- Award ID(s):
- 2027367
- PAR ID:
- 10347713
- Date Published:
- Journal Name:
- Journal of Biomechanical Engineering
- Volume:
- 144
- Issue:
- 8
- ISSN:
- 0148-0731
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Traumatic brain injury (TBI), particularly from explosive blasts, is a major cause of casualties in modern military conflicts. Computational models are an important tool in understanding the underlying biomechanics of TBI but are highly dependent on the mechanical properties of soft tissue to produce accurate results. Reported material properties of brain tissue can vary by several orders of magnitude between studies, and no published set of material parameters exists for porcine brain tissue at strain rates relevant to blast. In this work, brain tissue from the brainstem, cerebellum, and cerebrum of freshly euthanized adolescent male Göttingen minipigs was tested in simple shear and unconfined compression at strain rates ranging from quasi-static (QS) to 300 s−1. Brain tissue showed significant strain rate stiffening in both shear and compression. Minimal differences were seen between different regions of the brain. Both hyperelastic and hyper-viscoelastic constitutive models were fit to experimental stress, considering data from either a single loading mode (unidirectional) or two loading modes together (bidirectional). The unidirectional hyper-viscoelastic models with an Ogden hyperelastic representation and a one-term Prony series best captured the response of brain tissue in all regions and rates. The bidirectional models were generally able to capture the response of the tissue in high-rate shear and all compression modes, but not the QS shear. Our constitutive models describe the first set of material parameters for porcine brain tissue relevant to loading modes and rates seen in blast injury.more » « less
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We report the application of stress to biological cells at unprecedented strain (50%), strain rate (180,000 s-1), and throughput (1,800 cells/min) using a high-speed, high actuation force magnetically-driven MEMS chip. This device is uniquely suited to study the effects of impact on large populations of inherently heterogeneous cells, enabling statistical analysis that can elucidate the cell-level ramifications of Traumatic Brain Injury (TBI). To demonstrate the capabilities of the μHammer, we applied TBI-relevant strains and strain rates to human leukemic K562 cells then monitored their proliferation for 9 days. We observed significantly repressed proliferation of the hit cells compared to both the negative and sham controls, indicating success in applying sublethal cellular damage.more » « less
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Abstract The ability to model physiological systems through 3D neural in-vitro systems may enable new treatments for various diseases while lowering the need for challenging animal and human testing. Creating such an environment, and even more impactful, one that mimics human brain tissue under mechanical stimulation, would be extremely useful to study a range of human-specific biological processes and conditions related to brain trauma. One approach is to use human cerebral organoids (hCOs) in-vitro models. hCOs recreate key cytoarchitectural features of the human brain, distinguishing themselves from more traditional 2D cultures and organ-on-a-chip models, as well as in-vivo animal models. Here, we propose a novel approach to emulate mild and moderate traumatic brain injury (TBI) using hCOs that undergo strain rates indicative of TBI. We subjected the hCOs to mild (2 s−1) and moderate (14 s−1) loading conditions, examined the mechanotransduction response, and investigated downstream genomic effects and regulatory pathways. The revealed pathways of note were cell death and metabolic and biosynthetic pathways implicating genes such as CARD9, ENO1, and FOXP3, respectively. Additionally, we show a steeper ascent in calcium signaling as we imposed higher loading conditions on the organoids. The elucidation of neural response to mechanical stimulation in reliable human cerebral organoid models gives insights into a better understanding of TBI in humans.
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