Scholarly Works, Biomedical Engineering and Mechanics

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  • Ultrasonic Bubble Cleaner as a Sustainable Solution
    Howell, Justin; Ham, Emerson; Jung, Sunghwan (MDPI, 2023-10-28)
    We aim to develop a floor-cleaning design by exploiting oscillating bubbles combined with ambient pressure waves to clean various surfaces. Previous studies of this method in lab settings have proven its efficacy, but practical applications, especially concerning real-world conditions like dirt surfaces, remain largely unprobed. Our findings indicate that, excluding a configuration with a heavy mass bottom transducer, all tested configurations achieved approximately 60–70% cleaning performance. A slight improvement in cleaning performance was observed with the introduction of microbubbles, although it was within the error margin. Particularly noteworthy is the substantial reduction in water consumption in configurations with a water pocket, decreasing from 280 mL to a mere 3 mL, marking a significant step toward more environmentally sustainable cleaning practices, such as reduced water usage. This research provides implications for real-world cleaning applications, promising an eco-friendly and efficient cleaning alternative that reduces water usage and handles a variety of materials without causing damage.
  • Efferocytosis is restricted by axon guidance molecule EphA4 via ERK/Stat6/MERTK signaling following brain injury
    Soliman, Eman; Leonard, John; Basso, Erwin K. G.; Gershenson, Ilana; Ju, Jing; Mills, Jatia; de Jager, Caroline; Kaloss, Alexandra M.; Elhassanny, Mohamed; Pereira, Daniela; Chen, Michael; Wang, Xia; Theus, Michelle H. (2023-11-09)
    Background Efferocytosis is a process that removes apoptotic cells and cellular debris. Clearance of these cells alleviates neuroinflammation, prevents the release of inflammatory molecules, and promotes the production of anti-inflammatory cytokines to help maintain tissue homeostasis. The underlying mechanisms by which this occurs in the brain after injury remain ill-defined. Methods We used GFP bone marrow chimeric knockout (KO) mice to demonstrate that the axon guidance molecule EphA4 receptor tyrosine kinase is involved in suppressing MERTK in the brain to restrict efferocytosis of resident microglia and peripheral-derived monocyte/macrophages. Results Single-cell RNAseq identified MERTK expression, the primary receptor involved in efferocytosis, on monocytes, microglia, and a subset of astrocytes in the damaged cortex following brain injury. Loss of EphA4 on infiltrating GFP-expressing immune cells improved functional outcome concomitant with enhanced efferocytosis and overall protein expression of p-MERTK, p-ERK, and p-Stat6. The percentage of GFP+ monocyte/macrophages and resident microglia engulfing NeuN+ or TUNEL+ cells was significantly higher in KO chimeric mice. Importantly, mRNA expression of Mertk and its cognate ligand Gas6 was significantly elevated in these mice compared to the wild-type. Analysis of cell-specific expression showed that p-ERK and p-Stat6 co-localized with MERTK-expressing GFP + cells in the peri-lesional area of the cortex following brain injury. Using an in vitro efferocytosis assay, co-culturing pHrodo-labeled apoptotic Jurkat cells and bone marrow (BM)-derived macrophages, we demonstrate that efferocytosis efficiency and mRNA expression of Mertk and Gas6 was enhanced in the absence of EphA4. Selective inhibitors of ERK and Stat6 attenuated this effect, confirming that EphA4 suppresses monocyte/macrophage efferocytosis via inhibition of the ERK/Stat6 pathway. Conclusions Our findings implicate the ERK/Stat6/MERTK axis as a novel regulator of apoptotic debris clearance in brain injury that is restricted by peripheral myeloid-derived EphA4 to prevent the resolution of inflammation.
