Virginia Research Day 2022

Graduate Student Research Biomedical

02 3D In Vitro Hydrogel System For Blast Induced TBI Modeling To Study Oligodendrocyte Precursor Cell Response

Ryosuke Yokosawa 1 ; Rachel A. Mazur 2 ; Kyle J. Lampe 2 ; Pamela J. VandeVord 1 Corresponding author: ryokosawa@vt.edu

1 Virginia Tech 2 University of Virginia

on cell death. As future studies, we are aiming to observe if the blast exposure affects the morphology of OPCs as well as the maturation process of the OPCs.

3D hydrogel in vitro models. [4] Hydrogels have been a major application to create a 3D cell based in vitro model because of its properties that mimics the physiologically relevant cell culture environment. Our team has been using the hyaluronic acid (HA) hydrogel system [5] to study morphological and molecular responses of the oligodendrocyte precursor cells (OPCs). Our team has implemented the hydrogel system to the blast wave generator in order to conduct the blast experiment. [Figure 1] The first step of this study is to investigate if the blast pressure exposure affects viability of the OPCs. The next step is to investigate if the blast pressure exposure affects differentiation of the OPCs in response to the blast exposure. Preliminary results demonstrate the viability of OPCs after blast exposure; however, the blast pressure does not directly have an acute effect

Traumatic brain injury (TBI) is one of the most significant public health issues in the United States. TBI related patient visits are approximately 1 million per year in the 1990s and 2000s. [1] Blast induced TBI (bTBI) is one of the TBI categories that is caused by explosive blast exposures. bTBI is often diagnosed within a military population, and the basic injury mechanism is known to be a pressure propagation through a brain tissue. [2] The consequences of bTBI are motor deficits, headaches, and cognitive issues. bTBI has been studied commonly in in vivo rodent models. These studies demonstrate cognitive and motor deficits by using behavior, cellular and molecular assays before and after the blast pressure exposure. [3] Glial cells such as astrocytes, microglia, and oligodendrocytes have been investigated and modeled with the

Figure 1 Cell blasting system adapted by the 3D hydrogel system encapsulating the oligodendrocyte precursor cells

[1] Coronado et al. Trends in Traumatic Brain Injury in the U.S. and the public health response: 1995–2009, Journal of Safety Research, Volume 48, February 2014, Pages 117 [2] Phipps et al. (2020) Characteristics and Impact of U.S. Military Blast-Related Mild Traumatic Brain Injury: A Systematic Review. Front. Neurol. 11:559318. doi: 10.3389/fneur.2020.559318 [3] Dickerson et al. (2020) Glial Activation in the Thalamus Contributes to Vestibulomotor Deficits Following Blast-Induced Neurotrauma. Front. Neurol. 11:618. doi: 10.3389/fneur.2020.00618

[4] Hlavac et al. Mechano-stimulation initiated by extracellular adhesion and cationic conductance pathways influence astrocyte activation, Neuroscience Letters 739 (2020) 135405. [5] Unal et al. Biomacromolecules 2020 21 (12), 4962-4971 DOI: 10.1021/acs. biomac.0c01164

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