Biomedical Engineering - Research Publications
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ItemAntimicrobial nanoparticle coatings for medical implants: Design challenges and prospects(AMER INST PHYSICS, 2020-11)Microbial colonization, infection, and biofilm formation are major complications in the use of implants and are the predominant risk factors in implant failure. Although aseptic surgery and the administration of antimicrobial drugs may reduce the risk of infection, the systemic use of antibiotics can lead to a lack of efficacy, an increase in the risk of tissue toxicity, and the development of drug-resistant infections. To reduce implant-related infections, antimicrobial materials are increasingly being investigated and applied to implant surfaces using various methods depending on the agents and their microbicidal mechanisms. Through the development of biomaterials and nanotechnology, antimicrobial nanoparticles are becoming promising candidates for implant coatings, as their multifactorial antimicrobial mechanisms combat microbial adherence, viability, and biofilm formation. Despite their antimicrobial promise, the application of nanoparticles onto implant surfaces while retaining their antimicrobial potency faces many challenges. Herein, we review the potential and challenges associated with the design and implementation of antimicrobial nanoparticle coatings for the medical implant industry, particularly focusing on manufacturing considerations, sterilization, long-term stability, protein fouling, regulation, and safety, with a view to providing researchers the necessary tools to aid the translation of materials from the bench to the clinic.
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ItemMultifunctional Antimicrobial Polypeptide-Selenium Nanoparticles Combat Drug-Resistant Bacteria(AMER CHEMICAL SOC, 2020-12-16)Antibiotic-resistant bacteria are a severe threat to human health. The World Health Organization's Global Antimicrobial Surveillance System has revealed widespread occurrence of antibiotic resistance among half a million patients across 22 countries, with Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae being the most common resistant species. Antimicrobial nanoparticles are emerging as a promising alternative to antibiotics in the fight against antimicrobial resistance. In this work, selenium nanoparticles coated with the antimicrobial polypeptide, ε-poly-l-lysine, (Se NP-ε-PL) were synthesized and their antibacterial activity and cytotoxicity were investigated. Se NP-ε-PL exhibited significantly greater antibacterial activity against all eight bacterial species tested, including Gram-positive, Gram-negative, and drug-resistant strains, than their individual components, Se NP and ε-PL. The nanoparticles showed no toxicity toward human dermal fibroblasts at the minimum inhibitory concentrations, demonstrating a therapeutic window. Furthermore, unlike the conventional antibiotic kanamycin, Se NP-ε-PL did not readily induce resistance in E. coli or S. aureus. Specifically, S. aureus began to develop resistance to kanamycin from ∼44 generations, whereas it took ∼132 generations for resistance to develop to Se NP-ε-PL. Startlingly, E. coli was not able to develop resistance to the nanoparticles over ∼300 generations. These results indicate that the multifunctional approach of combining Se NP with ε-PL to form Se NP-ε-PL is a highly efficacious new strategy with wide-spectrum antibacterial activity, low cytotoxicity, and significant delays in development of resistance.