  • Megakaryocyte-induced contraction of plasma clots: Cellular mechanisms and structural mechanobiology
    Kim, Oleg V.; Litvinov, Rustem I.; Gagne, Alyssa L.; French, Deborah L.; Brass, Lawrence F.; Weisel, John W. (American Society of Hematology, 2023)
    Non-muscle cell contractility is an essential feature underlying diverse cellular processes such as motility, morphogenesis, division and genome replication, intracellular transport, and secretion. Blood clot contraction is a well-studied process driven by contracting platelets. Megakaryocytes, which are the precursors to platelets, can be found in the bone marrow and in the lungs. Although they express many of the same proteins and structures found in platelets, little is known about their ability to engage with extracellular proteins such as fibrin and contract. Here we have measured the ability of megakaryocytes to compress plasma clots. Megakaryocytes derived from human induced pluripotent stem cells (iMKs) were suspended in human platelet-free blood plasma and stimulated with thrombin. Using real-time macroscale optical tracking, confocal microscopy, and biomechanical measurements, we found that activated iMKs caused macroscopic volumetric clot shrinkage, as well as densification and stiffening of the fibrin network via fibrin-attached plasma membrane protrusions undergoing extension-retraction cycles that cause shortening and bending of fibrin fibers. Contraction induced by iMKs involved two kinetic phases with distinct rates and durations. It was suppressed by inhibitors of non-muscle myosin IIA, actin polymerization, and integrin αIIbβ3-fibrin interactions, indicating that the molecular mechanisms of iMK contractility were similar or identical to those in activated platelets. Our findings provide new insights into megakaryocyte biomechanics and suggest that iMKs can be used as a model system to study platelet contractility. Physiologically, the ability of MKs to contract plasma clots may play a role in the mechanical remodeling of intravascular blood clots and thrombi.
  • Combined computational modeling and experimental study of the biomechanical mechanisms of platelet-driven contraction of fibrin clots
    Michael, Christian; Pancaldi, Francesco; Britton, Samuel; Kim, Oleg V.; Peshkova, Alina D.; Vo, Khoi; Xu, Zhiliang; Litvinov, Rustem I.; Weisel, John W.; Alber, Mark (Nature Portfolio, 2023-08-24)
    While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction or retraction. Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. Recently, blood clot contraction was observed to be hindered in patients with COVID-19. A three-dimensional multiscale computational model is developed and used to quantify biomechanical mechanisms of the kinetics of clot contraction driven by platelet-fibrin pulling interactions. These results provide important biological insights into contraction of platelet filopodia, the mechanically active thin protrusions of the plasma membrane, described previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach described can potentially apply to studying other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness.
  • Ablative and Immunostimulatory Effects of Histotripsy Ablation in a Murine Osteosarcoma Model
    Hay, Alayna N.; Imran, Khan Mohammad; Hendricks-Wenger, Alissa; Gannon, Jessica M.; Sereno, Jacqueline; Simon, Alex; Lopez, Victor A.; Coutermarsh-Ott, Sheryl; Vlaisavljevich, Eli; Allen, Irving C.; Tuohy, Joanne L. (MDPI, 2023-10-09)
    Background: Osteosarcoma (OS) is the most frequently occurring malignant bone tumor in humans, primarily affecting children and adolescents. Significant advancements in treatment options for OS have not occurred in the last several decades, and the prognosis remains grim with only a 70% rate of 5-year survival. The objective of this study was to investigate the focused ultrasound technique of histotripsy as a novel, noninvasive treatment option for OS. Methods: We utilized a heterotopic OS murine model to establish the feasibility of ablating OS tumors with histotripsy in a preclinical setting. We investigated the local immune response within the tumor microenvironment (TME) via immune cell phenotyping and gene expression analysis. Findings: We established the feasibility of ablating heterotopic OS tumors with ablation characterized microscopically by loss of cellular architecture in targeted regions of tumors. We observed greater populations of macrophages and dendritic cells within treated tumors and the upregulation of immune activating genes 72 h after histotripsy ablation. Interpretation: This study was the first to investigate histotripsy ablation for OS in a preclinical murine model, with results suggesting local immunomodulation within the TME. Our results support the continued investigation of histotripsy as a novel noninvasive treatment option for OS patients to improve clinical outcomes and patient prognosis.
