CERES :: Browsing by Author "Zioupos, Peter"

Browsing by Author "Zioupos, Peter"

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Open Access
3D printing, the future of cost effective biomechanical testing
(SAFE, 2017-04-06) Franceskides, C.; Arnold, Emily; Horsfall, Ian; Clasper, J.; Tozzi, G.; Zioupos, Peter
Open Access
Age related changes of rib cortical bone matrix and the application to forensicage-at-death estimation
(Nature Publishing Group, 2021-01-22) Bonicelli, Andrea; Zioupos, Peter; Arnold, Emily; Rogers, Keith D.; Xhemali, Bledar; Kranioti, Elena F.
Forensic anthropology includes, amongst other applications, the positive identification of unknown human skeletal remains. The first step in this process is an assessment of the biological profile, that is: sex, age, stature and ancestry. In forensic contexts, age estimation is one of the main challenges in the process of identification. Recently established admissibility criteria are driving researchers towards standardisation of methodological procedures. Despite these changes, experience still plays a central role in anthropological examinations. In order to avoid this issue, age estimation procedures (i) must be presented to the scientific community and published in peer reviewed journals, (ii) accurately explained in terms of procedure and (iii) present clear information about the accuracy of the estimation and possible error rates. In order to fulfil all these requirements, a number of methods based on physiological processes which result in biochemical changes in various tissue structures at the molecular level, such as modifications in DNA-methylation and telomere shortening, racemization of proteins and stable isotopes analysis, have been developed. The current work proposes a new systematic approach in age estimation based on tracing physicochemical and mechanical degeneration of the rib cortical bone matrix. This study used autopsy material from 113 rib specimens. A set of 33 parameters were measured by standard bio-mechanical (nanoindentation and microindentation), physical (TGA/DSC, XRD and FTIR) and histomorphometry (porosity-ImageJ) methods. Stepwise regressions were used to create equations that would produce the best ‘estimates of age at death’ vs real age of the cadavers. Five equations were produced; in the best of cases an equation counting 7 parameters had an R2 = 0.863 and mean absolute error of 4.64 years. The present method meets all the admissibility criteria previously described. Furthermore, the method is experience-independent and as such can be performed without previous expert knowledge of forensic anthropology and human anatomy.
Open Access
Age-related changes in femoral head trabecular microarchitecture
(Buck Institute for Age Research, 2017-10-11) Greenwood, Charlene; Clement, John; Dicken, Anthony; Evans, Paul; Lyburn, Iain Douglas; Martin, Richard M.; Stone, Nick; Zioupos, Peter; Rogers, Keith
Osteoporosis is a prevalent bone condition, characterised by low bone mineral density and increased fracture risk. Currently, the gold standard for identifying osteoporosis and increased fracture risk is through quantification of bone mineral density using dual energy X-ray absorption. However, many studies have shown that bone strength, and consequently the probability of fracture, is a combination of both bone mass and bone ‘quality’ (architecture and material chemistry). Although the microarchitecture of both non-fracture and osteoporotic bone has been previously investigated, many of the osteoporotic studies are constrained by factors such as limited sample number, use of ovariectomised animal models, and lack of male and female discrimination. This study reports significant differences in bone quality with respect to the microarchitecture between fractured and non-fractured human femur specimens. Micro-computed tomography was utilised to investigate the microarchitecture of femoral head trabecular bone from a relatively large cohort of non-fracture and fracture human donors. Various microarchitectural parameters have been determined for both groups, providing an understanding of the differences between fracture and non -fracture material. The microarchitecture of non-fracture and fracture bone tissue is shown to be significantly different for many parameters. Differences between sexes also exist, suggesting differences in remodelling between males and females in the fracture group. The results from this study will, in the future, be applied to develop a fracture model which encompasses bone density, architecture and material chemical properties for both female and male tissues.
Open Access
Age-related trends in the trabecular micro-architecture of the medial clavicle: Is it of use in forensic science?
