Scholarly Works, Biomedical Engineering

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Evaluating Chronic Sex-Specific Changes in Glutamatergic Signaling Markers Following Traumatic Brain Injury
Talty, Caiti-Erin; Wypyski, Madison S.; Murphy, Susan F.; VandeVord, Pamela J. (MDPI, 2026-03-14)
Traumatic brain injury (TBI) can lead to persistent adverse outcomes, including cognitive and emotional dysfunction, with recent estimates indicating that up to 50% of individuals with mild TBI experience long-term symptoms. Growing evidence suggests that biological sex influences TBI outcomes and recovery trajectories; however, the molecular underpinnings driving these sex-specific differences remain poorly understood. In this study, a preclinical TBI model was used to directly compare chronic glutamatergic alterations in adult male and female Sprague Dawley rats. To define frontocortical molecular signatures associated with sex-specific glutamatergic dysfunction, proteomic analyses were conducted. Proteomic data revealed dysregulation of key pathways, cellular processes, and molecular regulators involved in excitatory signaling and synaptic function in both sexes. Biomarker profiling identified a single common biomarker between males and females, along with multiple biomarkers unique to each sex. Furthermore, two key brain regions highly susceptible to TBI, the prefrontal cortex and hippocampal subregions, were examined for chronic alterations in key glutamatergic signaling proteins, including N-methyl-D-aspartate (NMDA) receptors and the excitatory synaptic marker postsynaptic density protein 95 (PSD95). Immunofluorescence analyses revealed both sex- and region-specific alterations in the expression of NMDA receptor subunits, as well as in PSD95. Notably, many of these changes were concentrated within the hippocampal subregions, suggesting long-term dysregulation of hippocampal glutamatergic circuitry following injury. Together, these findings indicate the emergence of chronic sex-specific pathophysiology in glutamate signaling after TBI and highlight the importance of incorporating sex as a biological variable in the development of precision medicine-based therapeutic strategies for TBI.
Assessments with Double Simultaneous Tactile Stimulation following Stroke: A Scoping Review Protocol
Paul, Arco; Holstege, Noah; Johnson, Caroline; Shalaby, Mei; Yau, Jeffrey; Chui, Kevin; Parcetich, Kevin; Comer, C. Cozette; Gurari, Netta (2026-03-24)
Intact somatosensory perception is essential to interact with our surrounding environment, including when performing basic daily tasks and learning skilled movements. Successful execution of voluntary movements depends on accurately processing and perceiving the incoming somatosensory information through integrated sensorimotor pathways. Somatosensory impairments following stroke are relatively common, affecting upwards of 85% of survivors living with stroke. Loss of tactile perception is among the most frequent occurring of the somatosensory impairments, impacting approximately 50% of these individuals in the USA. Common tactile impairments include hypoesthesia (reduced ability to feel touch), dysesthesia (abnormal tactile perception), and impaired two-point discrimination (reduced ability to discriminate between two nearby locations of touch). These impairments are often assessed using unilateral tactile stimulation on the more severely-affected (paretic) side, and, accordingly, do not capture more complex tactile impairments that can arise during bilateral interactions. One such impairment is tactile extinction (TE), a condition in which individuals can detect unilateral tactile stimuli on either side of the body but fail to perceive the same tactile stimuli on the paretic side when both sides are stimulated simultaneously. Most activities of daily living rely on coordinating touching and feeling of objects and using both upper extremities to manipulate them in a dynamic manner, such that both arms are stimulated. Tactile dysfunction that suppresses perception during such bilateral tasks can disrupt motor performance in daily activities and recovery. Therefore, understanding the nature of tactile dysfunction during bilateral tasks following stroke is valuable when considering how to effectively assess and, in turn, treat individuals. In this scoping review, we will explore approaches to assess tactile perceptual dysfunction during bilateral interactions post-stroke. Our aim is to summarize the current status of double simultaneous tactile stimulation approaches used for assessing tactile dysfunction. By considering the design of these approaches, we will identify need for further research, such as additional methods for assessment and implications of existing methods for interpreting why bilateral tactile dysfunction arises following stroke.
