Trinity Center for Bioengineering

Dublin, Ireland

Trinity Center for Bioengineering

Dublin, Ireland
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Mc Govern E.M.,St Vincents University Hospital | Mc Govern E.M.,University College Dublin | Mc Govern E.M.,Trinity Center for Bioengineering | O'Connor E.,St Vincents University Hospital | And 17 more authors.
Physiological Measurement | Year: 2017

The temporal discrimination threshold (TDT) is a proposed pre-clinical biomarker (endophenotype) for adult onset isolated focal dystonia (AOIFD). Age- and sex-related effects on temporal discrimination demonstrate that women, before the age of 40 years, have faster temporal discrimination than men but their TDTs worsen with age at almost three times the rate of men. Thus after 40 years the TDT in women is progressively worse than in men. AOIFD is an increasingly female-predominant disorder after the age of 40; it is not clear whether this age-related sexually-dimorphic difference observed for both the TDT and sex ratio at disease onset in AOIFD is a hormonal or chromosomal effect. The aim of this study was to examine temporal discrimination at weekly intervals during two consecutive menstrual cycles in 14 healthy female volunteers to determine whether physiological hormonal changes affected temporal discrimination. We observed no significant differences in weekly temporal discrimination threshold values during the menstrual cycles and no significant correlation with the menstrual cycle stage. This observed stability of temporal discrimination during cyclical hormonal change raises interesting questions concerning the age-related sexually-dimorphic decline observed in temporal discrimination. Our findings pave the way for future studies exploring potential pathomechanisms for this age-related deterioration. © 2017 Institute of Physics and Engineering in Medicine.


Mc Govern E.M.,St Vincents University Hospital | Mc Govern E.M.,University College Dublin | Mc Govern E.M.,Trinity Center for Bioengineering | Butler J.S.,Trinity Center for Bioengineering | And 14 more authors.
Physiological Measurement | Year: 2017

The temporal discrimination threshold (TDT) is the shortest time interval at which an individual detects two stimuli to be asynchronous (normal = 30-50 ms). It has been shown to be abnormal in patients with disorders affecting the basal ganglia including adult onset idiopathic focal dystonia (AOIFD). Up to 97% of patients have an abnormal TDT with age- and sex-related penetrance in unaffected relatives, demonstrating an autosomal dominant inheritance pattern. These findings support the use of the TDT as a pre-clinical biomarker for AOIFD. The usual stimulus presentation method involves the presentation of progressively asynchronous stimuli; when three sequential stimuli are reported asynchronous is taken as a participant's TDT. To investigate the robustness of the 'staircase' method of presentation, we introduced a method of randomised presentation order to explore any potential 'learning effect' that may be associated with this existing method. The aim of this study was to investigate differences in temporal discrimination using two methods of stimulus presentation. Thirty healthy volunteers were recruited to the study (mean age 33.73 3.4 years). Visual and tactile TDT testing using a staircase and randomised method of presentation order was carried out in a single session. There was a strong relationship between the staircase and random method for TDT values. This observed consistency between testing methods suggests that the existing experimental approach is a robust method of recording an individual's TDT. In addition, our newly devised randomised paradigm is a reproducible and more efficient method for data acquisition in the clinic setting. However, the two presentation methods yield different absolute TDT results and either of the two methods should be used uniformly in all participants in any one particular study. © 2017 Institute of Physics and Engineering in Medicine.


PubMed | Anglia, The Irish Longitudinal Study on Ageing and., Trinity Center for Bioengineering and Trinity College Dublin
Type: Journal Article | Journal: The journals of gerontology. Series A, Biological sciences and medical sciences | Year: 2014

For single gait tasks, associations have been reported between gait speed and cognitive domains. However, few studies have evaluated if this association is altered in dual gait tasks given gait speed changes with complexity and nature of task. We evaluated relative contributions of specific elements of cognitive function (including sustained attention and processing speed) to dual task gait speed in a nationally representative population of community-dwelling adults over 50 years.Gait speed was obtained using the GaitRite walkway during three gait tasks: single, cognitive (alternate letters), and motor (carrying a filled glass). Linear regression models, adjusted for covariates, were constructed to predict the relative contributions of seven neuropsychological tests to gait speed differences and to investigate gait task effects.The mean age and gait speed of the population (n = 4,431, 55% women) was 62.4 years (SD = 8.2) and 135.85 cm/s (SD = 20.20, single task), respectively. Poorer processing speed, short-term memory, and sustained attention were major cognitive contributors to slower gait speed for all gait tasks. Both dual gait tasks were robust to covariate adjustment and had a significant additional executive function element not found for the single gait task.For community-dwelling older adults processing speed, short-term memory and sustained attention were independently associated with gait speed for all gait tasks. Dual gait tasks were found to highlight specific executive function elements. This result forms a baseline value for dual task gait speed.