  • Profiling renal dysfunction using Raman chemometric urinalysis, with special reference to COVID19, lupus nephritis, and diabetic nephropathy
    Robertson, John L.; Issa, Amr Sayed; Gomez, Mariana; Sullivan, Kathleen; Senger, Ryan S. (Knowledge Enterprise Journals, 2023-09-30)
    Background: Many systemic and urinary tract diseases alter renal structure and function, including changing the composition of urine. While routine urinalysis (physical properties, sediment evaluation, urine chemistry analytes) is useful in screening, it has limitations on separating disease processes, structural changes, and functional abnormalities. Likewise, while many individual ‘biomarkers’ have been used to screen for disease, they have not met with widespread clinical adoption. The recent COVID19 Pandemic and the recognition of post-acute sequelae SARS-CoV-2 infection (PASC) have highlighted the need for rapid, scalable, economical, and accurate screening tools for managing disease. Aims: Validate a Raman spectroscopy-based screening technology for urine analysis that could be used for recognition and quantification of systemic and renal effects of acute and PASC COVID19 disease. Methods: One hundred ten (110) urine specimens were obtained from consented adults diagnosed with COVID19 disease by RT-PCR and/or proximate (household) contact With RT-PCR-confirmed COVID19 disease. Samples were analyzed using Raman chemometric urinalysis, a technology that detects hundreds of discrete chemicals in urine and applies computational comparison-machine learning to detect COVID19-associated molecular patterns (‘fingerprints’). Results: When compared with the urine multimolecular ‘fingerprints’ of healthy individuals and patients with known systemic diseases (diabetes mellitus, lupus) that alter renal structure and function, patients with acute and PASC COVID19 had unique ‘fingerprints’ indicative of alterations in renal function (i.e. – infection altered urine composition). Differences in disease severity (mild to severe) were reflected by different ‘fingerprints’ in urine. Roughly 20% of hospitalized patients developed a degree of renal dysfunction (decrements in eGFR) that were correlated with distinct changes in urine fingerprints. Conclusion: Raman chemometric urinalysis may be a useful tool in management of patients with COVID19 disease, particularly in detecting patients with evolving renal dysfunction for whom there should be attention to medication use and renal health restoration/preservation.
  • Development of a multiphase perfusion model for biomimetic reduced-order dense tumors
    Akash, Mohammad Mehedi Hasan; Chakraborty, Nilotpal; Mohammad, Jiyan; Reindl, Katie; Basu, Saikat (Springer Nature, 2023-03)
    Dense fibrous extracellular constitution of solid tumors exerts high resistance to diffusive transport into it; additionally, the scarcity of blood and lymphatic flows hinders convection. The complexity of fluidic transport mechanisms in such tumor environments still presents open questions with translational end goals. For example, clinical diagnosis and targeted drug delivery platforms for such dense tumors can ideally benefit from a quantitative framework on plasma uptake into the tumor. In this study, we present a computational model for physical parameters that may influence blood percolation and penetration into simple biomimetic solid tumor geometry. The model implements three-phase viscous-laminar transient simulation to mimic the transport physics inside a tumor-adhering blood vessel and measures the constituent volume fractions of the three considered phases, viz. plasma, RBCs (red blood cells, also known as "erythrocytes "), and WBCs (white blood cells, also known as "leukocytes ") at three different flow times, while simultaneously recording the plasma pressure and velocity at the entry point to the tumor's extracellular space. Subsequently, to quantify plasma perfusion within the tumor zone, we proposed a reduced-order two-dimensional transport model for the tumor entry zone and its extracellular space for three different fenestra diameters: 0.1, 0.3, and 0.5 mu m; the simulations were two-phase viscous-laminar transient. The findings support the hypothesis that plasma percolation into the tumor is proportional to the leakiness modulated by the size of fenestra openings, and the rate of percolation decays with the diffusion distance.