Transcriptional Adaptations to Muscle Loading in a Murine Model of Achilles Tendinopathy
Easley, Dylan C.; Menarim, Bruno C.; Grange, Robert W.; Brolinson, P. Gunnar; Wang, Vincent M.; Dahlgren, Linda A. (Wiley, 2026-02-01)
Achilles tendinopathy limits mobility and decreases quality of life. Physical therapy (eccentric muscle loading) improves tendon function; however, the underlying mechanisms are unknown. This study investigated the effect of load magnitude and treatment duration in a mouse Achilles tendinopathy model. We hypothesized that loading would upregulate signaling and metabolic transcriptional networks associated with improved tendon healing. Mice were randomly assigned to muscle loading groups (50 or 100% body weight (BW)) or age-matched injured/untreated (IU) and naïve control groups. Following induction of Achilles tendinopathy via paired TGFB-β1 injections, loading was performed for 1, 2, or 4 weeks, mice euthanized, and Achilles tendons harvested for transcriptomics. The exercised groups exhibited relatively converging transcriptional patterns at 4 weeks, while the IU group was tightly associated with the naïve group over time, and diverging from both exercised groups at 2 and 4 weeks. Two weeks of exercise at either 50 or 100% BW load resulted in uniquely expressed gene networks not present in unexercised controls. Comparative assessment of the expression profile and functional annotation of networks across groups revealed that exercise differentially affected the innate immune response, sensory innervation and collagen biosynthesis during tendon repair. Ingenuity Pathway Analysis further suggests that 50% BW loading is associated with a shorter pro-inflammatory response and early matrix deposition in healing tendons compared to 100% BW loading. The transcriptional alterations seen in response to 50% BW eccentric muscle loading support the benefits of controlled loading exercises when treating Achilles tendinopathy.
A Feasibility Study of Real-Time FMRI with Neurofeedback of Motor Performance in Cerebellar Ataxia
Berenbaum, Joshua G.; Marvel, Cherie L.; Lisinski, Jonathan M.; Soldate, Jeffrey S.; Morgan, Owen P.; Kucharski, Ashley N.; Lutzel, Luca P.; Ecker, Jonathan A.; Rice, Laura C.; Mistri, Amy; Nadkarni, Prianca A.; Rosenthal, Liana S.; LaConte, Stephen M. (MDPI, 2026-01-23)
Background/Objectives: Neurodegenerative cerebellar ataxia (CA) is a movement disorder caused by progressive cell death in the cerebellum. Motor imagery represents a potential therapeutic tool to improve motor function by “exercising” brain regions associated with movement, without the need for overt activity. This study assessed the feasibility of combining motor imagery with real-time functional magnetic resonance imaging neurofeedback (rt-fMRI-NF) to improve motor function in CA. Methods: During finger tapping conditions, 16 participants with CA pushed a button at the same frequency in time with cross flashing at 1 Hz or 4 Hz, and this information was used to train the model. During motor imagery, participants imagined finger tapping while undergoing rt-fMRI-NF with visual feedback, steering them toward activating their motor circuit. Afterwards, they completed finger tapping again. FMRI analysis compared successful motor imagery trials versus all other imagery events. Brain activity on successful trials was covaried with pre–post rt-fMRI-NF tapping improvement scores. Results: Tapping was more accurate at 1 Hz than 4 Hz, and larger tapping error rates correlated with greater movement impairments. While not significant at the group level, 9 of the 16 participants improved tapping accuracy following rt-fMRI-NF. The size of motor improvements correlated with successful motor imagery activity at 1 Hz in the frontal lobe, insula, parietal lobe, basal ganglia, and cerebellum. Motor improvements were not associated with neurological impairment severity, mood, cognition, or imagery vividness. Conclusions: Feasibility was demonstrated for motor imagery therapy with neurofeedback to potentially improve fine motor precision in people with CA. Brain regions relevant to this process may be considered for targets of non-invasive therapeutic interventions.