(Cranfield University, 2020-01-21 15:02) McGivern, Hannah; Greenwood, Charlene; Marquez-Grant, Nicholas; F. Kranioti, Elena; Zioupos, Peter
The mechanical and structural properties of bone are known to change significantly with age. Within forensic and archaeological investigations, the medial end of the clavicle is typically used for estimating the age-at-death of an unknown individual. Although, this region of the skeleton is of interest to forensic and clinical domains, alterations beyond the macro-scale have not been fully explored. For this study, non-destructive micro-computed tomography (µ-CT) was employed to characterise structural alterations to the cancellous bone of the medial clavicle. Fresh human cadaveric specimens (12-59 years) obtained at autopsy were utilised for this study, and were scanned with a voxel size of ~83µm. Morphometric properties were quantified and indicated that the bone volume, connectivity, mineral density and number of trabeculae decreased with age, while the spacing between the trabeculae increased with age. In contrast to other sub-regions of the skeleton, trabecular thickness and degree of anisotropy did not correlate with age, which could suggest that the network is becoming increasing perforated with age rather than exhibiting trabecular thinning. These results are used in the context of deriving a potential protocol for forensic investigations by using this particular and largely unexplored region of the skeleton and provide inspiration for future experiments concerning micro-architectural and small scale changes in other regions of the human skeleton.
Open Access
Age-related trends in the trabecular micro-architecture of the medial clavicle: is it of use in forensic science?
(Frontiers, 2020-01-22) McGivern, Hannah; Greenwood, Charlene; Márquez-Grant, Nicholas; Kranioti, Elena F.; Xhemali, Bledar; Zioupos, Peter
The mechanical and structural properties of bone are known to change significantly with age. Within forensic and archaeological investigations, the medial end of the clavicle is typically used for estimating the age-at-death of an unknown individual. Although, this region of the skeleton is of interest to forensic and clinical domains, alterations beyond the macro-scale have not been fully explored. For this study, non-destructive micro-computed tomography (µ-CT) was employed to characterize structural alterations to the cancellous bone of the medial clavicle. Fresh human cadaveric specimens (12-59 years) obtained at autopsy were utilized for this study, and were scanned with a voxel size of ∼83µm. Morphometric properties were quantified and indicated that the bone volume, connectivity density, mineral density, and number of trabeculae decreased with age, while the spacing between the trabeculae increased with age. In contrast to other sub-regions of the skeleton, trabecular thickness, and degree of anisotropy did not correlate with age. Collectively, this could suggest that the network is becoming increasingly perforated with age rather than exhibiting trabecular thinning. These results are used in the context of deriving a potential protocol for forensic investigations by using this particular and largely unexplored region of the skeleton, and provide inspiration for future experiments concerning micro-architectural and small scale changes in other regions of the human skeleton.
Open Access
Ageing bone fractures: the case of a ductile to brittle transition that shifts with age
(Elsevier, 2019-12-03) Zioupos, Peter; Kirchner, Helmut O. K.; Peterlik, Herwig
Human bone becomes increasingly brittle with ageing. Bones also fracture differently under slow and fast loadings, being ductile and brittle, respectively. The effects of a combination of these two factors have never been examined before. Here we show that cortical bone is most fracture-resistant at the physiologically prevalent intermediate strain rates of 10−3 s−1 to 10−2 s−1 such as they occur in walking or running, slightly weaker at slower quasistatic and much weaker at fast impact loading rates. In young cortical bone (15 years of age) the ductile-to-brittle transition (DBT) occurs at strain rates of 10−2 s−1, in old cortical bone (85 yrs) at speeds lower by a factor of 10 to 40. Other research has shown that the energy required to break bone (per unit of fracture surface) drops as much as 60% between these two ages. Therefore, DBT seems to compound the well-known phenomenon of ‘brittle old bones’. Old bones can only cope with slow movement, young ones with both slow and fast movement. These observed material characteristics of (i) a shift of the DBT and (ii) a reduced energy absorption capacity appear to contribute at least as much to the loss of bone quality as the various quantity based (lowered bone density and mineral content) explanations of the past. They also provide a new powerful paradigm, which allows us to demonstrate mechanically, and uniquely, how human bone becomes increasingly brittle with age.