  • Complex hemolymph circulation patterns in grasshopper wings
    Salcedo, Mary K.; Jun, Brian H.; Socha, John J.; Pierce, Naomi E.; Vlachos, Pavlos P.; Combes, Stacey A. (Nature Portfolio, 2023-03)
    An insect's living systems-circulation, respiration, and a branching nervous system-extend from the body into the wing. Wing hemolymph circulation is critical for hydrating tissues and supplying nutrients to living systems such as sensory organs across the wing. Despite the critical role of hemolymph circulation in maintaining healthy wing function, wings are often considered "lifeless" cuticle, and flows remain largely unquantified. High-speed fluorescent microscopy and particle tracking of hemolymph in the wings and body of the grasshopper Schistocerca americana revealed dynamic flow in every vein of the fore- and hindwings. The global system forms a circuit, but local flow behavior is complex, exhibiting three distinct types: pulsatile, aperiodic, and "leaky" flow. Thoracic wing hearts pull hemolymph from the wing at slower frequencies than the dorsal vessel; however, the velocity of returning hemolymph (in the hindwing) is faster than in that of the dorsal vessel. To characterize the wing's internal flow mechanics, we mapped dimensionless flow parameters across the wings, revealing viscous flow regimes. Wings sustain ecologically important insect behaviors such as pollination and migration. Analysis of the wing circulatory system provides a template for future studies investigating the critical hemodynamics necessary to sustaining wing health and insect flight. Study of grasshopper wings shows that hemolymph flows through every vein in the insect wing, creating a broad circuitous flow pattern in the wings, with three different flow behaviours (pulsatile, leaky, aperiodic).
  • High-Frequency Dielectrophoresis Reveals That Distinct Bio-Electric Signatures of Colorectal Cancer Cells Depend on Ploidy and Nuclear Volume
    Duncan, Josie L.; Bloomfield, Mathew; Swami, Nathan; Cimini, Daniela; Davalos, Rafael V. (MDPI, 2023-09-01)
    Aneuploidy, or an incorrect chromosome number, is ubiquitous among cancers. Whole-genome duplication, resulting in tetraploidy, often occurs during the evolution of aneuploid tumors. Cancers that evolve through a tetraploid intermediate tend to be highly aneuploid and are associated with poor patient prognosis. The identification and enrichment of tetraploid cells from mixed populations is necessary to understand the role these cells play in cancer progression. Dielectrophoresis (DEP), a label-free electrokinetic technique, can distinguish cells based on their intracellular properties when stimulated above 10 MHz, but DEP has not been shown to distinguish tetraploid and/or aneuploid cancer cells from mixed tumor cell populations. Here, we used high-frequency DEP to distinguish cell subpopulations that differ in ploidy and nuclear size under flow conditions. We used impedance analysis to quantify the level of voltage decay at high frequencies and its impact on the DEP force acting on the cell. High-frequency DEP distinguished diploid cells from tetraploid clones due to their size and intracellular composition at frequencies above 40 MHz. Our findings demonstrate that high-frequency DEP can be a useful tool for identifying and distinguishing subpopulations with nuclear differences to determine their roles in disease progression.
  • Unsupervised Multitaper Spectral Method for Identifying REM Sleep in Intracranial EEG Recordings Lacking EOG/EMG Data
    Lepage, Kyle Q.; Jain, Sparsh; Kvavilashvili, Andrew; Witcher, Mark; Vijayan, Sujith (MDPI, 2023-08-25)
    A large number of human intracranial EEG (iEEG) recordings have been collected for clinical purposes, in institutions all over the world, but the vast majority of these are unaccompanied by EOG and EMG recordings which are required to separate Wake episodes from REM sleep using accepted methods. In order to make full use of this extremely valuable data, an accurate method of classifying sleep from iEEG recordings alone is required. Existing methods of sleep scoring using only iEEG recordings accurately classify all stages of sleep, with the exception that wake (W) and rapid-eye movement (REM) sleep are not well distinguished. A novel multitaper (Wake vs. REM) alpha-rhythm classifier is developed by generalizing K-means clustering for use with multitaper spectral eigencoefficients. The performance of this unsupervised method is assessed on eight subjects exhibiting normal sleep architecture in a hold-out analysis and is compared against a classical power detector. The proposed multitaper classifier correctly identifies 36±6 min of REM in one night of recorded sleep, while incorrectly labeling less than 10% of all labeled 30 s epochs for all but one subject (human rater reliability is estimated to be near 80%), and outperforms the equivalent statistical-power classical test. Hold-out analysis indicates that when using one night’s worth of data, an accurate generalization of the method on new data is likely. For the purpose of studying sleep, the introduced multitaper alpha-rhythm classifier further paves the way to making available a large quantity of otherwise unusable IEEG data.