Confinement in fibrous environments positions and orients mitotic spindles
Sarkar, Apurba; Jana, Aniket; Agashe, Atharva; Wang, Ji; Kapania, Rakesh; Gov, Nir S.; DeLuca, Jennifer G.; Paul, Raja; Nain, Amrinder (Oxford University Press, 2025-07)
Accurate positioning of the mitotic spindle within the rounded cell body is critical to physiological maintenance. Mitotic cells encounter confinement from neighboring cells or the extracellular matrix (ECM), which can cause rotation of mitotic spindles and tilting of the metaphase plate (MP). To understand the effect of confinement on mitosis by fibers (ECM confinement), we use flexible ECM-mimicking nanofibers that allow natural rounding of the cell body while confining it to differing levels. Rounded mitotic bodies are anchored in place by actin retraction fibers (RFs) originating from adhesions on fibers. We discover that the extent of confinement influences RF organization in 3D, forming triangular and band-like patterns on the cell cortex under low and high confinement, respectively. Our mechanistic analysis reveals that the patterning of RFs on the cell cortex is the primary driver of the MP rotation. A stochastic Monte Carlo simulation of the centrosome, chromosome, membrane interactions, and 3D arrangement of RFs recovers MP tilting trends observed experimentally. Under high ECM confinement, the fibers can mechanically pinch the cortex, causing the MP to have localized deformations at contact sites with fibers. Interestingly, high ECM confinement leads to low and high MP tilts, which we mechanistically show to depend upon the extent of cortical deformation, RF patterning, and MP position. We identify that cortical deformation and RFs work in tandem to limit MP tilt, while asymmetric positioning of MP leads to high tilts. Overall, we provide fundamental insights into how mitosis may proceed in ECM-confining microenvironments in vivo.
Mechanical cues guide the formation and patterning of 3D spheroids in fibrous environments
Sharma, Sharan; Agashe, Atharva; Hill, Jennifer C.; Ganguly, Keya; Sharma, Puja; Richards, Tara D.; Huang, Weijian; Kaczorowski, David J.; Sanchez, Pablo G.; Kapania, Rakesh; Phillippi, Julie A.; Nain, Amrinder (Oxford University Press, 2025-09)
Multicellular spheroids have shown great promise in 3D biology. Many techniques exist to form spheroids, but how cells take mechanical advantage of native fibrous extracellular matrix (ECM) to form spheroids remains unknown. Here, we identify the role of fiber diameter, architecture, and cell contractility on spheroids’ spontaneous formation and growth in ECM-mimicking fiber networks. We show that matrix deformability revealed through force measurements on aligned fiber networks promotes spheroid formation independent of fiber diameter. At the same time, larger-diameter crosshatched networks of low deformability abrogate spheroid formation. Thus, designing fiber networks of varying diameters and architectures allows spatial patterning of spheroids and monolayers simultaneously. Forces quantified during spheroid formation revealed the contractile role of Rho-associated protein kinase in spheroid formation and maintenance. Interestingly, we observed spheroid–spheroid and multiple spheroid mergers initiated by cell exchanges to form cellular bridges connecting the two spheroids. Unexpectedly, we found large pericyte spheroids contract rhythmically. Transcriptomic analysis revealed striking changes in cell–cell, cell–matrix, and mechanosensing gene expression profiles concordant with spheroid assembly on fiber networks. Overall, we ascertained that contractility and network deformability work together to spontaneously form and pattern 3D spheroids, potentially connecting in vivo matrix biology with developmental, disease, and regenerative biology.
New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?
Williams, Zachary J.; Payne, Laura Beth; Wu, Xiaobo; Gourdie, Robert G. (Elsevier, 2025-01)
Voltage-gated sodium channels (VGSCs) are transmembrane protein complexes that are vital to the generation and propagation of action potentials in nerve and muscle fibers. The canonical VGSC is generally conceived as a heterotrimeric complex formed by 2 classes of membrane-spanning subunit: an α-subunit (pore forming) and 2 β-subunits (non–pore forming). NaV1.5 is the main sodium channel α-subunit of mammalian ventricle, with lower amounts of other α-subunits, including NaV1.6, being present. There are 4 β-subunits (β1–β4) encoded by 4 genes (SCN1B–SCN4B), each of which is expressed in cardiac tissues. Recent studies suggest that in addition to assignments in channel gating and trafficking, products of Scn1b may have novel roles in conduction of action potential in the heart and intracellular signaling. This includes evidence that the β-subunit extracellular amino-terminal domain facilitates adhesive interactions in intercalated discs and that its carboxyl-terminal region is a substrate for a regulated intramembrane proteolysis (RIP) signaling pathway, with a carboxyl-terminal peptide generated by β1 RIP trafficked to the nucleus and altering transcription of various genes, including NaV1.5. In addition to β1, the Scn1b gene encodes for an alternative splice variant, β1B, which contains an identical extracellular adhesion domain to β1 but has a unique carboxyl-terminus. Although β1B is generally understood to be a secreted variant, evidence indicates that when co-expressed with NaV1.5, it is maintained at the cell membrane, suggesting potential unique roles for this understudied protein. In this review, we focus on what is known of the 2 β-subunit variants encoded by Scn1b in heart, with particular focus on recent findings and the questions raised by this new information. We also explore data that indicate β1 and β1B may be attractive targets for novel antiarrhythmic therapeutics.
