Biomedical Engineering - Research Publications

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    Protein precoating modulates biomolecular coronas and nanocapsule-immune cell interactions in human blood
    Li, S ; Ju, Y ; Zhou, J ; Faria, M ; Ang, C-S ; Mitchell, AJ ; Zhong, Q-Z ; Zheng, T ; Kent, SJ ; Caruso, F (ROYAL SOC CHEMISTRY, 2022-06-09)
    The biomolecular corona that forms on particles upon contact with blood plays a key role in the fate and utility of nanomedicines. Recent studies have shown that precoating nanoparticles with serum proteins can improve the biocompatibility and stealth properties of nanoparticles. However, it is not fully clear how precoating influences biomolecular corona formation and downstream biological responses. Herein, we systematically examine three precoating strategies by coating bovine serum albumin (single protein), fetal bovine serum (FBS, mixed proteins without immunoglobulins), or bovine serum (mixed proteins) on three nanoparticle systems, namely supramolecular template nanoparticles, metal-phenolic network (MPN)-coated template (core-shell) nanoparticles, and MPN nanocapsules (obtained after template removal). The effect of protein precoating on biomolecular corona compositions and particle-immune cell interactions in human blood was characterized. In the absence of a pre-coating, the MPN nanocapsules displayed lower leukocyte association, which correlated to the lower amount (by 2-3 fold) of adsorbed proteins and substantially fewer immunoglobulins (more than 100 times) in the biomolecular corona relative to the template and core-shell nanoparticles. Among the three coating strategies, FBS precoating demonstrated the most significant reduction in leukocyte association (up to 97% of all three nanoparticles). A correlation analysis highlights that immunoglobulins and apolipoproteins may regulate leukocyte recognition. This study demonstrates the impact of different precoating strategies on nanoparticle-immune cell association and the role of immunoglobulins in bio-nano interactions.
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    Evaluation of a lanthanide nanoparticle-based contrast agent for microcomputed tomography of porous channels in subchondral bone
    Silva, MO ; Kirkwood, N ; Mulvaney, P ; Ellis, A ; Stok, KS (WILEY, 2022-05-19)
    Osteoarthritis (OA) is a chronic joint disease that causes disability and pain. The osteochondral interface is a gradient tissue region that plays a significant role in maintaining joint health. It has been shown that during OA, increased neoangiogenesis creates porous channels at the osteochondral interface allowing the transport of molecules related to OA. Importantly, the connection between these porous channels and the early stages of OA development is still not fully understood. Microcomputed tomography (microCT) offers the ability to image the porous channels at the osteochondral interface, however, a contrast agent is necessary to delineate the different X-ray attenuations of the tissues. In this study BaYbF5 -SiO2 nanoparticles are synthesized and optimized as a microCT contrast agent to obtain an appropriate contrast attenuation for subsequent segmentation of structures of interest, that is, porous channels, and mouse subchondral bone. For this purpose, BaYbF5 nanoparticles were synthesized and coated with a biocompatible silica shell (SiO2 ). The optimized BaYbF5 -SiO2 27 nm nanoparticles exhibited the highest average microCT attenuation among the biocompatible nanoparticles tested. The BaYbF5 -SiO2 27 nm nanoparticles increased the mean X-ray attenuation of structures of interest, for example, porous channel models and mouse subchondral bone. The BaYbF5 -SiO2 contrast attenuation was steady after diffusion into mouse subchondral bone. In this study, we obtained for the first time, the average microCT attenuation of the BaYbF5 -SiO2 nanoparticles into porous channel models and mouse subchondral bone. In conclusion, BaYbF5 -SiO2 nanoparticles are a potential contrast agent for imaging porous channels at the osteochondral interface using microCT.
