A Standardized Platform for QLED Fabrication and Characterization.

According to the Glasgow Coma Scale (GCS), traumatic brain injury (TBI) is commonly classified by clinical severity, with mild (13–15), moderate (9–12), or severe () [,]. These mild TBIs (mTBIs) can cause a variety of symptoms, such as difficulty focusing, blurred vision, irritability, headaches, sleep problems, and depression, and are difficult to diagnose []. In particular, bTBI is a major cause of death and disability in the United States and is often caused by explosions in war zones [,,]. Unlike blunt force trauma and neurodegenerative diseases, this bTBI occurs when extreme mechanical forces, such as an explosion, are applied to the brain that cause significant disruption of cellular mechanics at the nanoscale [–]. Therefore, bTBI can result in subtle but progressive cellular and molecular changes that have the potential to produce long-term neurological degeneration and dysfunction. While the immediate consequences of bTBI are clinically silent, accumulating evidence suggests that mild trauma from blast exposure can develop post-traumatic stress disorder (PTSD) and chronic traumatic encephalopathy (CTE) [,], even lead to neurological changes, upper respiratory injuries, mild and moderate neurological damage, and lung damages []. Damages from blast injuries impact the central nervous system (CNS) (see ) and as well as the neural progenitor cells of the CNS. Adult hippocampal progenitor cells (AHPCs) are multipotent neural cells in the adult brain. They are capable of proliferation and differentiation into neurons, oligodendrocytes, and astrocytes [,]. Due to their regenerative potential and multipotency, AHPCs are suitable candidates for shockwave exposure experiments aimed at investigating how bTBI [,] alters cellular proliferation and differentiation processes, as well as mechanical properties. (A) Illustration of a blast wave injury to different regions of the brain, i.e., frontal, parietal, temporal, and occipital lobes, and cerebellum and brainstem, showing the widespread nature of the effect of bTBI. (B) Schematic of a shock tube device employed to produce controlled shockwaves. It has a driven section (blue) holding cell cultures (light blue) and a driver section (red), divided by a diaphragm. When activated by pressurizing the driver section with compressed air, the diaphragm bursts and creates the shockwave that propagates through the driven section towards the cells. The cells within the substrates are clamped to the end of the driven section of the shock tube to facilitate shockwave exposure. (C) Schematic showing the transmission of the shockwave through a Petri dish of culture-grown cells. The shockwave is transmitted from top-to-bottom and bottom-to-top, interacting with cells. (D) Illustration of AFM where a cell surface is probed by a cantilever and deflection is measured by a laser-photodetector system to calculate nanoscale alterations. (E) List of parameters assessed by AFM, including cell morphology, surface roughness, deformation, Young’s modulus, viscosity, and retardation time. Functional impacts such as cell viability, differentiation, and proliferation were also measured by PI staining and ICC study to assess the cellular response to bTBI. Along with the extracellular matrix, plasma membrane, transmembrane receptors, cytoskeleton, and nuclear architecture, cell type affects how cells respond to applied forces, enabling neurons and glial cells to respond to their physical surroundings. However, when the forces become too strong, as in TBI, these components may respond differently or fail to function, leading to long-term cell damage and neurodegeneration [,]. Previous research has made noteworthy strides in analyzing neuronal plasma membrane disruption across various injury models and revealed a positive correlation between trauma severity and the degree of membrane disruption []. Stem cells subjected to mechanical trauma experience significant alterations in their ability to proliferate and differentiate, underscoring the sensitivity of these cells to mechanical stimuli []. These mechanical forces play a critical role in modulating stem cell behavior by influencing their proliferation and differentiation []. It was also found that the mechanical environment and stiffness of CNS tissue or biomaterials can affect the differentiation, adhesion, and migration of stem cells. Biomaterial mechanics matching to CNS tissue is important for regenerative medicine because such mechanical cues strongly modulate cellular behavior and the success of therapeutic strategies []. Therefore, it is important to investigate how mechanical forces affect the nanomechanical properties of stem cells following blast trauma, which may contribute to advancements in bTBI diagnostics and treatment.