Gap junctional and ephaptic coupling in cardiac electrical propagation: homocellular and heterocellular perspectives
Wu, Xiaobo; Payne, Laura Beth; Gourdie, Robert G. (Wiley, 2025-05-31)
Electrical communication in the heart is crucial for maintaining normal cardiac function. Traditionally, gap junctional coupling between cardiomyocytes has been accepted as the primary mechanism governing electrical propagation in the heart. However, numerous studies have demonstrated that gap junctions are also present between different cell types in heterocellular structures and disruption of such gap junctional coupling can be associated with cardiac dysfunction. In addition to gap junctional coupling, ephaptic coupling has been proposed as another mechanism for electrical communication between cardiomyocytes. Reducing ephaptic coupling has been shown to have negative impacts on cardiac conduction. While the existence of ephaptic coupling between different types of cardiac cell is under investigation, a recent study suggests that ephaptic coupling at heterocellular contacts between cardiomyocytes and fibroblasts may provide a proarrhythmic substrate in cardiac disease. In this review, we examine the current literature on electrical communication in the heart, including gap junctional and ephaptic coupling in homocellular and heterocellular contexts. Further, we offer a perspective on gaps in knowledge and opportunities for further advancing our understanding of electrical coupling mechanisms in action potential propagation in the heart. (Figure presented.).
Comparison of conjunctival pedicle flap to corneal fixation strength achieved by Tisseel® fibrin glue, ethyl cyanoacrylate adhesive, ReSure® hydrogel sealant, and conventional suturing with 8-0 VICRYL® ophthalmic suture
VerHulst, Elodie M.; Galarza, Roxanne M. Rodriguez; Herring, Ian P.; Ramos, Renata Velloso; Kemper, Andrew R. (Wiley, 2025-03-01)
Objective To determine and compare the fixation strength of conjunctival pedicle flaps to cornea achieved via conventional ophthalmic suture and three different adhesive compounds. Animals Studied Ex vivo porcine globes. Procedures Following a 6 mm wide 500-micron-restricted depth lamellar keratectomy, conjunctival pedicle flaps were secured to the keratectomy site with either 8-0 VICRYL (R) suture or one of three adhesive products, including Tisseel (R) bioadhesive, ReSure (R) synthetic adhesive, or ethyl cyanoacrylate adhesive (n = 10 per surgical group). Adhesive application protocol varied by product based upon adhesive biocompatibility. Corneoconjunctival tissues were then harvested, clamped in a tensile testing device, and loaded at a rate of 1 mm/s under video surveillance until the point of failure. Peak load was determined for each test and used to compare fixation strength between samples. Results Forty conjunctival flaps were performed, with 6 omitted from evaluation due to dehiscence prior to tensile testing. Of the 34 flaps analyzed, 10 were secured with suture, 10 with cyanoacrylate, 8 with ReSure (R), and 6 with Tisseel (R). Flaps secured with suture withstood significantly higher applied tensile force compared with cyanoacrylate (p = .02474), ReSure (R) (p = .00000), and Tisseel (R) (p = .00002). Flaps secured with cyanoacrylate withstood significantly greater force than those secured with ReSure (R) and Tisseel (R) (p = .01194 and 0.01798, respectively). There was no significant difference in fixation strength between ReSure (R) and Tisseel (R) glue (p = .95675). Conclusions Conjunctival pedicle flap fixation using 8-0 VICRYL (R) suture fixation was able to withstand significantly greater maximum tensile force compared to ReSure (R), Tisseel (R), or cyanoacrylate adhesives. Fixation strength achieved with cyanoacrylate adhesive was significantly greater than that achieved with ReSure (R) or Tisseel (R).