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    Ambient air pollution and epileptic seizures: A panel study in Australia
    Chen, Z ; Yu, W ; Xu, R ; Karoly, PJ ; Maturana, M ; Payne, DE ; Li, L ; Nurse, ES ; Freestone, DR ; Li, S ; Burkitt, AN ; Cook, MJ ; Guo, Y ; Grayden, DB (WILEY, 2022-04-26)
    OBJECTIVE: Emerging evidence has shown that ambient air pollution affects brain health, but little is known about its effect on epileptic seizures. This work aimed to assess the association between daily exposure to ambient air pollution and the risk of epileptic seizures. METHODS: This study used epileptic seizure data from two independent data sources (NeuroVista and Seer App seizure diary). In the NeuroVista data set, 3273 seizures were recorded using intracranial electroencephalography (iEEG) from 15 participants with refractory focal epilepsy in Australia in 2010-2012. In the seizure diary data set, 3419 self-reported seizures were collected through a mobile application from 34 participants with epilepsy in Australia in 2018-2021. Daily average concentrations of carbon monoxide (CO), nitrogen dioxide (NO2 ), ozone (O3 ), particulate matter ≤10 μm in diameter (PM10 ), and sulfur dioxide (SO2 ) were retrieved from the Environment Protection Authority (EPA) based on participants' postcodes. A patient-time-stratified case-crossover design with the conditional Poisson regression model was used to determine the associations between air pollutants and epileptic seizures. RESULTS: A significant association between CO concentrations and epileptic seizure risks was observed, with an increased seizure risk of 4% (relative risk [RR]: 1.04, 95% confidence interval [CI]: 1.01-1.07) for an interquartile range (IQR) increase of CO concentrations (0.13 parts per million), whereas no significant associations were found for the other four air pollutants in the whole study population. Female participants had a significantly increased risk of seizures when exposed to elevated CO and NO2 , with RRs of 1.05 (95% CI: 1.01-1.08) and 1.09 (95% CI: 1.01-1.16), respectively. In addition, a significant association was observed between CO and the risk of subclinical seizures (RR: 1.20, 95% CI: 1.12-1.28). SIGNIFICANCE: Daily exposure to elevated CO concentrations may be associated with an increased risk of epileptic seizures, especially for subclinical seizures.
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    Source data from a systematic review and meta-analysis of EEG and MEG studies investigating functional connectivity in idiopathic generalized epilepsy
    Dharan, AL ; Bowden, SC ; Lai, A ; Peterson, ADH ; Cheung, MW-L ; Woldman, W ; D'Souza, WJ (ELSEVIER, 2021-12-06)
    This article describes source data from a systematic review and meta-analysis of electroencephalography (EEG) and magnetoencephalography (MEG) studies investigating functional connectivity in idiopathic generalized epilepsy. Data selection, analysis and reporting was performed according to PRISMA guidelines. Eligible studies for review were identified from human case-control, and cohort studies. Twenty-two studies were included in the review. Extracted descriptive data included sample characteristics, acquisition of EEG or MEG recordings and network construction. Reported differences between IGE and control groups in functional connectivity or network metrics were extracted as the main outcome measure. Qualitative group differences in functional connectivity were synthesized through narrative review. Meta-analysis was performed for group-level, quantitative estimates of common network metrics clustering coefficient, path length, mean degree and nodal strength. Six studies were included in the meta-analysis. Risk of bias was assessed across all studies. Raw and synthesized data for included studies are reported, alongside effect size and heterogeneity statistics from meta-analyses. Network neurosciences is a rapidly expanding area of research, with significant potential for clinical applications in epilepsy. This data article provides novel, statistical estimates of brain network differences from patients with IGE relative to healthy controls, across the existing literature. Increasing data accessibility supports study replication and improves study comparability for future reviews, enabling a better understanding of network characteristics in IGE.
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    Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease
    Siddiqi, SH ; Schaper, FLWVJ ; Horn, A ; Hsu, J ; Padmanabhan, JL ; Brodtmann, A ; Cash, RFH ; Corbetta, M ; Choi, KS ; Dougherty, DD ; Egorova, N ; Fitzgerald, PB ; George, MS ; Gozzi, SA ; Irmen, F ; Kuhn, AA ; Johnson, KA ; Naidech, AM ; Pascual-Leone, A ; Phan, TG ; Rouhl, RPW ; Taylor, SF ; Voss, JL ; Zalesky, A ; Grafman, JH ; Mayberg, HS ; Fox, MD (NATURE PORTFOLIO, 2021-07-08)
    Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep brain stimulation (n = 101, five datasets). Lesions and stimulation sites most associated with depression severity were connected to a similar brain circuit across all 14 datasets (P < 0.001). Circuits derived from lesions, deep brain stimulation and transcranial magnetic stimulation were similar (P < 0.0005), as were circuits derived from patients with major depression versus other diagnoses (P < 0.001). Connectivity to this circuit predicted out-of-sample antidepressant efficacy of transcranial magnetic stimulation and deep brain stimulation sites (P < 0.0001). In an independent analysis, 29 lesions and 95 stimulation sites converged on a distinct circuit for motor symptoms of Parkinson's disease (P < 0.05). We conclude that lesions, transcranial magnetic stimulation and DBS converge on common brain circuitry that may represent improved neurostimulation targets for depression and other disorders.