Mulcahy L.E.,Trinity Center for Bioengineering | Mulcahy L.E.,Royal College of Surgeons in Ireland | Curtin C.M.,Trinity Center for Bioengineering | Curtin C.M.,Royal College of Surgeons in Ireland | And 13 more authors.
European Cells and Materials | Year: 2015

Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone’s capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis. © 2015, AO Research Institute. All rights reserved.


Levingstone T.J.,Royal College of Surgeons in Ireland | Levingstone T.J.,Trinity Center for Bioengineering | Matsiko A.,Royal College of Surgeons in Ireland | Matsiko A.,Trinity Center for Bioengineering | And 6 more authors.
Acta Biomaterialia | Year: 2014

Cartilage and osteochondral defects pose a significant challenge in orthopedics. Tissue engineering has shown promise as a potential method for the treatment of such defects; however, a long-lasting repair strategy has yet to be realized. This study focuses on the development of a layered construct for osteochondral repair, fabricated through a novel "iterative layering" freeze-drying technique. The process involved repeated steps of layer addition followed by freeze-drying, enabling control over material composition, pore size and substrate stiffness in each region of the construct, while also achieving a seamlessly integrated layer structure. The novel construct developed mimics the inherent gradient structure of healthy osteochondral tissue: a bone layer composed of type I collagen and hydroxyapatite (HA), an intermediate layer composed of type I collagen, type II collagen and HA and a cartilaginous region composed of type I collagen, type II collagen and hyaluronic acid. The material properties were designed to provide the biological cues required to encourage infiltration of host cells from the bone marrow while the biomechanical properties were designed to provide an environment optimized to promote differentiation of these cells towards the required lineage in each region. This novel osteochondral graft was shown to have a seamlessly integrated layer structure, high levels of porosity (>97%), a homogeneous pore structure and a high degree of pore interconnectivity. Moreover, homogeneous cellular distribution throughout the entire construct was evident following in vitro culture, demonstrating the potential of this multi-layered scaffold as an advanced strategy for osteochondral defect repair. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Mulcahy L.E.,Trinity Center for Bioengineering | Mulcahy L.E.,Royal College of Surgeons in Ireland | Taylor D.,Trinity Center for Bioengineering | Lee T.C.,Trinity Center for Bioengineering | And 3 more authors.
Bone | Year: 2011

Bone remodelling is an intricate process encompassing numerous paracrine and autocrine biochemical pathways and mechanical mechanisms. It is responsible for maintaining bone homeostasis, structural integrity and function. The RANKL-RANK-OPG cytokine system is one of the principal mediators in the maintenance of bone cell function and activation of bone remodelling by the Basic Multicellular Unit (BMU) which carries out remodelling. Theories surrounding the initiation of bone remodelling include mechanical loading, fluid flow and microdamage as potential stimuli. This study focused on microdamage. In an in vitro simulated bone environment, gel embedded MLO-Y4 cell networks were subjected to damage in the form of planar, crack-like defects of constant area and varying thickness. The biochemical response was determined by ELISA and luciferase assay. The results showed that RANKL release increased and OPG decreased in a manner which depended on injury size (i.e. thickness) and time following application of injury. The effect of microdamage on cell viability and apoptosis was also evaluated. This work demonstrates that injury alone, in the absence of imposed strain or fluid flow, is sufficient to initiate changes in cytokine concentrations of the type which are known to stimulate bone remodeling. © 2010 Elsevier Inc.


Sheridan W.S.,Trinity College Dublin | Duffy G.P.,Royal College of Surgeons in Ireland | Murphy B.P.,Trinity Center for Bioengineering
International Journal of Nano and Biomaterials | Year: 2012

Tissue engineering small diameter vascular grafts requires excessive culture times to produce an appropriate extracellular matrix (ECM). The use of decellularised exogenous tissue as a scaffold has the potential to overcome this limitation due to the preformed ideal ECM architecture that remains after decellularisation. While this scaffold reduces ECM maturation times cell seeding is difficult due to the high density of decellularised tissue, particularly within the medial layer of the scaffold. In this study, we investigated the possibility of direct injection of vascular cells within decellularised porcine carotid arteries through the use of micro-needles inserted into the medial layer prior to decellularisation. The results indicate that these injection methods are feasible and provide a method for quickly bulk cell seeding decellularised scaffolds. Copyright © 2012 Inderscience Enterprises Ltd.


