| 1. |
- Raina, Deepak Bushan, et al.
(författare)
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A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.
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| 2. |
- Cann, Sophie Le, et al.
(författare)
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Spatio-temporal evolution of hydroxyapatite crystal thickness at the bone-implant interface
- 2020
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 116, s. 391-399
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Tidskriftsartikel (refereegranskat)abstract
- A better understanding of bone nanostructure around the bone-implant interface is essential to improve longevity of clinical implants and decrease failure risks. This study investigates the spatio-temporal evolution of mineral crystal thickness and plate orientation in newly formed bone around the surface of a metallic implant. Standardized coin-shaped titanium implants designed with a bone chamber were inserted into rabbit tibiae for 7 and 13 weeks. Scanning measurements with micro-focused small-angle X-ray scattering (SAXS) were carried out on newly formed bone close to the implant and in control mature cortical bone. Mineral crystals were thinner close to the implant (1.8 ± 0.45 nm at 7 weeks and 2.4 ± 0.57 nm at 13 weeks) than in the control mature bone tissue (2.5 ± 0.21 nm at 7 weeks and 2.8 ± 0.35 nm at 13 weeks), with increasing thickness over healing time (+30 % in 6 weeks). These results are explained by younger bone close to the implant, which matures during osseointegration. Thinner mineral crystals parallel to the implant surface within the first 100 µm close to the implant indicate that the implant affects bone ultrastructure close to the implant, potentially due to heterogeneous interfacial stresses, and suggest a longer maturation process of bone tissue and difficulty in binding to the metal. The bone growth kinetics within the bone chamber was derived from the spatio-temporal evolution of bone tissue's nanostructure, coupled with microtomographic imaging. The findings indicate that understanding mineral crystal thickness or plate orientation can improve our knowledge of osseointegration.
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| 3. |
- Gustafsson, Anna, et al.
(författare)
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Linking multiscale deformation to microstructure in cortical bone using in situ loading, digital image correlation and synchrotron X-ray scattering
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 69, s. 323-331
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of fragility fractures is expected to increase in the near future due to an aging population. Therefore, improved tools for fracture prediction are required to treat and prevent these injuries efficiently. For such tools to succeed, a better understanding of the deformation mechanisms in bone over different length scales is needed. In this study, an experimental setup including mechanical tensile testing in combination with digital image correlation (DIC) and small/wide angle X-ray scattering (SAXS/WAXS) was used to study deformation at multiple length scales in bovine cortical bone. Furthermore, micro-CT imaging provided detailed information about tissue microstructure. The combination of these techniques enabled measurements of local deformations at the tissue- and nanoscales. The orientation of the microstructure relative to the tensile loading was found to influence the strain magnitude on all length scales. Strains in the collagen fibers were 2-3 times as high as the strains found in the mineral crystals for samples with microstructure oriented parallel to the loading. The local tissue strain at fracture was found to be around 0.5%, independent of tissue orientation. However, the maximum force and the irregularity of the crack path were higher when the load was applied parallel to the tissue orientation. This study clearly shows the potential of combining these different experimental techniques concurrently with mechanical testing to gain a better understanding of bone damage and fracture over multiple length scales in cortical bone. Statement of Significance: To understand the pathophysiology of bone, it is important to improve our knowledge about the deformation and fracture mechanisms in bone. In this study, we combine several recently available experimental techniques with mechanical loading to investigate the deformation mechanisms in compact bone tissue on several length scales simultaneously. The experimental setup included mechanical tensile testing in combination with digital image correlation, microCT imaging, and small/wide angle X-ray scattering.The combination of techniques enabled measurements of local deformations at the tissue- and nanoscales. The study clearly shows the potential of combining different experimental techniques concurrently with mechanical testing to gain a better understanding of structure-property-function relationships in bone tissue.
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| 4. |
- Khayyeri, Hanifeh, et al.