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    Brainhack: Developing a culture of open, inclusive, community-driven neuroscience
    Gau, R ; Noble, S ; Heuer, K ; Bottenhorn, KL ; Bilgin, IP ; Yang, Y-F ; Huntenburg, JM ; Bayer, JMM ; Bethlehem, RAI ; Rhoads, SA ; Vogelbacher, C ; Borghesani, V ; Levitis, E ; Wang, H-T ; Van den Bossche, S ; Kobeleva, X ; Legarreta, JH ; Guay, S ; Atay, SM ; Varoquaux, GP ; Huijser, DC ; Sandstrom, MS ; Herholz, P ; Nastase, SA ; Badhwar, A ; Dumas, G ; Schwab, S ; Moia, S ; Dayan, M ; Bassil, Y ; Brooks, PP ; Mancini, M ; Shine, JM ; O'Connor, D ; Xie, X ; Poggiali, D ; Friedrich, P ; Heinsfeld, AS ; Riedl, L ; Toro, R ; Caballero-Gaudes, C ; Eklund, A ; Garner, KG ; Nolan, CR ; Demeter, DV ; Barrios, FA ; Merchant, JS ; McDevitt, EA ; Oostenveld, R ; Craddock, RC ; Rokem, A ; Doyle, A ; Ghosh, SS ; Nikolaidis, A ; Stanley, OW ; Urunuela, E (CELL PRESS, 2021-06-02)
    Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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    Low-Profile Electromagnetic Field Sensors in the Measurement and Modelling of Three-Dimensional Jaw Kinematics and Occlusal Loading
    Woodford, SC ; Robinson, DL ; Edelmann, C ; Mehl, A ; Roehrle, O ; Vee Sin Lee, P ; Ackland, DC (SPRINGER, 2021-01-06)
    Dynamic occlusal loading during mastication is clinically relevant in the design and functional assessment of dental restorations and removable dentures, and in evaluating temporomandibular joint dysfunction. The aim of this study was to develop a modelling framework to evaluate subject-specific dynamic occlusal loading during chewing and biting over the entire dental arch. Measurements of jaw motion were performed on one healthy male adult using low-profile electromagnetic field sensors attached to the teeth, and occlusal anatomy quantified using an intra-oral scanner. During testing, the subject chewed and maximally compressed a piece of rubber between both second molars, first molars, premolars and their central incisors. The occlusal anatomy, rubber geometry and experimentally measured rubber material properties were combined in a finite element model. The measured mandibular motion was used to kinematically drive model simulations of chewing and biting of the rubber sample. Three-dimensional dynamic bite forces and contact pressures across the occlusal surfaces were then calculated. Both chewing and biting on the first molars produced the highest bite forces across the dental arch, and a large amount of anterior shear force was produced at the incisors and the second molars. During chewing, the initial tooth-rubber contact evolved from the buccal sides of the molars to the lingual sides at full mouth closure. Low-profile electromagnetic field sensors were shown to provide a clinically relevant measure of jaw kinematics with sufficient accuracy to drive finite element models of occlusal loading during chewing and biting. The modelling framework presented provides a basis for calculation of physiological, dynamic occlusal loading across the dental arch.