Characterizing Natural Frequencies of the Hybrid III and NOCSAE Headforms
Dingelstedt, Kristin J.; Rowson, Steven (Springer, 2024-10-01)
The vibrational characteristics of the Hybrid III and NOCSAE headforms are not well understood. It is hypothesized that they may perform differently in certain loading environments due to their structural differences; their frequency responses may differ depending on the impact characteristics. Short-duration impacts excite a wider range of headform frequencies than longer-duration (padded) impacts. While headforms generally perform similarly during padded head impacts where resonant frequencies are avoided, excitation of resonant frequencies during short-duration impacts can result in differences in kinematic measurements between headforms for the matched impacts. This study aimed to identify the natural frequencies of each headform through experimental modal analysis techniques. An impulse hammer was used to excite various locations on both the Hybrid III and NOCSAE headforms. The resulting frequency response functions were analyzed to determine the first natural frequencies. The average first natural frequency of the NOCSAE headform was 812 Hz. The Hybrid III headform did not exhibit any natural frequencies below 1000 Hz. Comparisons of our results with previous studies of the human head suggest that the NOCSAE headform's vibrational response aligns more closely with that of the human head, as it exhibits lower natural frequencies. This insight is particularly relevant for assessing head injury risk in short-duration impact scenarios, where resonant frequencies can influence the injury outcome.
Bilayer surrogate brain response under various blast loading conditions
Norris, Carly; Arnold, B.; Wilkes, Jessica M.; Squibb, Carson; Nelson, Allison J.; Schwenker, Hannah; Mesisca, Jenna K.; Vossenberg, A.; Vandevord, Pamela J. (Springer, 2024-08-01)
Variations in the experimental constraints applied within blast simulations can result in dramatically different measured biomechanical responses. Ultimately, this limits the comparison of data between research groups and leads to further inquisitions about the "correct" biomechanics experienced in blast environments. A novel bilayer surrogate brain was exposed to blast waves generated from advanced blast simulators (ABSs) where detonation source, boundary conditions, and ABS geometry were varied. The surrogate was comprised of Sylgard 527 (1:1) as a gray matter simulant and Sylgard 527 (1:1.2) as a white matter simulant. The intracranial pressure response of this surrogate brain was measured in the frontal region under primary blast loading while suspended in a polyurethane spherical shell with 5 mm thickness and filled with water to represent the cerebrospinal fluid. Outcomes of this work discuss considerations for future experimental designs and aim to address sources of variability confounding interpretation of biomechanical responses.
High-Frequency Irreversible Electroporation Alters Proteomic Profiles and Tropism of Small Tumor-Derived Extracellular Vesicles to Promote Immune Cell Infiltration
Murphy, Kelsey R.; Aycock, Kenneth N.; Marsh, Spencer; Yang, Liping; Hinckley, Jonathan; Selmek, Aubrie; Gourdie, Robert G.; Bracha, Shay; Davalos, Rafael V.; Rossmeisl, John H.; Dervisis, Nikolaos G. (MDPI, 2025-11-13)
High-frequency irreversible electroporation (H-FIRE) is a nonthermal tumor ablation technique that disrupts the blood–brain barrier (BBB) in a focal and reversible manner. However, the mechanisms underlying this disruption remain poorly understood, particularly the role of small tumor-derived extracellular vesicles (sTDEVs) released from ablated tumor cells. In this study, we investigate the proteomic and functional alterations of sTDEVs released from F98 glioma and LL/2 Lewis lung carcinoma cells following H-FIRE ablation. Mass spectrometry analysis revealed 108 unique proteins in sTDEVs derived from ablative doses of H-FIRE, which are capable of disrupting the BBB in an in vitro model. Proteomic analysis of TDEVs highlights key changes in pathways related to integrin signaling, Platelet-derived growth factor receptor (PDGFR) signaling, and ubiquitination, which may underline their interactions with brain endothelial cells. These “disruptive” sTDEVs exhibit enhanced tropism for cerebral endothelial cells both in vitro and in vivo, where they persist in the brain longer than sTDEVs released after non-ablative H-FIRE doses. Notably, when introduced into a healthy Fischer rat model, disruptive sTDEVs are associated with increased recruitment of Iba1+ immune cells, suggesting a potential role in modulating post-ablation immune responses. However, despite their altered protein composition, these vesicles do not directly increase BBB permeability in vivo. This study is the first to demonstrate that electroporation-based tumor ablation significantly alters the composition and functionality of tumor-derived extracellular vesicles, potentially influencing the tumor microenvironment post-ablation. These findings have important implications for developing multimodal treatment strategies that combine H-FIRE with systemic therapies to enhance efficacy while managing the peritumoral microenvironment.