  • Exploratory Development of Algorithms for Determining Driver Attention Status
    Herbers, Eileen; Miller, Marty; Neurauter, Luke; Walters, Jacob; Glaser, Daniel (SAGE, 2023-09)
    Objective: Varying driver distraction algorithms were developed using vehicle kinematics and driver gaze data obtained from a camera-based driver monitoring system (DMS). Background: Distracted driving characteristics can be difficult to accurately detect due to wide variation in driver behavior across driving environments. The growing availability of information about drivers and their involvement in the driving task increases the opportunity for accurately recognizing attention state. Method: A baseline for driver distraction levels was developed using a video feed of 24 separate drivers in varying naturalistic driving conditions. This initial assessment was used to develop four buffer-based algorithms that aimed to determine a driver's real-time attentiveness, via a variety of metrics and combinations thereof. Results: Of those tested, the optimal algorithm included ungrouped glance locations and speed. Notably, as an algorithm's performance of detecting very distracted drivers improved, its accuracy for correctly identifying attentive drivers decreased. Conclusion: At a minimum, drivers' gaze position and vehicle speed should be included when designing driver distraction algorithms to delineate between glance patterns observed at high and low speeds. Distraction algorithms should be designed with an understanding of their limitations, including instances in which they may fail to detect distracted drivers, or falsely notify attentive drivers. Application: This research adds to the body of knowledge related to driver distraction and contributes to available methods to potentially address and reduce occurrences. Machine learning algorithms can build on the data elements discussed to increase distraction detection accuracy using robust artificial intelligence.
  • Pericyte Progenitor Coupling to the Emerging Endothelium during Vasculogenesis via Connexin43
    Payne, Laura Beth; Tewari, Bhanu P.; Dunkenberger, Logan; Bond, Samantha; Savelli, Alyssa; Darden, Jordan; Zhao, Huaning; Willi, Caroline; Kanodia, Ronak; Gude, Rosalie; Powell, Michael D.; Oestreich, Kenneth J.; Sontheimer, Harald; Dal-Pra, Sophie; Chappell, John C. (Lippincott Williams & Wilkins, 2022-04-01)
    Background: Vascular pericytes stabilize blood vessels and contribute to their maturation, while playing other key roles in microvascular function. Nevertheless, relatively little is known about involvement of their precursors in the earliest stages of vascular development, specifically during vasculogenesis. Methods: We combined high-power, time-lapse imaging with transcriptional profiling of emerging pericytes and endothelial cells in reporter mouse and cell lines. We also analyzed conditional transgenic animals deficient in Cx43/Gja1 (connexin 43/gap junction alpha-1) expression within Ng2+ cells. Results: A subset of Ng2-DsRed+ cells, likely pericyte/mural cell precursors, arose alongside endothelial cell differentiation and organization and physically engaged vasculogenic endothelium in vivo and in vitro. We found no overlap between this population of differentiating pericyte/mural progenitors and other lineages including hemangiogenic and neuronal/glial cell types. We also observed cell-cell coupling and identified Cx43-based gap junctions contributing to pericyte-endothelial cell precursor communication during vascular assembly. Genetic loss of Cx43/Gja1 in Ng2+ pericyte progenitors compromised embryonic blood vessel formation in a subset of animals, while surviving mutants displayed little-to-no vessel abnormalities, suggesting a resilience to Cx43/Gja1 loss in Ng2+ cells or potential compensation by additional connexin isoforms. Conclusions: Together, our data suggest that a distinct pericyte lineage emerges alongside vasculogenesis and directly communicates with the nascent endothelium via Cx43 during early vessel formation. Cx43/Gja1 loss in pericyte/mural cell progenitors can induce embryonic vessel dysmorphogenesis, but alternate connexin isoforms may be able to compensate. These data provide insight that may reshape the current framework of vascular development and may also inform tissue revascularization/vascularization strategies.