Open Access
Assessing bone maturity: compositional and mechanical properties of rib cortical bone at different ages
(Elsevier, 2021-11-27) Bonicelli, Andrea; Kranioti, Elena F.; Xhemali, Bledar; Arnold, Emily; Zioupos, Peter
Understanding what maturity entails for bone, when it arrives, and its pre- and post-maturity traits and properties are very important for understanding its evolution and physiology. There is a clear but fine distinction between the chronological age of bone (the age of its donor) and the tissue age of the bone packets it comprises at the microscopic level. Whole bone fragility changes with age due to mass and architecture effects, but so do the properties of bone at the tissue level. Tissue age and tissue-level properties are therefore increasingly attracting a great deal of attention recently. The present study investigated compositional and material changes in the hydroxyapatite crystals, the collagenous phase, changes in bone matrix composition and its nanoindentation properties and their decline with chronological age in later life. The aim was to track the age threshold at which cortical bone arrives at maturity and what happens following that threshold. To do so FTIR, DSC/TGA, XRD, nanoindentation and microindentation were used to investigate rib cortical bone material across a cohort of 86 individuals from one ethnic group with age spanning between 17 and 82 years. Results of this cross-sectional study showed a clear increase in mineral content relative to the organic and water contents across all ages. Furthermore, an increase in crystal size and consequent decrease in strain (coherence length) was detected associated with secondary mineralisation and an increase in carbonate substitution. Overall, we observe a number of modifications which contribute to a typical functional behaviour of bone showing an increase in both indentation modulus and hardness until the age of about 35 after which both of these properties decline gradually and concomitantly to other physicochemical changes and seemingly until the end of one's life.
Open Access
Characterisation of human tissues analogues for ballistic testing
(None - paper only available to conference delegates, 2023-08-30) Appleby-Thomas, Gareth J.; Khan, Irfan Ullah; Painter, Jonathan; Zioupos, Peter; Lordachescu, Alexandra; Hes, Roelof A. G.
Ballistic testing necessarily employs simulant target materials for ethical and fiscal reasons. Current tissue analogues utilised for ballistic testing / research are, however, typically relatively simplistic – such as ballistics soap or gelatin. Consequently, these materials are seldom representative of complex mammalian constructs. In this paper the authors have drawn together core elements of previously published in-house research with the aim of providing insight into potential approaches to create a composite simulant solution. In particular, tissue analogues covering the epidermal, epithelial, connective, muscular and skeletal components are presented. These results highlight the complementary nature of employing a range of tissue simulant materials and, in parallel, the importance – if ballistic testing data is to be truly representative – of fully understanding the nature of the analogues employed.
Open Access
Classification of fracture and non-fracture groups by analysis of coherent X-ray scatter
(Nature Publishing Group, 2016-07-01) Dicken, A. J.; Evans, J. Paul O.; Rogers, Keith; Stone, N.; Greenwood, Charlene; Godber, S. X.; Clement, J. G.; Lyburn, Iain Douglas; Martin, R. M.; Zioupos, Peter
Osteoporotic fractures present a significant social and economic burden, which is set to rise commensurately with the aging population. Greater understanding of the physicochemical differences between osteoporotic and normal conditions will facilitate the development of diagnostic technologies with increased performance and treatments with increased efficacy. Using coherent X-ray scattering we have evaluated a population of 108 ex vivo human bone samples comprised of non-fracture and fracture groups. Principal component fed linear discriminant analysis was used to develop a classification model to discern each condition resulting in a sensitivity and specificity of 93% and 91%, respectively. Evaluating the coherent X-ray scatter differences from each condition supports the hypothesis that a causal physicochemical change has occurred in the fracture group. This work is a critical step along the path towards developing an in vivo diagnostic tool for fracture risk prediction.