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ItemPredictive Visual Motion Extrapolation Emerges Spontaneously and without Supervision at Each Layer of a Hierarchical Neural Network with Spike-Timing-Dependent Plasticity(SOC NEUROSCIENCE, 2021-05-19)The fact that the transmission and processing of visual information in the brain takes time presents a problem for the accurate real-time localization of a moving object. One way this problem might be solved is extrapolation: using an object's past trajectory to predict its location in the present moment. Here, we investigate how a simulated in silico layered neural network might implement such extrapolation mechanisms, and how the necessary neural circuits might develop. We allowed an unsupervised hierarchical network of velocity-tuned neurons to learn its connectivity through spike-timing-dependent plasticity (STDP). We show that the temporal contingencies between the different neural populations that are activated by an object as it moves causes the receptive fields of higher-level neurons to shift in the direction opposite to their preferred direction of motion. The result is that neural populations spontaneously start to represent moving objects as being further along their trajectory than where they were physically detected. Because of the inherent delays of neural transmission, this effectively compensates for (part of) those delays by bringing the represented position of a moving object closer to its instantaneous position in the world. Finally, we show that this model accurately predicts the pattern of perceptual mislocalization that arises when human observers are required to localize a moving object relative to a flashed static object (the flash-lag effect; FLE).SIGNIFICANCE STATEMENT Our ability to track and respond to rapidly changing visual stimuli, such as a fast-moving tennis ball, indicates that the brain is capable of extrapolating the trajectory of a moving object to predict its current position, despite the delays that result from neural transmission. Here, we show how the neural circuits underlying this ability can be learned through spike-timing-dependent synaptic plasticity and that these circuits emerge spontaneously and without supervision. This demonstrates how the neural transmission delays can, in part, be compensated to implement the extrapolation mechanisms required to predict where a moving object is at the present moment.
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ItemGait compensatory mechanisms in unilateral transfemoral amputees(Elsevier, 2020-03)Individuals with unilateral transfemoral amputation depend on compensatory muscle and joint function to generate motion of the lower limbs, which can produce gait asymmetry; however, the functional role of the intact and residual limb muscles of transfemoral amputees in generating progression, support, and mediolateral balance of the body during walking is not well understood. The aim of this study was to quantify the contributions of the intact and the residual limb's contralateral muscles to body center of mass (COM) acceleration during walking in transfemoral amputees. Three-dimensional subject-specific musculoskeletal models of 6 transfemoral amputees fitted with a socket-type prosthesis were developed and used to quantify muscle forces and muscle contributions to the fore-aft, vertical, and mediolateral body COM acceleration using a pseudo-inverse ground reaction force decomposition method during over-ground walking. Anterior pelvic tilt and hip range of motion in the sagittal and frontal planes of the intact limb was significantly larger than those in the residual limb (p<0.05). The mean contributions of the intact limb hip muscles to body COM support, forward propulsion and mediolateral balance were significantly greater than those in the residual limb (p<0.05). Gluteus maximus contributed more to propulsion and support, while gluteus medius contributed more to balance than other muscles in the intact limb than the residual limb. The findings demonstrate the role of the intact limb hip musculature in compensating for reduced or absent muscles and joint function in the residual limb of transfemoral amputees during walking. The results may be useful in developing rehabilitation programs and design of prostheses to improve gait symmetry and mitigate post-operative musculoskeletal pathology.
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ItemIndividual muscle contributions to hip joint-contact forces during walking in unilateral transfemoral amputees with osseointegrated prostheses(Taylor & Francis, 2020-07-21)Direct skeletal attachment of prostheses in transfemoral amputees circumvents skin-interface complications associated with conventional sockets; however, joint pain and musculoskeletal disease is known to occur postoperatively. This study quantified hip contact forces and the roles of individual muscles in producing hip contact forces during walking in transfemoral amputees with osseointegrated prostheses. Musculoskeletal models were developed for four transfemoral amputees. Gluteus maximus and gluteus medius were the major contributors to the hip contact forces, and the intact limb hip muscles demonstrated greater contributions to hip contact forces than those of the residual limb. The findings may be useful for mitigating walking asymmetry.
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ItemNo Preview AvailableSource data from a systematic review and meta-analysis of EEG and MEG studies investigating functional connectivity in idiopathic generalized epilepsy(ELSEVIER, 2021-12)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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ItemNo Preview AvailableBrain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease(NATURE PORTFOLIO, 2021-12)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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ItemNo Preview AvailableBrainhack: Developing a culture of open, inclusive, community-driven neuroscience(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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ItemNo Preview AvailableLow-Profile Electromagnetic Field Sensors in the Measurement and Modelling of Three-Dimensional Jaw Kinematics and Occlusal Loading(SPRINGER, 2021-06)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.