  • Focused ultrasound for the remote modulation of nitric oxide release from injectable PEG-fibrinogen hydrogels for tendon repair
    Meyers, Kaylee M.; Simon, Alex; Khan, Zerin M.; Rajachar, Rupak M.; Vlaisavljevich, Eli (Frontiers, 2023-04)
    Introduction: Tendon disorders such as tendinosis, the degradation of collagen in tendon, or tendonitis, inflammation of tendon tissue, contribute to 30% of musculoskeletal complaints. To address the limitations of currently available treatments for tendon repair, an injectable polyethylene glycol (PEG)fibrinogen hydrogel encompassing nitric oxide (NO) releasing mu-particles was generated. The release of nitric oxide, a therapeutic molecule that modulates many wound healing processes, from the hydrogel can be modified with thermal and mechanical stimulus. To achieve remote control over NO release from hydrogels after deployment, focused ultrasound (FUS) was explored as it provides highly controlled thermal and mechanical stimulus non-invasively. Methods: In this work, the ability of FUS to remotely elicit on-demand NO generation from acoustically active composite hydrogels via thermal and/or mechanical stimulus was explored. Specifically, the temperature and timedependent release of NO was simulated and characterized when applying FUS to composite hydrogels. Results: Results from acoustic simulations as well as thermocouple heating studies indicated that high spatial and temporal control over hydrogel warming could be achieved non-invasively with a 3.5 MHz FUS transducer. FUS was also able to remotely control NO release from hydrogels with various thermal magnitudes and durations. Additionally, no apparent changes in the mechanical properties of hydrogels were observed with FUS treatment. Discussion: Utilizing FUS thermal and mechanical stimulus provides a potential method of remotely controlling NO release from hydrogels at a wound site to aid in tendon repair.
  • Editorial: 'Engineering the Tumor Immune Microenvironment' Special Issue
    Ahmad, Raffae N.; Verbridge, Scott S. (MDPI, 2023-08-08)
    Cancer immunotherapies, while promising and occasionally even curative, encounter numerous hurdles within the tumor microenvironment that hinder their efficacy [...]
  • Transient use of hemolymph for hydraulic wing expansion in cicadas
    Salcedo, Mary K.; Ellis, Tyler E.; Saenz, Angela S.; Lu, Joyce; Worrell, Terrell; Madigan, Michael L.; Socha, John J. (Nature Portfolio, 2023-04)
    Insect wings must be flexible, light, and strong to allow dynamic behaviors such as flying, mating, and feeding. When winged insects eclose into adults, their wings unfold, actuated hydraulically by hemolymph. Flowing hemolymph in the wing is necessary for functioning and healthy wings, both as the wing forms and as an adult. Because this process recruits the circulatory system, we asked, how much hemolymph is pumped into wings, and what happens to the hemolymph afterwards? Using Brood X cicadas (Magicicada septendecim), we collected 200 cicada nymphs, observing wing transformation over 2 h. Using dissection, weighing, and imaging of wings at set time intervals, we found that within 40 min after emergence, wing pads morphed into adult wings and total wing mass increased to similar to 16% of body mass. Thus, a significant amount of hemolymph is diverted from body to wings to effectuate expansion. After full expansion, in the similar to 80 min after, the mass of the wings decreased precipitously. In fact, the final adult wing is lighter than the initial folded wing pad, a surprising result. These results demonstrate that cicadas not only pump hemolymph into the wings, they then pump it out, producing a strong yet lightweight wing.