Open Access
Data for PONE-D-16-41391 'Age at death' method by Bonicelli et al 2017
(Cranfield University, 2017-05-22 08:31) Zioupos, Peter; Bonicelli, Andrea; Elena Kranioti, Dr
Data underpinning the article in PLOS ONE: "Rib biomechanical properties exhibit diagnostic potential for accurate ageing in forensic investigations" by: Andrea Bonicelli 1,2 , Bledar Xhemali 3 , Elena F. Kranioti 1,4, Peter Zioupos 2
Open Access
Data for the article “Localized tissue mineralization regulated by bone remodelling: a computational approach”
(Cranfield University, 2017-05-19 11:52) Zioupos, Peter; José Manuel García Aznar, Professor; Oscar Decco, Professor; Marcelo Berli, Dr; Carlos Borau, Dr; Adams, George; Richard Cook, Dr
Data for the PLOS ONE article: “Localized tissue mineralization regulated by bone remodelling: a computational approach”
Open Access
Data supporting: 'Association between nanoscale strains and tissue level nanoindentation properties in age-related hip-fractures'
(Cranfield University, 2023-01-03 15:26) Bonicelli, Andrea; P Cobb, Justin; R Boughton, Oliver; Hansen, Ulrich; Abel, Richard; Zioupos, Peter
Measurement of the properties of bone as a material can happen in various length scales in its hierarchical and composite structure. The aim of this study was to test the tissue level properties of clinically-relevant human bone samples which were collected from donors belonging to three groups: ageing donors who suffered no fractures (Control); untreated fracture patients (Fx-Untreated) and patient who experienced hip fracture despite being treated with bisphosphonates (Fx-BisTreated).
Open Access
Data supporting: 'Microarchitecture and morphology of bone tissue over a wide range of BV/TV assessed by micro-computed tomography and three different threshold backgrounds'
(Cranfield University, 2022-09-01 15:36) Zioupos, Peter; Adams, George; B. Cook, Richard; Hutchinson, John
Data for the published paper entitled: "Microarchitecture and morphology of bone tissue over a wide range of BV/TV assessed by micro-computed tomography and three different threshold backgrounds"
Open Access
Determining 'age at death' for forensic purposes using human bone by a laboratory-based biomechanical analytical method
(Elsevier, 2013-10-31) Zioupos, Peter; Williams, A.; Christodoulou, G.; Giles, R.
Determination of age-at-death (AAD) is an important and frequent requirement in contemporary forensic science and in the reconstruction of past populations and societies from their remains. Its estimation is relatively straightforward and accurate (±3 yr) for immature skeletons by using morphological features and reference tables within the context of forensic anthropology. However, after skeletal maturity (>35 yr) estimates become inaccurate, particularly in the legal context. In line with the general migration of all the forensic sciences from reliance upon empirical criteria to those which are more evidence-based, AAD determination should rely more-and-more upon more quantitative methods. We explore here whether well-known changes in the biomechanical properties of bone and the properties of bone matrix, which have been seen to change with age even after skeletal maturity in a traceable manner, can be used to provide a reliable estimate of AAD. This method charts a combination of physical characteristics some of which are measured at a macroscopic level (wet & dry apparent density, porosity, organic/mineral/water fractions, collagen thermal degradation properties, ash content) and others at the microscopic level (Ca/P ratios, osteonal and matrix microhardness, image analysis of sections). This method produced successful age estimates on a cohort of 12 donors of age 53–85 yr (7 male, 5 female), where the age of the individual could be approximated within less than ±1 yr. This represents a vastly improved level of accuracy than currently extant age estimation techniques. It also presents: (1) a greater level of reliability and objectivity as the results are not dependent on the experience and expertise of the observer, as is so often the case in forensic skeletal age estimation methods; (2) it is purely laboratory-based analytical technique which can be carried out by someone with technical skills and not the specialised forensic anthropology experience; (3) it can be applied worldwide following stringent laboratory protocols. As such, this technique contributes significantly to improving age estimation and therefore identification methods for forensic and other purposes.
