| 1. |
- Grassi, Lorenzo, et al.
(author)
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Elucidating failure mechanisms in human femurs during a fall to the side using bilateral digital image correlation
- 2020
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In: Journal of Biomechanics. - : Elsevier BV. - 0021-9290. ; 106
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Journal article (peer-reviewed)abstract
- An improved understanding of the mechanical properties of human femurs is a milestone towards a more accurate assessment of fracture risk. Digital image correlation (DIC) has recently been adopted to provide full-field strain measurements during mechanical testing of femurs. However, it has typically been used to measure strains on the anterior side of the femur, whereas in both single-leg-stance and sideways fall loading conditions, the highest deformations result on the medial and lateral sides of the femoral neck. The goal of this study was to measure full-field deformations simultaneously on the medial and lateral side of the femoral neck in a configuration resembling a fall to the side. Twelve female cadaver femurs were prepared for DIC measurements and tested in sideways fall at 5 mm/s displacement rate. Two pairs of cameras recorded the medial and lateral side of the femoral neck, and deformations were calculated using DIC. The samples exhibited a two-stage failure: first, a compressive collapse on the superolateral side of the femoral neck in conjunction with peak force, followed by complete femoral neck fracture at the force drop following the post-elastic phase. DIC measurements corroborated this observation by reporting no tensile strains above yield limit for the medial side of the neck up to peak force. DIC measurements registered onto the bone micro-architecture showed strain localizations in proximity of cortical pores due to, for instance, blood vessels. This could explain previously reported discrepancies between simulations and experiments in regions rich with large pores, like the superolateral femoral neck.
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| 2. |
- Grassi, Lorenzo, et al.
(author)
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How accurately can subject-specific finite element models predict strains and strength of human femora? Investigation using full-field measurements
- 2016
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In: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 49:5, s. 802-806
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Journal article (peer-reviewed)abstract
- Subject-specific finite element models have been proposed as a tool to improve fracture risk assessment in individuals. A thorough laboratory validation against experimental data is required before introducing such models in clinical practice. Results from digital image correlation can provide full-field strain distribution over the specimen surface during in vitro test, instead of at a few pre-defined locations as with strain gauges. The aim of this study was to validate finite element models of human femora against experimental data from three cadaver femora, both in terms of femoral strength and of the full-field strain distribution collected with digital image correlation. The results showed a high accuracy between predicted and measured principal strains (R2=0.93, RMSE=10%, 1600 validated data points per specimen). Femoral strength was predicted using a rate dependent material model with specific strain limit values for yield and failure. This provided an accurate prediction (<2% error) for two out of three specimens. In the third specimen, an accidental change in the boundary conditions occurred during the experiment, which compromised the femoral strength validation. The achieved strain accuracy was comparable to that obtained in state-of-the-art studies which validated their prediction accuracy against 10–16 strain gauge measurements. Fracture force was accurately predicted, with the predicted failure location being very close to the experimental fracture rim. Despite the low sample size and the single loading condition tested, the present combined numerical-experimental method showed that finite element models can predict femoral strength by providing a thorough description of the local bone mechanical response.
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| 3. |
- Mononen, Mika E, et al.
(author)
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A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative.
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group's joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R(2) = 0.95, p < 0.05; experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0-2 years, p < 0.001) was followed by a slow or negligible degeneration (2-4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis.
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| 4. |
- Notermans, Thomas, et al.