(författare)
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A novel semi-automatic hip morphology assessment tool is more accurate than manual radiographic evaluations
- 2020
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Ingår i: Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization. - : Informa UK Limited. - 2168-1163 .- 2168-1171. ; 8:1, s. 76-86
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Tidskriftsartikel (refereegranskat)abstract
- Radiological and pathological characteristics of hip osteoarthritis (OA) is joint-space loss due to degradation of articular cartilage. However, patients with early-stage OA do not yet show any radiological signs, which leaves them without diagnosis and treatment. This study evaluates the potential of a novel tool to identify pre-radiographic OA changes based on hip bone morphology. Two statistical appearance models for femur and pelvis were used to estimate the 3Dmorphology of the hip bones based on planar radiographs from patients. Well-known hip geometrical parameters (n = 22) were computed from patient CT scans (truth), 3D reconstructions (new method) and radiographs (calculated manually). The methods were compared by measuring relative error to truth. The new method was significantly more accurate in calculating hip geometrical parameters than the manual 2D calculations. The proposed approach could also capture rotational parameters like cross-over sign and anterior wall sign (100% correct predictions). The method can successfully reconstruct 3D hip shapes and densities for patients that have not yet developed severe osteoarthritis, and provided higher precision than manual estimations. Thus, it may be used to calculate morphological parameters that are predictors of OA and can become a powerful tool in human hip OA research and diagnostics.
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| 5. |
- Movérare-Skrtic, Sofia, et al.
(författare)
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Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.
- 2014
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 20:11, s. 1279-88
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Notermans, Thomas, et al.
(författare)
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Predicting the formation of different tissue types during Achilles tendon healing using mechanoregulated and oxygen-regulated frameworks
- 2023
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Ingår i: Biomechanics and Modeling in Mechanobiology. - : Springer Science and Business Media LLC. - 1617-7959 .- 1617-7940. ; 22:2, s. 655-667
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Tidskriftsartikel (refereegranskat)abstract
- During Achilles tendon healing in rodents, besides the expected tendon tissue, also cartilage-, bone- and fat-like tissue features have been observed during the first twenty weeks of healing. Several studies have hypothesized that mechanical loading may play a key role in the formation of different tissue types during healing. We recently developed a computational mechanobiological framework to predict tendon tissue production, organization and mechanical properties during tendon healing. In the current study, we aimed to explore possible mechanobiological related mechanisms underlying formation of other tissue types than tendon tissue during tendon healing. To achieve this, we further developed our recent framework to predict formation of different tissue types, based on mechanobiological models established in other fields, which have earlier not been applied to study tendon healing. We explored a wide range of biophysical stimuli, i.e., principal strain, hydrostatic stress, pore pressure, octahedral shear strain, fluid flow, angiogenesis and oxygen concentration, that may promote the formation of different tissue types. The numerical framework predicted spatiotemporal formation of tendon-, cartilage-, bone- and to a lesser degree fat-like tissue throughout the first twenty weeks of healing, similar to recent experimental reports. Specific features of experimental data were captured by different biophysical stimuli. Our modeling approach showed that mechanobiology may play a role in governing the formation of different tissue types that have been experimentally observed during tendon healing. This study provides a numerical tool that can contribute to a better understanding of tendon mechanobiology during healing. Developing these tools can ultimately lead to development of better rehabilitation regimens that stimulate tendon healing and prevent unwanted formation of cartilage-, fat- and bone-like tissues.
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| 7. |
- Orozco, Gustavo A., et al.
(författare)
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Crack propagation in articular cartilage under cyclic loading using cohesive finite element modeling
- 2022
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Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- Severe joint injuries often involve cartilage defects that propagate after mechanical loading. The propagation of these lesions may contribute to the development of post-traumatic osteoarthritis (PTOA). However, the mechanisms behind their propagation remain unknown. Currently, no numerical predictive methods exist for estimating crack propagation in cartilage under cyclic loading, yet they would provide essential insights into crack growth in injured tissue after trauma. Here, we present a numerical approach to estimate crack propagation in articular cartilage under cyclic loading using a cohesive damage model. Four different material models for cartilage (hyperelastic, poro-hyperelastic, poro-hyper-viscoelastic, and fibril-reinforced poro-hyperelastic (FRPHE) with different collagen orientations) were implemented. Our numerical cohesive damage model was able to replicate the experimental crack length reported in the literature, showing greater crack length with an increasing number of loading cycles. Damage initiation stress (4.35–4.73 MPa) and fracture energy (0.97–1.55 N/mm) values obtained for the poro-hyperelastic, poro-hyper-viscoelastic, and parallel-FRPHE models were within the range of what has been reported previously. The crack growth predictions obtained by the FRPHE models showed the influence of anisotropy of the fibrillar matrix on the cartilage response. Our results indicate that our cohesive damage model could potentially be used to estimate the adverse conditions in injured soft tissue such as osteochondral lesions, menisci tears, or partial ligament ruptures under (ab)normal biomechanical scenarios.
