K. Elizabeth Tanner
University of Glasgow
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Featured researches published by K. Elizabeth Tanner.
Bone | 2010
Carmen Huesa; Manisha C. Yadav; Mikko Finnilä; Simon R. Goodyear; Simon P. Robins; K. Elizabeth Tanner; Richard M. Aspden; José Luis Millán; Colin Farquharson
Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1(-/-) mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1(-/-) mice did not fracture during 3-point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1(-/-) tibiae were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1(-/-) tibia. The altered dihydroxylysinonorleucine/hydroxylysinonorleucine and pyridinoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase-1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type I collagen, were both increased in Phospho1(-/-) mice and this we associated with increased bone remodeling during fracture repair or an attempt to remodel a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1(-/-) bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an undermineralized yet active bone.
Journal of Biomaterials Applications | 2011
Antonio Gloria; Roberto De Santis; Luigi Ambrosio; Filippo Causa; K. Elizabeth Tanner
Spinal disease due to intervertebral disc degeneration represents a serious medical problem which affects many people worldwide. Disc arthroplasty may be considered the future ‘‘gold standard’’ of back pain treatment, even if problems related to available disc prostheses are considered. Hence, the aim of the present study was to improve the artificial disc technology by proposing the engineering of a pilot-scale device production process for a total multi-component intervertebral disc prosthesis. The device is made up of a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibers as annulus/nucleus substitute, and two hydroxyapatite-reinforced polyethylene composite (HAPEX TM) endplates in order to anchor the multi-component device to the vertebral bodies. Static and dynamic—mechanical characterization show appropriate mechanical behavior. An example of engineering of a suitable pilot-scale device production process is also proposed in order to manufacture custom made implants.
Journal of the Royal Society Interface | 2014
Susan C. Fitzer; Wenzhong Zhu; K. Elizabeth Tanner; Vernon R. Phoenix; Nicholas A. Kamenos; Maggie Cusack
Ocean acidification (OA) and the resultant changing carbonate saturation states is threatening the formation of calcium carbonate shells and exoskeletons of marine organisms. The production of biominerals in such organisms relies on the availability of carbonate and the ability of the organism to biomineralize in changing environments. To understand how biomineralizers will respond to OA the common blue mussel, Mytilus edulis, was cultured at projected levels of pCO2 (380, 550, 750, 1000 µatm) and increased temperatures (ambient, ambient plus 2°C). Nanoindentation (a single mussel shell) and microhardness testing were used to assess the material properties of the shells. Youngs modulus (E), hardness (H) and toughness (KIC) were measured in mussel shells grown in multiple stressor conditions. OA caused mussels to produce shell calcite that is stiffer (higher modulus of elasticity) and harder than shells grown in control conditions. The outer shell (calcite) is more brittle in OA conditions while the inner shell (aragonite) is softer and less stiff in shells grown under OA conditions. Combining increasing ocean pCO2 and temperatures as projected for future global ocean appears to reduce the impact of increasing pCO2 on the material properties of the mussel shell. OA may cause changes in shell material properties that could prove problematic under predation scenarios for the mussels; however, this may be partially mitigated by increasing temperature.
European Spine Journal | 2012
Jérôme Noailly; Luigi Ambrosio; K. Elizabeth Tanner; Josep A. Planell; Damien Lacroix
When the intervertebral disc is removed to relieve chronic pain, subsequent segment stabilization should restore the functional mechanics of the native disc. Because of partially constrained motions and the lack of intrinsic rotational stiffness ball-on-socket implants present many disadvantages. Composite disc substitutes mimicking healthy disc structures should be able to assume the role expected for a disc substitute with fewer restrictions than ball-on-socket implants. A biomimetic composite disc prototype including artificial nucleus fibre-reinforced annulus and endplates was modelled as an L4–L5 disc substitute within a L3–L5 lumbar spine finite element model. Different device updates, i.e. changes of material properties fibre distributions and volume fractions and nucleus placements were proposed. Load- and displacement-controlled rotations were simulated with and without body weight applied. The original prototype reduced greatly the flexibility of the treated segment with significant adjacent level effects under displacement-controlled or hybrid rotations. Device updates allowed restoring large part of the global axial and sagittal rotational flexibility predicted with the intact model. Material properties played a major role, but some other updates were identified to potentially tune the device behaviour against specific motions. All device versions altered the coupled intersegmental shear deformations affecting facet joint contact through contact area displacements. Loads in the bony endplates adjacent to the implants increased as the implant stiffness decreased but did not appear to be a strong limitation for the implant biomechanical and mechanobiological functionality. In conclusion, numerical results given by biomimetic composite disc substitutes were encouraging with greater potential than that offered by ball-on-socket implants.