Spatial Intracranial Pressure Fields Driven by Blast Overpressure in Rats
Norris, Carly; Murphy, Susan F.; Talty, Caiti-Erin; VandeVord, Pamela J. (Springer, 2024-10-01)
Free-field blast exposure imparts a complex, dynamic response within brain tissue that can trigger a cascade of lasting neurological deficits. Full body mechanical and physiological factors are known to influence the body's adaptation to this seemingly instantaneous insult, making it difficult to accurately pinpoint the brain injury mechanisms. This study examined the intracranial pressure (ICP) profile characteristics in a rat model as a function of blast overpressure magnitude and brain location. Metrics such as peak rate of change of pressure, peak pressure, rise time, and ICP frequency response were found to vary spatially throughout the brain, independent of blast magnitude, emphasizing unique spatial pressure fields as a primary biomechanical component to blast injury. This work discusses the ICP characteristics and considerations for finite element models, in vitro models, and translational in vivo models to improve understanding of biomechanics during primary blast exposure.
Scale modeling of thermo-structural fire tests of multi-orientation wood laminates
Gangi, Michael J.; Lattimer, Brian Y.; Case, Scott W. (Springer, 2024-07-01)
The stacking sequence of laminated wood significantly impacts the composite mechanical behavior of the material, especially when scaling down thermo-mechanical tests on plywood. In previous research, we developed a scaling methodology for thermo-structural tests on samples with similar cross sections, however this paper focused on testing plywood samples with different stacking sequences between the scales. Plywood samples at 1/2 -scale and 1/4 -scale were subjected to combined bending and thermal loading, with the loading scaled to have the same initial static bending stresses. While the 1/4 -scale 4-layer [0 degrees/90 degrees]s laminate and the 1/2 -scale 8-layer [0 degrees/90 degrees/90 degrees/0 degrees]s laminate had an equal number of 0 degrees and 90 degrees layers, as the char front progresses, the sections behave differently. Thus, modeling becomes essential to extrapolating the data from the smaller 1/4 -scale test to predict the behavior of the larger 1/2 -scale test. Reduced cross-sectional area models (RCAM) incorporating classical laminated plate theory were used to predict the mechanical response of the composite samples as the char front increased. Three methods were proposed for calibrating the RCAM models: Fourier number scaling, from detailed kinetics-based pyrolysis GPyro models, and fitting to data from fire exposure thermal response tests. The models calibrated with the experimental char measurements produced the most accurate predictions. The experimental char models validated to predict the behavior of the 1/4 -scale tests within 2.5%, were then able to predict the 1/2 -scale test behavior within 4.5%.
Gait asymmetry persists following unilateral and bilateral total ankle arthroplasty
Carpentier, Stephanie H.; Barylak, Martin; Arena, Sara L.; Queen, Robin M. (Wiley, 2024-11-01)
Total ankle arthroplasty (TAA) improves gait symmetry in patients with unilateral end-stage ankle arthritis but has not been studied in patients undergoing bilateral TAA (B-TAA), and few studies compare TAA patients to control subjects. The purpose of this study was to compare gait symmetry in U-TAA and B-TAA patients and healthy controls. Using prospective databases, 19 unilateral and 19 bilateral ankle arthritis patients undergoing TAA were matched to 19 control subjects by age, sex, and BMI. The Normalized Symmetry Index (NSI) was determined for joint mechanics and ground reaction forces (GRF) during walking trials at a single visit for controls and preoperatively and 1 to 2 years postoperatively for TAA patients. Data was analyzed using linear mixed-effects models to determine differences among time points and cohorts at a significance of alpha = 0.05. Following surgery, B-TAA and U-TAA experienced improved peak plantarflexion moment symmetry (p = 0.017) but remained less symmetric than controls. B-TAA patients had more symmetry than U-TAA patients during peak weight acceptance GRF (p = 0.002), while U-TAA patients had greater peak dorsiflexion symmetry than B-TAA patients. TAA patients demonstrated more asymmetry compared to control subjects for all outcome measures. There was no significant impact of TAA on gait symmetry for GRF or peak ankle angles, and neither U-TAA nor B-TAA was consistently associated with higher gait symmetry. These results indicate that TAA improves symmetry during peak plantarflexion moment, and that significant gait asymmetry persists for B-TAA and U-TAA patients compared to healthy participants.