(author)
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Understanding how reduced loading affects Achilles tendon mechanical properties using a fibre-reinforced poro-visco-hyper-elastic model
- 2019
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In: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 96, s. 301-309
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Journal article (peer-reviewed)abstract
- Understanding tendon mechanobiology is important for gaining insight into the development of tendon pathology and subsequent repair processes. The aim of this study was to investigate how experimentally observed mechanobiological adaptation of rat Achilles tendons translate to changes in constitutive mechanical properties and biomechanical behavior. In addition, we assessed the ability of the model to simulate tendon creep and stress-relaxation. A three dimensional finite element framework of rat Achilles tendon was implemented with a fibre-reinforced poro-visco-hyper-elastic constitutive model. Stress-relaxation and creep data from Achilles tendons of Sprague Dawley rats that had been subjected to both daily loading and a period of reduced loading were used to determine the constitutive properties of the tendons. Our results showed that the constitutive model captures creep and stress-relaxation data from rat Achilles tendons for both loaded and unloaded tendons with good accuracy (normalized root mean square error between model and experimental data were 0.010–0.027). Only when the model parameters were fitted to data from both mechanical tests simultaneously, were we able to also capture similar increase in elastic energy (increased stiffness)and decreased viscoelasticity in response to unloading, as was reported experimentally. Our study is the first to show that experimentally observed mechanobiological changes in tendon biomechanics, such as stiffness and viscoelasticity, can be designated to mechanical quantities in a constitutive model. Further investigation in this direction has potential to discriminate tissue components responsible for specific biomechanical response, and enable targeted treatment strategies for tendon health.
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| 5. |
- Pierantoni, Maria, et al.
(author)
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Muscular loading affects the 3D structure of both the mineralized rudiment and growth plate at early stages of bone formation
- 2021
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In: Bone. - : Elsevier BV. - 8756-3282. ; 145
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Journal article (peer-reviewed)abstract
- Fetal immobilization affects skeletal development and can lead to severe malformations. Still, how mechanical load affects embryonic bone formation is not fully elucidated. This study combines mechanobiology, image analysis and developmental biology, to investigate the structural effects of muscular loading on embryonic long bones. We present a novel approach involving a semi-automatic workflow, to study the spatial and temporal evolutions of both hard and soft tissues in 3D without any contrast agent at micrometrical resolution. Using high-resolution phase-contrast-enhanced X-ray synchrotron microtomography, we compare the humeri of Splotch-delayed embryonic mice lacking skeletal muscles with healthy littermates. The effects of skeletal muscles on bone formation was studied from the first stages of mineral deposition (Theiler Stages 23 and 24) to just before birth (Theiler Stage 27). The results show that muscle activity affects both growth plate and mineralized regions, especially during early embryonic development. When skeletal muscles were absent, there was reduced mineralization, altered tuberosity size and location, and, at early embryonic stages, decreased chondrocyte density, size and elongation compared to littermate controls. The proposed workflow enhances our understanding of mechanobiology of early bone formation and could be implemented for the study of other complex biological tissues.
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| 6. |
- Dejea, Hector, et al.
(author)
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Multi-scale characterization of the spatio-temporal interplay between elemental composition, mineral deposition and remodelling in bone fracture healing
- 2023
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In: Acta Biomaterialia. - 1742-7061. ; 167, s. 135-146
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Journal article (peer-reviewed)abstract
- Bone mineralization involves a complex orchestration of physico-chemical responses from the organism. Despite extensive studies, the detailed mechanisms of mineralization remain to be elucidated. This study aims to characterize bone mineralization using an in-vivo long bone fracture healing model in the rat. The spatio-temporal distribution of relevant elements was correlated to the deposition and maturation of hydroxyapatite and the presence of matrix remodeling compounds (MMP-13). Multi-scale measurements indicated that (i) zinc is required for both the initial mineral deposition and resorption processes during mature mineral remodeling; (ii) Zinc and MMP-13 show similar spatio-temporal trends during early mineralization; (iii) Iron acts locally and in coordination with zinc during mineralization, thus indicating novel evidence of the time-events and inter-play between the elements. These findings improve the understanding of bone mineralization by explaining the link between the different constituents of this process throughout the healing time.
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| 7. |
- Fågelberg, Emil, et al.
(author)
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Surgical widening of a stress fracture decreases local strains sufficiently to enable healing in a computational model
- 2015
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In: International Biomechanics. - : Informa UK Limited. - 2333-5432. ; 2:1, s. 12-21
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Journal article (peer-reviewed)abstract
- Stress fractures at the tibial diaphysis are prone to delayed union. We hypothesized that the interfragmentary strains in the gap tissue are of magnitudes that prohibit bone formation and healing. If so, a rational treatment would be to widen the fracture gap in order to decrease the strains. This could be achieved by replacing part of the fracture crack with a wide drilled hole. This study analyzes the biomechanical effects of this potential treatment through computational modeling. Poroelastic finite element models of an intact tibia, a tibia with a stress fracture, and a tibia with a drilled stress fracture were developed from clinical CT images. Loads corresponding to gait and stair climbing were simulated. Stresses, strains, and fluid velocities were evaluated for the bone in the tibia, and for the hypothetical soft tissue that fills the stress fracture. A minor decrease in the overall tibial stiffness (<9.9%) was noted as a result of drilling. The models predicted large interfragmentary strains in the soft gap tissue (max 35%) before drilling, which decreased substantially (<1%) after drilling. Thus, when comparing to current mechanobiological tissue differentiation theories, the authors believe that fracture gap widening by drilling a hole might facilitate healing of stress fractures.