Human Molecular Genetics | 2016
Paul D. Ross; Jacky Guy; Jim Selfridge; Bushra Kamal; Noha G. Bahey; K. Elizabeth Tanner; Thomas H. Gillingwater; Ross A. Jones; Christopher M. Loughrey; Charlotte S. McCarroll; Mark E.S. Bailey; Adrian Bird; Stuart Cobb
Abstract Rett syndrome (RTT) is a severe genetic disorder resulting from mutations in the X-linked MECP2 gene. MeCP2 protein is highly expressed in the nervous system and deficiency in the mouse central nervous system alone recapitulates many features of the disorder. This suggests that RTT is primarily a neurological disorder, although the protein is reportedly widely expressed throughout the body. To determine whether aspects of the RTT phenotype that originate in non-neuronal tissues might have been overlooked, we generated mice in which Mecp2 remains at near normal levels in the nervous system, but is severely depleted elsewhere. Comparison of these mice with wild type and globally MeCP2-deficient mice showed that the majority of RTT-associated behavioural, sensorimotor, gait and autonomic (respiratory and cardiac) phenotypes are absent. Specific peripheral phenotypes were observed, however, most notably hypo-activity, exercise fatigue and bone abnormalities. Our results confirm that the brain should be the primary target for potential RTT therapies, but also strongly suggest that some less extreme but clinically significant aspects of the disorder arise independently of defects in the nervous system.
Bone | 2015
Bushra Kamal; David Russell; Anthony P. Payne; Diogo Constante; K. Elizabeth Tanner; Hanna Isaksson; Neashan Mathavan; Stuart Cobb
Rett syndrome (RTT) is an X-linked genetic disorder and a major cause of intellectual disability in girls. Mutations in the methyl-CpG binding protein 2 (MECP2) gene are the primary cause of the disorder. Despite the dominant neurological phenotypes, MECP2 is expressed ubiquitously throughout the body and a number of peripheral phenotypes such as scoliosis, reduced bone mineral density and skeletal fractures are also common and important clinical features of the disorder. In order to explore whether MeCP2 protein deficiency results in altered structural and functional properties of bone and to test the potential reversibility of any defects, we have conducted a series of histological, imaging and biomechanical tests of bone in a functional knockout mouse model of RTT. Both hemizygous Mecp2stop/y male mice in which Mecp2 is silenced in all cells and female Mecp2stop/+ mice in which Mecp2 is silenced in ~ 50% of cells as a consequence of random X-chromosome inactivation, revealed significant reductions in cortical bone stiffness, microhardness and tensile modulus. Microstructural analysis also revealed alterations in both cortical and cancellous femoral bone between wild-type and MeCP2-deficient mice. Furthermore, unsilencing of Mecp2 in adult mice cre-mediated stop cassette deletion resulted in a restoration of biomechanical properties (stiffness, microhardness) towards wild-type levels. These results show that MeCP2-deficiency results in overt, but potentially reversible, alterations in the biomechanical integrity of bone and highlights the importance of targeting skeletal phenotypes in considering the development of pharmacological and gene-based therapies.
Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine | 2014
M.K. Gislason; S. Coupaud; Keisuke Sasagawa; Yuji Tanabe; Mariel Purcell; David B. Allan; K. Elizabeth Tanner
The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions – compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.