Instrumented Mouthguard Decoupling Affects Measured Head Kinematic Accuracy
Gellner, Ryan A.; Begonia, Mark T.; Wood, Matthew; Rockwell, Lewis; Geiman, Taylor; Jung, Caitlyn; Rowson, Steven (Springer, 2024-10-01)
Many recent studies have used boil-and-bite style instrumented mouthguards to measure head kinematics during impact in sports. Instrumented mouthguards promise greater accuracy than their predecessors because of their superior ability to couple directly to the skull. These mouthguards have been validated in the lab and on the field, but little is known about the effects of decoupling during impact. Decoupling can occur for various reasons, such as poor initial fit, wear-and-tear, or excessive impact forces. To understand how decoupling influences measured kinematic error, we fit a boil-and-bite instrumented mouthguard to a 3D-printed dentition mounted to a National Operating Committee on Standards for Athletic Equipment (NOCSAE) headform. We also instrumented the headform with linear accelerometers and angular rate sensors at its center of gravity (CG). We performed a series of pendulum impact tests, varying impactor face and impact direction. We measured linear acceleration and angular velocity, and we calculated angular acceleration from the mouthguard and the headform CG. We created decoupling conditions by varying the gap between the lower jaw and the bottom face of the mouthguard. We tested three gap conditions: 0 mm (control), 1.6 mm, and 4.8 mm. Mouthguard measurements were transformed to the CG and compared to the reference measurements. We found that gap condition, impact duration, and impact direction significantly influenced mouthguard measurement error. Error was higher for larger gaps and in frontal (front and front boss) conditions. Higher errors were also found in padded conditions, but the mouthguards did not collect all rigid impacts due to inherent limitations. We present characteristic decoupling time history curves for each kinematic measurement. Exemplary frequency spectra indicating characteristic decoupling frequencies are also described. Researchers using boil-and-bite instrumented mouthguards should be aware of their limitations when interpreting results and should seek to address decoupling through advanced post-processing techniques when possible.
On-Field Evaluation of Mouthpiece-and-Helmet-Mounted Sensor Data from Head Kinematics in Football
Holcomb, Ty D.; Marks, Madison E.; Pritchard, N. Stewart; Miller, Logan E.; Rowson, Steven; Bullock, Garrett S.; Urban, Jillian E.; Stitzel, Joel D. (Springer, 2024-10-01)
Purpose Wearable sensors are used to measure head impact exposure in sports. The Head Impact Telemetry (HIT) System is a helmet-mounted system that has been commonly utilized to measure head impacts in American football. Advancements in sensor technology have fueled the development of alternative sensor methods such as instrumented mouthguards. The objective of this study was to compare peak magnitude measured from high school football athletes dually instrumented with the HIT System and a mouthpiece-based sensor system. Methods Data was collected at all contact practices and competitions over a single season of spring football. Recorded events were observed and identified on video and paired using event timestamps. Paired events were further stratified by removing mouthpiece events with peak resultant linear acceleration below 10 g and events with contact to the facemask or body of athletes. Results A total of 133 paired events were analyzed in the results. There was a median difference (mouthpiece subtracted from HIT System) in peak resultant linear and rotational acceleration for concurrently measured events of 7.3 g and 189 rad/s(2). Greater magnitude events resulted in larger kinematic differences between sensors and a Bland Altman analysis found a mean bias of 8.8 g and 104 rad/s(2), respectively. Conclusion If the mouthpiece-based sensor is considered close to truth, the results of this study are consistent with previous HIT System validation studies indicating low error on average but high scatter across individual events. Future researchers should be mindful of sensor limitations when comparing results collected using varying sensor technologies.
