science and engineering.<br/><br/>Astrocytes are one of the most important cell types in the brain. There is increasing interest in studying astrocytes, as emerging studies point to their ability to repair the brain after injury. Understanding how astrocytes repair the brain holds potential towards new class of drugs, preventative measures, or protective gear so that people could fully recover from, or even prevent, brain damage. So far, researchers lacked the tools to effectively grow astrocytes in the laboratory or apply the types of injuries to astrocytes that represent what a person would experience during a brain injury. Injury to the brain, such as from traumatic brain injury, is a result of a wide variety of forces and impacts. Traumatic brain injury is diagnosed in nearly 1.5 million Americans every year, and 5.3 million people live with disabilities caused by traumatic brain injury in the U.S. This project will study how astrocytes respond to injury, in real-time, with live cells, in brain-mimicking environments, and with precise control over the injury forces applied. The research team will use a brain hydrogel environment specifically tailored to grow astrocytes and use a new technique to injure living cells and study their response in real-time. These studies have the potential to transform our understanding of how astrocytes sense and respond to force, across a wide range of strains and stain rates. The research will advance understanding of how brain injury occurs and how it leads to long-term cognitive deficits. This award will support outreach efforts to provide opportunities for female high school students, particularly those from historically excluded groups in STEM, to give them biomechanics and mechanobiology related research opportunities, what is necessary to be a successful female engineer, and how local women have used science and engineering to forge a successful career.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
