Biomedical Engineering - Research Publications
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ItemRemote Control in Formation of 3D Multicellular Assemblies Using Magnetic Forces(AMER CHEMICAL SOC, 2019-05)Cell constructs have been utilized as building blocks in tissue engineering to closely mimic the natural tissue and also overcome some of the limitations caused by two-dimensional cultures or using scaffolds. External forces can be used to enhance the cells' adhesion and interaction and thus provide better control over production of these structures compared to methods like cell seeding and migration. In this paper, we demonstrate an efficient method to generate uniform, three-dimensional cell constructs using magnetic forces. This method produced spheroids with higher densities and more symmetrical structures than the commonly used centrifugation method for production of cell spheroids. It was also shown that shape of the cell constructs could be changed readily by using different patterns of magnetic field. The application of magnetic fields to impart forces on the cells enhanced the fusion of these spheroids, which could be used to produce larger and more complicated structures for future tissue engineering applications.
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ItemEngineering highly effective antimicrobial selenium nanoparticles through control of particle size(Royal Society of Chemistry, 2019-08-21)The overuse of antibiotics has induced the rapid development of antibiotic resistance in bacteria. As a result, antibiotic efficacy has become limited, and infection with multidrug-resistant bacteria is considered to be one of the largest global human health threats. Consequently, new, effective and safe antimicrobial agents need to be developed urgently. One promising candidate to address this requirement is selenium nanoparticles (Se NPs), which are made from the essential dietary trace element Se and have antimicrobial activity against Gram-positive bacteria. The size of nanomaterials can strongly affect their biophysical properties and functions; however, the effects of the size of Se NPs on their antibacterial efficacy has not been systematically investigated. Therefore, in this work, spherical Se NPs ranging from 43 to 205 nm in diameter were fabricated, and their mammalian cytotoxicity and antibacterial activity as a function of their size were systematically studied. The antibacterial activity of the Se NPs was shown to be strongly size dependent, with 81 nm Se NPs showing the maximal growth inhibition and killing effect of methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). The Se NPs were shown to have multi-modal mechanisms of action that depended on their size, including depleting internal ATP, inducing ROS production, and disrupting membrane potential. All the Se NPs were non-toxic towards mammalian cells up to 25 μg mL−1. Furthermore, the MIC value for the 81 nm particles produced in this research is 16 ± 7 μg mL−1, significantly lower than previously reported MIC values for Se NPs. This data illustrates that Se NP size is a facile yet critical and previously underappreciated parameter that can be tailored for maximal antimicrobial efficacy. We have identified that using Se NPs with a size of 81 nm and concentration of 10 μg mL−1 shows promise as a safe and efficient way to kill S. aureus without damaging mammalian cells.
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ItemNo Preview AvailableDevelopment of Macroporous Chitosan Scaffolds for Eyelid Tarsus Tissue Engineering(Springer Science and Business Media LLC, 2019-12-01)Background: Reconstruction of large eyelid defects remains challenging due to the lack of suitable eyelid tarsus tissue substitutes. We aimed to evaluate a novel bioengineered chitosan scaffold for use as an eyelid tarsus substitute. Methods: Three-dimensional macroporous chitosan hydrogel scaffold were produced via cryogelation with specific biomechanical properties designed to directly match characteristics of native eyelid tarsus tissue. Scaffolds were characterized by confocal microscopy and tensile mechanical testing. To optimise biocompatibility, human eyelid skin fibroblasts were cultured from biopsy-sized samples of fresh eyelid skin. Immunological and gene expression analysis including specific fibroblast-specific markers were used to determine the rate of fibroblast de-differentiation in vitro and characterize cells cultured. Eyelid skin fibroblasts were then cultured over the chitosan scaffolds and the resultant adhesion and growth of cells were characterized using immunocytochemical staining. Results: The chitosan scaffolds were shown to support the attachment and proliferation of NIH 3T3 mouse fibroblasts and human orbital skin fibroblasts in vitro. Our novel bioengineered chitosan scaffold has demonstrated biomechanical compatibility and has the ability to support human eyelid skin fibroblast growth and proliferation. Conclusions: This bioengineered tissue has the potential to be used as a tarsus substitute during eyelid reconstruction, offering the opportunity to pre-seed the patient’s own cells and represents a truly personalised approach to tissue engineering.