Development of an Injectable Hydrogel for Histotripsy Ablation Toward Future Glioblastoma Therapy Applications
Khan, Zerin Mahzabin; Zhang, Junru; Gannon, Jessica; Johnson, Blake N.; Verbridge, Scott S.; Vlaisavljevich, Eli (Springer, 2024-12-01)
Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. Even after surgery and chemoradiotherapy, residual GBM cells can infiltrate the healthy brain parenchyma to form secondary tumors. To mitigate GBM recurrence, we recently developed an injectable hydrogel that can be crosslinked in the resection cavity to attract, collect, and ablate residual GBM cells. We previously optimized a thiol-Michael addition hydrogel for physical, chemical, and biological compatibility with the GBM microenvironment and demonstrated CXCL12-mediated chemotaxis can attract and entrap GBM cells into this hydrogel. In this study, we synthesize hydrogels under conditions mimicking GBM resection cavities and assess feasibility of histotripsy to ablate hydrogel-encapsulated cells. The results showed the hydrogel synthesis was bio-orthogonal, not shear-thinning, and can be scaled up for injection into GBM resection mimics invitro. Experiments also demonstrated ultrasound imaging can distinguish the synthetic hydrogel from healthy porcine brain tissue. Finally, a 500 kHz transducer applied focused ultrasound treatment to the synthetic hydrogels, with results demonstrating precise histotripsy bubble clouds could be sustained in order to uniformly ablate red blood cells encapsulated by the hydrogel for homogeneous, mechanical fractionation of the entrapped cells. Overall, this hydrogel is a promising platform for biomaterials-based GBM treatment.
Parameter Identification of Soil Material Model for Soil Compaction Under Tire Loading: Laboratory vs. In-Situ Cone Penetrometer Test Data
Shokanbi, Akeem; Jasoliya, Dhruvin; Untaroiu, Costin D. (MDPI, 2025-10-15)
Accurate numerical simulations of soil-tire interactions are essential for optimizing agricultural machinery to minimize soil compaction and enhance crop yield. This study developed and compared two approaches for identifying and validating parameters of a LS-Dyna soil model. The laboratory-based approach derives parameters from triaxial, consolidation, and cone penetrometer tests (CPT), while the optimization-based method refines them using in-situ CPT data via LS-OPT to better capture field variability. Simulations employing Multi-Material Arbitrary Lagrangian–Eulerian (MM-ALE), Smoothed Particle Hydrodynamics (SPH), and Hybrid-SPH methods demonstrate that Hybrid-SPH achieves the optimal balance of accuracy (2% error post-optimization) and efficiency (14-h runtime vs. 22 h for SPH). Optimized parameters improve soil–tire interaction predictions, including net traction and tire sinkage across slip ratios from −10% to 30% (e.g., sinkage of 12.5 mm vs. 11.1 mm experimental at 30% slip, with overall mean-absolute percentage error (MAPE) reduced to 3.5% for sinkage and 4.2% for traction) and rut profiles, outperforming lab-derived values. This framework highlights the value of field-calibrated optimization for sustainable agriculture, offering a cost-effective alternative to field trials for designing low-compaction equipment and reducing yield losses from soil degradation. While sandy loam soil at 0.4% moisture content was used in this study, future extensions to different soil types with varied moisture are recommended.
Characterization of an Advanced Blast Simulator for Investigation of Large Scale Blast Traumatic Brain Injury Studies
Nelson, Allison J.; Ritzel, David; Showalter, Noah; Boppe, Danny; Riegel, Andy; VandeVord, Pamela J. (Springer, 2025-01-01)
Blast traumatic brain injury (bTBI) is a prominent military health concern. The pervasiveness and long-term impacts of this injury highlight the need for investigation of the physiological outcomes of bTBI. Preclinical models allow for the evaluation of behavioral and neuropathological sequelae associated with bTBI. Studies have implemented rodent models to investigate bTBI due to the relative small size and low cost; however, a large animal model with similar neuroanatomical structure to humans is essential for clinical translation. Small blast simulators are used to induce bTBI in rodents, but a large animal model demands a larger device. This study describes a large advanced blast simulator (ABS4) that is a gas-detonation-driven system consisting of 5 sections totaling 40 ft in length with a cross-section of 4 x 4 ft at the test section. It is highly suitable for large animals and human surrogate investigations. This work characterized the ABS4 in preparation of large-scale bTBI testing. An array of tests were conducted with target overpressures in the test section ranging from 10 to 50 psi, and the pressure-time profiles clearly illustrate the essential characteristics of a free-field blast wave, specifically a sharp peak pressure and a defined negative phase. Multiple blast tests conducted at the same target pressure produced very similar pressure profiles, exhibiting the reproducibility of the ABS4 system. With its extensive range of pressures and substantial size, the ABS4 will permit military-relevant translational blast testing.

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