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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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.
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ItemSubject-specific musculoskeletal modeling in the evaluation of shoulder muscle and joint function(ELSEVIER SCI LTD, 2016-11-07)Upper limb muscle force estimation using Hill-type muscle models depends on musculotendon parameter values, which cannot be readily measured non-invasively. Generic and scaled-generic parameters may be quickly and easily employed, but these approaches do not account for an individual subject's joint torque capacity. The objective of the present study was to develop a subject-specific experimental testing and modeling framework to evaluate shoulder muscle and joint function during activities of daily living, and to assess the capacity of generic and scaled-generic musculotendon parameters to predict muscle and joint function. Three-dimensional musculoskeletal models of the shoulders of 6 healthy subjects were developed to calculate muscle and glenohumeral joint loading during abduction, flexion, horizontal flexion, nose touching and reaching using subject-specific, scaled-generic and generic musculotendon parameters. Muscle and glenohumeral joint forces calculated using generic and scaled-generic models were significantly different to those of subject-specific models (p<0.05), and task dependent; however, scaled-generic model calculations of shoulder glenohumeral joint force demonstrated better agreement with those of subject-specific models during abduction and flexion. Muscles in generic musculoskeletal models operated further from the plateau of their force-length curves than those of scaled-generic and subject-specific models, while muscles in subject-specific models operated over a wider region of their force length curves than those of the generic or scaled-generic models, reflecting diversity of subject shoulder strength. The findings of this study suggest that generic and scaled-generic musculotendon parameters may not provide sufficient accuracy in prediction of shoulder muscle and joint loading when compared to models that employ subject-specific parameter-estimation approaches.
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ItemThe use of laboratory gait analysis for understanding gait deterioration in people with multiple sclerosis(SAGE PUBLICATIONS LTD, 2016-12)Laboratory gait analysis or three-dimensional gait analysis (3DGA), which uses motion capture, force plates and electromyography (EMG), has allowed a better understanding of the underlying mechanisms of gait deterioration in patients with multiple sclerosis (PwMS). This review will summarize the current knowledge on multiple sclerosis (MS)-related changes in kinematics (angles), kinetics (forces) and electromyographic (muscle activation) patterns and how these measures can be used as markers of disease progression. We will also discuss the potential causes of slower walking in PwMS and the implications for 3DGA. Finally, we will describe new technologies and methods that will increase precision and clinical utilization of 3DGA in PwMS. Overall, 3DGA studies have shown that functionality of the ankle joint is the most affected during walking and that compensatory actions to maintain a functional speed may be insufficient in PwMS. However, altered gait patterns may be a strategy to increase stability as balance is also affected in PwMS.
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ItemP015 The effects of cathodal transcranial direct current stimulation in patienst with focal epilepsy (a pilot study)‘(Elsevier, 2017-03)Introduction: Over 65 million people live with epilepsy worldwide. Unfortunately, seizures can not be adequately controlled in a third of the affected individuals. Therefore, there is a definite need for adjunctive or alternative therapeutic approaches in this group of patients to control the recurrence of seizure attacks. Modulation of dysfunctional electrical brain activity by transcranial direct current stimulation (tDCS) seems to be a potentially valuable non-invasive alternative for epilepsy treatment in this population. Objectives: This pilot study aimed to assess the effects of a novel protocol called within-session repeated c-tDCS (9 min treatment - 20 min rest - 9 min treatment) on patients with focal epilepsy. Method: We conducted a small pilot study in patients admitted to the Video-EEG Monitoring Unit at the Royal Melbourne Hospital and as out patients at this hospital or St Vincent Hospital. Thirty patients have participated in this study to date. Twenty patients with focal epilepsy received one session of c-tDCS (9–20-9 protocol) over the temporal lobe in the affected hemisphere. One participant received c-tDCS on two consecutive days. The other nine patients received one session of sham tDCS with the same electrode montage and protocol. Short interval intracortical inhibition or SICI was measured with paired-pulse transcranial magnetic stimulation (TMS) before and after the tDCS intervention in 18 participants. Motor evoked potentials were recorded from first dorsal interosseous muscle in these participants. Participants were asked to record the time and the number of their seizures post tDCS treatment for 4 weeks in a seizure diary. Twenty-four participants returned their diaries. Results: All patients tolerated the c-tDCS protocol very well. One-way ANOVA showed that SICI was increased significantly in the experimental group compared to the sham group (F = 10.3, p = 0.005) (Fig. 1). The mean response ratio was −48.4 (SD = 54) for the experimental group vs. −8.3 (SD = 16.7) for sham group
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ItemCorrelation of in vitro cell adhesion, local shear flow and cell density(ROYAL SOC CHEMISTRY, 2019)Investigating cell adhesion behavior on biocompatible surfaces under dynamic flow conditions is not only of scientific interest but also a principal step towards development of new medical implant materials. Driven by the improvement of the measurement technique for microfluidic flow fields (scanning particle image velocimetry, sPIV), a semi-automatic correlation of the local shear velocity and the cell detachment probability became possible. The functionality of customized software entitled 'PIVDAC' (Particle Image Velocimetry De-Adhesion Correlation) is demonstrated on the basis of detachment measurements using standard sand-blasted titanium implant material. A thermodynamic rate model is applied to describe the process of cell adhesion and detachment. A comparison of the model and our experimental findings, especially in a mild regime, where the shear flow does not simply tear away all cells from the substrate, demonstrates, as predicted, an increase of detachment rate with increasing shear force. Finally, we apply the method to compare experimentally obtained detachment rates under identical flow conditions as a function of cell density and find excellent agreement with previously reported model simulations that consider pure geometrical effects. The demonstrated method opens a wide field of applications to study various cell lines on novel substrates or in time dependent flow fields.