  • Identifying Factors for Designing a Successful Interactive Telemedical Training System for Remote Pediatric Physical Exams
    Morshedzadeh, Elham; Muelenaer, Andre; Morris, Michelle; Werlich, Dana; Nelson, Margaret (Cumulus Association, 2021)
    During the 2020 pandemic, telemedical consultation became a core tool for continuous access to healthcare. However, the skills required of medical teams to provide pediatric healthcare through telehealth are new and undeveloped. To address these issues, our pilot study focused on the interaction between the nurse, patient, and provider with telehealth technology. This study sought to provide evidence that training protocols for operation of a telemedicine system such as a telemedicine cart and its corresponding attachments are highly effective. Based on our results, users (nurse and provider) need to be familiar with the functions of the cart and its components. This suggests that an interactive training system consisting of hands-on learning and augmented reality can elevate a pediatric telemedicine visit, from a video call to a comprehensive physical exam. This research received a “Pilot Translational and Clinical Studies Program” grant from the US National Institutes of Health in October 2020.
  • Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation
    Campana, Luca G.; Daud, Adil; Lancellotti, Francesco; Arroyo, Julio P.; Davalos, Rafael V.; Di Prata, Claudia; Gehl, Julie (MDPI, 2023-06-25)
    The 4th World Congress of Electroporation (Copenhagen, 9–13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.
  • Catheter-based Medical Device Biofilm Ablation Using Histotripsy: A Parameter Study
    Morse, Ryan; Childers, Christopher; Nowak, Elizabeth; Rao, Jayasimha; Vlaisavljevich, Eli (Elsevier, 2023-07-01)
    OBJECTIVE: Biofilm formation in medical catheters is a major source of hospital-acquired infections which can produce increased morbidity and mortality for patients. Histotripsy is a non-invasive, non-thermal focused ultrasound therapy and recently has been found to be effective at removal of biofilm from medical catheters. Previously established histotripsy methods for biofilm removal, however, would require several hours of use to effectively treat a full-length medical catheter. Here, we investigate the potential to increase the speed and efficiency with which biofilms can be ablated from catheters using histotripsy. METHODS: Pseudomonas aeruginosa (PA14) biofilms were cultured in in vitro Tygon catheter mimics and treated with histotripsy using a 1 MHz histotripsy transducer and a variety of histotripsy pulsing rates and scanning methods. The improved parameters identified in these studies were then used to explore the bactericidal effect of histotripsy on planktonic PA14 suspended in a catheter mimic. RESULTS: Histotripsy can be used to remove biofilm and kill bacteria at substantially increased speeds compared with previously established methods. Near-complete biofilm removal was achieved at treatment speeds up to 1 cm/s, while a 4.241 log reduction in planktonic bacteria was achieved with 2.4 cm/min treatment. CONCLUSION: These results represent a 500-fold increase in biofilm removal speeds and a 6.2-fold increase in bacterial killing speeds compared with previously published methods. These findings indicate that histotripsy shows promise for the treatment of catheter-associated biofilms and planktonic bacteria in a clinically relevant time frame.
  • Mechanics of removing water from the ear canal: Rayleigh-Taylor instability
    Kim, Seungho; Baskota, Anuj; Kang, Hosung; Jung, Sunghwan (Cambridge University Press, 2023-05)
    Water stuck in the ear is a common problem during showering, swimming or other water activities. Having water trapped in the ear canal for a long time can lead to ear infections and possibly result in hearing loss. A common strategy for emptying water from the ear canal is to shake the head, where high acceleration helps remove the water. In this present study, we rationalize the underlying mechanism of water ejection/removal from the ear canal by performing experiments and developing a stability theory. From the experiments, we measure the critical acceleration to remove the trapped water inside different sizes of canals. Our theoretical model, modified from the Rayleigh-Taylor instability, can explain the critical acceleration observed in experiments, which strongly depends on the radius of the ear canal. The resulting critical acceleration tends to increase, especially in smaller ear canals, which indicates that shaking heads for water removal can be more laborious and potentially threatening to children due to their small size of the ear canal compared with adults.