Killane I.,Trinity Center for Bioengineering | Killane I.,Trinity College Dublin | Donoghue O.A.,Trinity College Dublin | Savva G.M.,Trinity College Dublin | And 5 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2014

Background. For single gait tasks, associations have been reported between gait speed and cognitive domains. However, few studies have evaluated if this association is altered in dual gait tasks given gait speed changes with complexity and nature of task. We evaluated relative contributions of specific elements of cognitive function (including sustained attention and processing speed) to dual task gait speed in a nationally representative population of community-dwelling adults over 50 years. Methods. Gait speed was obtained using the GaitRite walkway during three gait tasks: single, cognitive (alternate letters), and motor (carrying a filled glass). Linear regression models, adjusted for covariates, were constructed to predict the relative contributions of seven neuropsychological tests to gait speed differences and to investigate gait task effects. Results. The mean age and gait speed of the population (n = 4,431, 55% women) was 62.4 years (SD = 8.2) and 135.85 cm/s (SD = 20.20, single task), respectively. Poorer processing speed, short-term memory, and sustained attention were major cognitive contributors to slower gait speed for all gait tasks. Both dual gait tasks were robust to covariate adjustment and had a significant additional executive function element not found for the single gait task. Conclusions. For community-dwelling older adults processing speed, short-term memory and sustained attention were independently associated with gait speed for all gait tasks. Dual gait tasks were found to highlight specific executive function elements. This result forms a baseline value for dual task gait speed. © The Author 2014.


Stops A.J.F.,National University of Ireland | Harrison N.M.,National University of Ireland | Haugh M.G.,Royal College of Surgeons in Ireland | Haugh M.G.,Trinity Center for Bioengineering | And 3 more authors.
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2010

Artificial tissue growth requires cells to proliferate and differentiate within the host scaffold. As cell function is governed by mechano-sensitive selection, tissue type is influenced by the microscopic forces exposed to the cells, which is a product of macroscopically straining the scaffold. Accordingly, the microscopic strain environment within a CG scaffold is offered here. Using μCT to characterise CG scaffold architecture, two high-resolution 3D FE models were used to predict the deformation mechanics. While also providing an analysis of region-specific features, such as relative density, pore diameters and microstructural elastic stability, the deformation patterns afforded strains to be inferred for seeded cells. The results indicate a regional dependence, in terms of architectural and mechanical properties. Specifically, the peripheral regions demonstrated the lowest volume fraction, the highest stress concentrations and the greatest potential for elastic instability. Conversely, the mid-region exhibited the most homogeneous environment. Based on the proviso of mechano-sensitive proliferation and differentiation, the findings suggest cell function will vary between CG scaffold regions. Further work should investigate the possibility of improving the fabrication process in order to deliver a construct in line with the mid-region, or alternatively, isolation of the mid-region may prove beneficial for cell culturing. © 2010 Elsevier Ltd. All rights reserved.


Mealy J.,Trinity Center for Bioengineering | Mealy J.,Trinity College Dublin | O'Kelly K.,Trinity Center for Bioengineering | O'Kelly K.,Trinity College Dublin
Journal of Biomedical Materials Research - Part A | Year: 2015

Increased mesenchymal stem cell (MSC) activity on hydroxyapatite (HA) bone tissue engineering scaffolds will improve their viability in diffusion-based in vivo environments and is therefore highly desirable. This work focused on modulating the sintered HA surface topography with a view to increasing cell activity; this was achieved by varying the sintering temperature of the HA substrates. Cells were cultured on the substrates for periods of up to 19 days and displayed a huge variation in viability. MSC metabolic activity was measured using a resazurin sodium salt assay and revealed that surfaces sintered from 1250 to 1350°C significantly outperformed their lower temperature counterparts from day one (p ≤ 0.05). Surfaces sintered at 1300°C induced 57% more cell activity than the control at day 16. No significant activity was observed on surfaces sintered below 1200°C. It is suggested that this is due to the granular morphology produced at these temperatures providing insufficient contact area for cell attachment. In addition, we propose the average surface wavelength as a more quantitative surface descriptor than those readily found in the literature. The wavelengths of the substrates presented here were highly correlated with cell activity (R2 = 0.9019); with a wavelength of 2.675 μm on the 1300°C surface inducing the highest cell response. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3533-3538, 2015. © 2015 Wiley Periodicals, Inc.

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