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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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ItemEffects of Prophylactic Knee Bracing on Lower Limb Kinematics, Kinetics, and Energetics During Double-Leg Drop Landing at 2 Heights(SAGE PUBLICATIONS INC, 2016-07)BACKGROUND: Anterior cruciate ligament (ACL) injuries commonly occur during landing maneuvers. Prophylactic knee braces were introduced to reduce the risk of ACL injuries, but their effectiveness is debated. HYPOTHESES: We hypothesized that bracing would improve biomechanical factors previously related to the risk of ACL injuries, such as increased hip and knee flexion angles at initial contact and at peak vertical ground-reaction force (GRF), increased ankle plantar flexion angles at initial contact, decreased peak GRFs, and decreased peak knee extension moment. We also hypothesized that bracing would increase the negative power and work of the hip joint and would decrease the negative power and work of the knee and ankle joints. STUDY DESIGN: Controlled laboratory study. METHODS: Three-dimensional motion and force plate data were collected from 8 female and 7 male recreational athletes performing double-leg drop landings from 0.30 m and 0.60 m with and without a prophylactic knee brace. GRFs, joint angles, moments, power, and work were calculated for each athlete with and without a knee brace. RESULTS: Prophylactic knee bracing increased the hip flexion angle at peak GRF by 5.56° (P < .001), knee flexion angle at peak GRF by 4.75° (P = .001), and peak hip extension moment by 0.44 N·m/kg (P < .001). Bracing also increased the peak hip negative power by 4.89 W/kg (P = .002) and hip negative work by 0.14 J/kg (P = .001) but did not result in significant differences in the energetics of the knee and ankle. No differences in peak GRFs and peak knee extension moment were observed with bracing. CONCLUSION: The application of a prophylactic knee brace resulted in improvements in important biomechanical factors associated with the risk of ACL injuries. CLINICAL RELEVANCE: Prophylactic knee braces may help reduce the risk of noncontact knee injuries in recreational and professional athletes while playing sports. Further studies should investigate different types of prophylactic knee braces in conjunction with existing training interventions so that the sports medicine community can better assess the effectiveness of prophylactic knee bracing.
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ItemProphylactic knee bracing alters lower-limb muscle forces during a double-leg drop landing(ELSEVIER SCI LTD, 2016-10-03)Anterior cruciate ligament (ACL) injury can be a painful, debilitating and costly consequence of participating in sporting activities. Prophylactic knee bracing aims to reduce the number and severity of ACL injury, which commonly occurs during landing maneuvers and is more prevalent in female athletes, but a consensus on the effectiveness of prophylactic knee braces has not been established. The lower-limb muscles are believed to play an important role in stabilizing the knee joint. The purpose of this study was to investigate the changes in lower-limb muscle function with prophylactic knee bracing in male and female athletes during landing. Fifteen recreational athletes performed double-leg drop landing tasks from 0.30m and 0.60m with and without a prophylactic knee brace. Motion analysis data were used to create subject-specific musculoskeletal models in OpenSim. Static optimization was performed to calculate the lower-limb muscle forces. A linear mixed model determined that the hamstrings and vasti muscles produced significantly greater flexion and extension torques, respectively, and greater peak muscle forces with bracing. No differences in the timings of peak muscle forces were observed. These findings suggest that prophylactic knee bracing may help to provide stability to the knee joint by increasing the active stiffness of the hamstrings and vasti muscles later in the landing phase rather than by altering the timing of muscle forces. Further studies are necessary to quantify whether prophylactic knee bracing can reduce the load placed on the ACL during intense dynamic movements.