Open Access
Determining ‘Age at Death’: A new multidisciplinary laboratory method based on ribs
(European Society of Biomechanics, 2016-07-10) Bonicelli, A.; Zioupos, Peter; Xhemali, B.; Kranioti, E. F.
Current protocol in determining if a patient is osteoporotic and their fracture risk is based on dual energy X-ray absorptiometry (DXA). DXA gives an indication of their bone mineral density (BMD) which is the product of both the porosity and density of the mineralized bone tissue; this is usually taken at the hip. The DXA results are assessed using the fracture risk assessment tool as recommended by the World Health Organization. While this provides valuable data on a person’s fracture risk advancements in medical imagining technology enables development of more robust and accurate risk assessment tools. In order to develop such tools in vitro analysis of bone is required to assess the morphological properties of bone osteoporotic bone tissue and how these pertain to the fracture toughness (Kcmax) of the tissue.
Open Access
The diabetes epidemic in the South Pacific: a pilot study utilising hand grip strength in Tonga
(Lupine, 2019-02-18) Zioupos, Maria-Eleni; Takai, Joseph; Ahmad, Mehtab; Zioupos, Peter
Background: Hand-grip strength (HGS) has been shown recently to help in predicting disease outcomes and assessing health risk, particularly in cardiovascular and metabolic disease. Studies confirming its link to diabetes (T2DM) suggest there is potential for its use as simple screening tool. This study examined this possibility in a developing-world population, in a cohort of Tongan diabetics. Methods: HGS was measured in a randomly selected cohort of patients, comprising in total 149 patients, of which 91 with and 58 without T2DM. Other measurements recorded included patient demographics, blood pressure and date of diabetes diagnosis. Results: HGS was found to reduce significantly with age in all groups and it also related to BMI in males. Binary logistics regression models were produced using ‘HGS,’ ‘Age’ and ‘BMI’ which had a sensitivity of 82-84% (M/F) and specificity of 50-57%. Conclusions: This study uses one of the well-known effects and complications of T2DM, affected hand grip strength of sufferers, as a parameter in a ‘tool’ to predict the presence of the disease showing very good sensitivity. Further research is needed into the more general utility of the tool, while further work may help identify among the diagnosed those who would benefit from specialist treatment.
Open Access
Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant induced arthritis rat model
(Oxford University Press, 2017-08-10) Vidal, Bruno; Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês P.; da Glória, Vânia G.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E.
Rheumatoid arthritis (RA) causes immune mediated local and systemic bone damage. Objectives - The main goal of this work was to analyze, how treatment intervention with tofacitinib prevents the early disturbances on bone structure and mechanics in adjuvant induced arthritis rat model. This is the first study to access the impact of tofacitinib on the systemic bone effects of inflammation. Methods - Fifty Wistar adjuvant-induced arthritis (AIA) rats were randomly housed in experimental groups, as follows: non-arthritic healthy group (N=20), arthritic non-treated (N=20) and 10 animals under tofacitinib treatment. Rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation analysis. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. Results - At tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and 3-point bending tests revealed that tofacitinib did not revert the effects of arthritis on cortical and trabecular bone structure and on mechanical properties. Conclusion - Possible reasons for these observations might be related with the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or with kinetics of its bone effects that might need longer exposure.