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| 8. |
- Khayyeri, Hanifeh, et al.
(author)
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Corroboration of computational models for mechanoregulated stem cell differentiation
- 2015
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In: Computer Methods in Biomechanics and Biomedical Engineering. - : Informa UK Limited. - 1025-5842 .- 1476-8259. ; 18:1, s. 15-23
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Journal article (peer-reviewed)abstract
- Do computational models contribute to progress in mechanobiology? Jacobs and Kelly (in Advances on Modelling in Tissue Engineering, p. 1–14, 2011) suggest that they do, but at the same time propose a limitation in the form of the ‘paradox of validation’, whereby the information needed to validate mechanoregulation theories obviates the need for them in the first place. In this article, the corroboration of theories describing mechanoregulation of tissue differentiation is reviewed. Considering the falsifiability of computational models derived using the theories as a measure of their predictive power, it is shown that the predictive power of some theories is poor and that models based on these theories fall into the ‘paradox of validation’. Week theories for any phenomenon would succumb to such a paradox. We argue that mechanobiology needs theories that can have more potentially falsifying experiments and that perhaps the discipline does suffer from theories that are a priori designed to minimise falsifiability. However, several theories do have predictive power beyond the data used to validate them, so a paradox of validation should disappear as the subject develops.
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| 9. |
- Movérare-Skrtic, Sofia, et al.
(author)
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Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.
- 2014
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 20:11, s. 1279-88
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Journal article (peer-reviewed)abstract
- The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both canonical and noncanonical. Conditional Wnt16 inactivation revealed that osteoblast-lineage cells are the principal source of WNT16, and its targeted deletion in osteoblasts increases fracture susceptibility. Thus, osteoblast-derived WNT16 is a previously unreported key regulator of osteoclastogenesis and fracture susceptibility. These findings open new avenues for the specific prevention or treatment of nonvertebral fractures, a substantial unmet medical need.
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| 10. |
- Ojanen, X, et al.
(author)
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Relationships between tissue composition and viscoelastic properties in human trabecular bone.
- 2015
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In: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 48:2, s. 269-275
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Journal article (peer-reviewed)abstract
- Trabecular bone is a metabolically active tissue with a high surface to volume ratio. It exhibits viscoelastic properties that may change during aging. Changes in bone properties due to altered metabolism are sensitively revealed in trabecular bone. However, the relationships between material composition and viscoelastic properties of bone, and their changes during aging have not yet been elucidated. In this study, trabecular bone samples from the femoral neck of male cadavers (n=21) aged 17-82 years were collected and the tissue level composition and its associations with the tissue viscoelastic properties were evaluated by using Raman microspectroscopy and nanoindentation, respectively. For composition, collagen content, mineralization, carbonate substitution and mineral crystallinity were evaluated. The calculated mechanical properties included reduced modulus (Er), hardness (H) and the creep parameters (E1, E2, η1and η2), as obtained by fitting the experimental data to the Burgers model. The results indicated that the creep parameters, E1, E2, η1and η2, were linearly correlated with mineral crystallinity (r=0.769-0.924, p<0.001). Creep time constant (η2/E2) tended to increase with crystallinity (r=0.422, p=0.057). With age, the mineralization decreased (r=-0.587, p=0.005) while the carbonate substitution increased (r=0.728, p<0.001). Age showed no significant associations with nanoindentation parameters. The present findings suggest that, at the tissue-level, the viscoelastic properties of trabecular bone are related to the changes in characteristics of bone mineral. This association may be independent of human age.
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