Journal of Tissue Engineering | 2013
Randa Alfotawi; Kurt Busuttil Naudi; Matthew J. Dalby; K. Elizabeth Tanner; Jeremy McMahon; Ashraf Ayoub
Cements for maxillofacial reconstruction of jaw defects through calcification of rotated muscle have been tested. The objective of this study was to investigate the visibility of loading of two types of commercially available cements, Cerament™ Spine Support and Cerament Bone Void Filler with mesenchymal cells and cytokines (bone morphogenetic protein) to act as a biomimetic scaffolding for future clinical application. Determination of basic biocompatibility (cell viability) using methyl thiazolyl tetrazolium and live/dead assay was carried out using MG-63 cells at various time points. Next, in order to inform potential subsequent in vivo experiments, a collagen tissue mimic was used for characterization of rabbit mesenchymal stromal cells using immunofluorescent cytoskeleton staining, and simultaneous and then sequential injection of Cerament Spine Support cement and cells into collagen gels. Results indicated that Cerament Spine Support was more biocompatible and that sequential injection of cement and then rabbit mesenchymal stromal cells into the tissue mimics is an optimal approach for clinical applications.
Materials Science and Engineering: C | 2017
Isaiah Adekanmbi; Christopher Z. Mosher; Helen H. Lu; Mathis O. Riehle; Haytham Kubba; K. Elizabeth Tanner
Biodegradable magnesium alloys including AZ31 are exciting candidates for temporary implants as they eliminate the requirement for surgical removal, yet have higher mechanical properties than degradable polymers. However, the very long term mechanical properties and degradation of these alloys have not been fully characterized. The tensile, bending and corrosion behaviour of biodegradable AZ31 Mg alloy specimens have been investigated for up to 9months in vitro in phosphate buffered saline (PBS). Small AZ31 Mg specimens showed a significant drop in bend yield strength and modulus after 3months in vitro degradation and an average mass loss of 6.1%. Larger dumbbell specimens showed significant drops in tensile strength from 251.96±3.53MPa to 73.5±20.2MPa and to 6.43±0.9MPa and in modulus from 47.8±5.6GPa to 25.01±3.4GPa and 2.36±0.89GPa after 3 and 9months respectively. These reductions were accompanied by an average mass loss of 18.3% in 9months. Degradation rate for the small and large specimens followed similar profiles with immersion time, with peak degradation rates of 0.1747gm-2h-1 and 0.0881gm-2h-1, and average rates of 0.1038gm-2h-1 and 0.0397gm-2h-1 respectively. SEM fractography and polished specimen cross-sections revealed corrosion pits, cracks and corrosion induced defects. These data indicate the potential of AZ31 Mg for use in implants that require medium term degradation with load bearing mechanical properties.
PLOS ONE | 2014
Randa Al-Fotawei; Ashraf Ayoub; Neil Heath; Kurt Busuttil Naudi; K. Elizabeth Tanner; Matthew J. Dalby; Jeremy McMahon
This study presents a comprehensive radiographic evaluation of bone regeneration within a pedicled muscle flap for the reconstruction of critical size mandibular defect. The surgical defect (20 mm×15 mm) was created in the mandible of ten experimental rabbits. The masseter muscle was adapted to fill the surgical defect, a combination of calcium sulphate/hydroxyapatite cement (CERAMENT™ |SPINE SUPPORT), BMP-7 and rabbit mesenchymal stromal cells (rMSCs) was injected inside the muscle tissue. Radiographic assessment was carried out on the day of surgery and at 4, 8, and 12 weeks postoperatively. At 12 weeks, the animals were sacrificed and cone beam computerized tomography (CBCT) scanning and micro-computed tomography (µ-CT) were carried out. Clinically, a clear layer of bone tissue was identified closely adherent to the border of the surgical defect. Sporadic radio-opaque areas within the surgical defect were detected radiographically. In comparison with the opposite non operated control side, the estimated quantitative scoring of the radio-opacity was 46.6% ±15, the mean volume of the radio-opaque areas was 63.4% ±20. Areas of a bone density higher than that of the mandibular bone (+35% ±25%) were detected at the borders of the surgical defect. The micro-CT analysis revealed thinner trabeculae of the regenerated bone with a more condensed trabecular pattern than the surrounding native bone. These findings suggest a rapid deposition rate of the mineralised tissue and an active remodelling process of the newly regenerated bone within the muscle flap. The novel surgical model of this study has potential clinical application; the assessment of bone regeneration using the presented radiolographic protocol is descriptive and comprehensive. The findings of this research confirm the remarkable potential of local muscle flaps as local bioreactors to induce bone formation for reconstruction of maxillofacial bony defects.