Open Access
Effects of tofacitinib in early arthritis-induced bone loss in an adjuvant-induced arthritis rat model
(Oxford University Press, 2017-08-10) Vidal, Bruno; Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês P.; da Glória, Vânia G.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João Eurico
Objectives: The main goal of this work was to analyse how treatment intervention with tofacitinib prevents the early disturbances of bone structure and mechanics in the rat model of adjuvant-induced arthritis. This is the first study to access the impact of tofacitinib on the skeletal bone effects of inflammation. Methods: Fifty Wistar rats with adjuvant-induced arthritis were randomly housed in experimental groups, as follows: non-arthritic healthy group (n = 20); arthritic non-treated group (n = 20); and 10 animals undergoing tofacitinib treatment. Rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for comparison. After 22 days of disease progression, rats were killed and bone samples collected for histology, micro-CT, three-point bending and nanoindentation analysis. Blood samples were also collected for quantification of bone turnover markers and systemic cytokines. Results. At the tissue level, measured by nanoindentation, tofacitinib increased bone cortical and trabecular hardness. However, micro-CT and three-point bending tests revealed that tofacitinib did not reverse the effects of arthritis on the cortical and trabecular bone structure and on mechanical properties. Conclusion: Possible reasons for these observations might be related to the mechanism of action of tofacitinib, which leads to direct interactions with bone metabolism, and/or to the kinetics of its bone effects, which might need longer exposure.
Open Access
Effects of μCT and FE resolution in expressing anisotropic properties in vertebral cancellous bone
(Institute of Naval Medicine, 2016-09-15) Shanker, Tobias; Franceskides, Constantinos; Gibson, Michael C.; Clasper, J.; Adams, George; Zioupos, Peter
With an aging population lower back pain is a growing concern amongst many people. Recent developments in FE have made possible the simulation of complex geometries, such as trabecular bone. Most current techniques homogenise vertebrae into solids with averaged material properties. This is undesirable as analysis on the effects within trabecular tissue is impossible. As vertebral tissue is highly anisotropic this study investigates the effects on anisotropy when the mesh resolution and orientation are varied. Trabecular cubes were taken from a human donor at different orientations around the medial-lateral axis (0°, 45°, 90°) and tested in all three axes. Prior to testing they were CT scanned (X-Tek), reconstructed (CTPro) for and meshed (ScanlP). The full size scans were linearly downsampled to 32pm, 50pm, 64pm, 128pm and 256pm. Using a power-law based on material properties in the literature (E=15GPa, p=1800 g/cm3 and v=0.3) each mesh was quasi-statically compressed in all three directions. Our finite-element analysis shows good agreement with the experimental results, showing that a pixel resolution of 64pm is good for preserving anisotropy in vertebral bone. This model was further validated against the other models at different orientations also showing a good agreement with the experimental results.
Open Access
Estimation of local anisotropy of plexiform bone: Comparison between depth sensing micro-indentation and Reference Point Indentation
(Elsevier, 2015-10-09) Dall'Ara, E.; Grabowski, P.; Zioupos, Peter; Viceconti, M.
The recently developed Reference Point Indentation (RPI) allows the measurements of bone properties at the tissue level in vivo. The goal of this study was to compare the local anisotropic behaviour of bovine plexiform bone measured with depth sensing micro-indentation tests and with RPI. Fifteen plexiform bone specimens were extracted from a bovine femur and polished down to 0.05 µm alumina paste for indentations along the axial, radial and circumferential directions (N=5 per group). Twenty-four micro-indentations (2.5 µm in depth, 10% of them were excluded for testing problems) and four RPI-indentations (~50 µm in depth) were performed on each sample. The local indentation modulus Eind was found to be highest for the axial direction (24.3±2.5 GPa) compared to the one for the circumferential indentations (19% less stiff) and for the radial direction (30% less stiff). RPI measurements were also found to be dependent on indentation direction (p<0.001) with the exception of the Indentation Distance Increase (IDI) (p=0.173). In particular, the unloading slope US1 followed similar trends compared to the Eind: 0.47±0.03 N/µm for axial, 11% lower for circumferential and 17% lower for radial. Significant correlations were found between US1 and Eind (p=0.001; R2=0.58), while no significant relationship was found between IDI and any of the micro-indentation measurements (p>0.157). In conclusion some of the RPI measurements can provide information about local anisotropy but IDI cannot. Moreover, there is a linear relationship between most local mechanical properties measured with RPI and with micro-indentations, but IDI does not correlate with any micro-indentation measurements

Browsing by Author "Zioupos, Peter"

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