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    Extracellular Matrix Biomimetic Hydrogels, Encapsulated with Stromal Cell-Derived Factor 1, Improve the Composition of Foetal Tissue Grafts in a Rodent Model of Parkinson's Disease
    Penna, V ; Moriarty, N ; Wang, Y ; Law, KCL ; Gantner, CW ; Williams, RJ ; Nisbet, DR ; Parish, CL (MDPI, 2022-05-01)
    Clinical studies have provided evidence for dopamine (DA) cell replacement therapy in Parkinson's Disease. However, grafts derived from foetal tissue or pluripotent stem cells (PSCs) remain heterogeneous, with a high proportion of non-dopaminergic cells, and display subthreshold reinnervation of target tissues, thereby highlighting the need to identify new strategies to improve graft outcomes. In recent work, Stromal Cell-Derived Factor-1 (SDF1), secreted from meninges, has been shown to exert many roles during ventral midbrain DA development and DA-directed differentiation of PSCs. Related, co-implantation of meningeal cells has been shown to improve neural graft outcomes, however, no direct evidence for the role of SDF1 in neural grafting has been shown. Due to the rapid degradation of SDF1 protein, here, we utilised a hydrogel to entrap the protein and sustain its delivery at the transplant site to assess the impact on DA progenitor differentiation, survival and plasticity. Hydrogels were fabricated from self-assembling peptides (SAP), presenting an epitope for laminin, the brain's main extracellular matrix protein, thereby providing cell adhesive support for the grafts and additional laminin-integrin signalling to influence cell fate. We show that SDF1 functionalised SAP hydrogels resulted in larger grafts, containing more DA neurons, increased A9 DA specification (the subpopulation of DA neurons responsible for motor function) and enhanced innervation. These findings demonstrate the capacity for functionalised, tissue-specific hydrogels to improve the composition of grafts targeted for neural repair.
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    The Potential of Calcium Phosphate Nanoparticles as Adjuvants and Vaccine Delivery Vehicles
    Sun, Z ; Li, W ; Lenzo, JC ; Holden, JA ; McCullough, MJ ; O'Connor, AJ ; O'Brien-Simpson, NM (FRONTIERS MEDIA SA, 2021-12-22)
    Vaccination is one of the most efficacious and cost-effective ways to protect people from infectious diseases and potentially cancer. The shift in vaccine design from disrupted whole pathogens to subunit antigens has brought attention on to vaccine delivery materials. For the last two decades, nanotechnology-based vaccines have attracted considerable attention as delivery vehicles and adjuvants to enhance immunogenicity, exemplified with the current COVID vaccines. The nanoparticle vaccines display unique features in protecting antigens from degradation, controlled antigen release and longer persisting immune response. Due to their size, shape and surface charge, they can be outstanding adjuvants to achieve various immunological effects. With the safety and biodegradable benefit of calcium phosphate nanoparticles (CaP NPs), they are an efficient carrier for vaccine design and adjuvants. Several research groups have studied CaP NPs in the field of vaccination with great advances. Although there are several reports on the overview of CaP NPs, they are limited to the application in biomedicine, drug delivery, bone regeneration and the methodologies of CaP NPs synthesis. Hence, we summarised the basic properties of CaP NPs and the recent vaccine development of CaP NPs in this review.
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    Multi-timepoint pattern analysis: Influence of personality and behavior on decoding context-dependent brain connectivity dynamics
    Ganesan, S ; Lv, J ; Zalesky, A (WILEY, 2021-12-03)
    Behavioral traits are rarely considered in task-evoked functional magnetic resonance imaging (MRI) studies, yet these traits can affect how an individual engages with the task, and thus lead to heterogeneity in task-evoked brain responses. We aimed to investigate whether interindividual variation in behavior associates with the accuracy of predicting task-evoked changes in the dynamics of functional brain connectivity measured with functional MRI. We developed a novel method called multi-timepoint pattern analysis (MTPA), in which binary logistic regression classifiers were trained to distinguish rest from each of 7 tasks (i.e., social cognition, working memory, language, relational, motor, gambling, emotion) based on functional connectivity dynamics measured in 1,000 healthy adults. We found that connectivity dynamics for multiple pairs of large-scale networks enabled individual classification between task and rest with accuracies exceeding 70%, with the most discriminatory connections relatively unique to each task. Crucially, interindividual variation in classification accuracy significantly associated with several behavioral, cognition and task performance measures. Classification between task and rest was generally more accurate for individuals with higher intelligence and task performance. Additionally, for some of the tasks, classification accuracy improved with lower perceived stress, lower aggression, higher alertness, and greater endurance. We conclude that heterogeneous dynamic adaptations of functional brain networks to changing cognitive demands can be reliably captured as linearly separable patterns by MTPA. Future studies should account for interindividual variation in behavior when investigating context-dependent dynamic functional connectivity.