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| 8. |
- Grassi, Lorenzo, et al.
(författare)
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Validation of 3d finite element models from simulated Dxa images for Biofidelic simulations of sideways fall impact to the hip
- 2020
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Computed tomography (CT)-derived finite element (FE) models have been proposed as a tool to improve the current clinical assessment of osteoporosis and personalized hip fracture risk by providing an accurate estimate of femoral strength. However, this solution has two main drawbacks, namely: (i) 3D CT images are needed, whereas 2D dual-energy x-ray absorptiometry (DXA) images are more generally available, and (ii) quasi-static femoral strength is predicted as a surrogate for fracture risk, instead of predicting whether a fall would result in a fracture or not. The aim of this study was to combine a biofidelic fall simulation technique, based on 3D computed tomography (CT) data with an algorithm that reconstructs 3D femoral shape and BMD distribution from a 2D DXA image. This approach was evaluated on 11 pelvis-femur constructs for which CT scans, ex vivo sideways fall impact experiments and CT-derived biofidelic FE models were available. Simulated DXA images were used to reconstruct the 3D shape and bone mineral density (BMD) distribution of the left femurs by registering a projection of a statistical shape and appearance model with a genetic optimization algorithm. The 2D-to-3D reconstructed femurs were meshed, and the resulting FE models inserted into a biofidelic FE modeling pipeline for simulating a sideways fall. The median 2D-to-3D reconstruction error was 1.02 mm for the shape and 0.06 g/cm3 for BMD for the 11 specimens. FE models derived from simulated DXAs predicted the outcome of the falls in terms of fracture versus non-fracture with the same accuracy as the CT-derived FE models. This study represents a milestone towards improved assessment of hip fracture risk based on widely available clinical DXA images.
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| 9. |
- Kok, Joeri, et al.
(författare)
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Femoral strength and strains in sideways fall : Validation of finite element models against bilateral strain measurements
- 2021
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 122
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Tidskriftsartikel (refereegranskat)abstract
- Low impact falls to the side are the main cause of hip fractures in elderly. Finite element (FE) models of the proximal femur may help in the assessment of patients at high risk for a hip fracture. However, extensive validation is essential before these models can be used in a clinical setting. This study aims to use strain measurements from bilateral digital image correlation to validate an FE model against ex vivo experimental data of proximal femora under a sideways fall loading condition. For twelve subjects, full-field strain measurements were available on the medial and lateral side of the femoral neck. In this study, subject-specific FE models were generated based on a consolidated procedure previously validated for stance loading. The material description included strain rate dependency and separate yield and fracture strain limits in tension and compression. FE predicted fracture force and experimentally measured peak forces showed a strong correlation (R2 = 0.92). The FE simulations predicted the fracture initiation within 3 mm distance of the experimental fracture line for 8/12 subjects. The predicted and measured strains correlated well on both the medial side (R2 = 0.87) and the lateral side (R2 = 0.74). The lower correlation on the lateral side is attributed to the irregularity of the cortex and presence of vessel holes in this region. The combined validation against bilateral full-field strain measurements and peak forces has opened the door for a more elaborate qualitative and quantitative validation of FE models of femora under sideways fall loading.
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| 10. |
- Notermans, Thomas, et al.
(författare)
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Predicting the effect of reduced load level and cell infiltration on spatio-temporal Achilles tendon healing
- 2021
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290.
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Tidskriftsartikel (refereegranskat)abstract
- Mechanobiology plays an important role in tendon healing. However, the relationship between mechanical loading and spatial and temporal evolution of tendon properties during healing is not well understood. This study builds on a recently presented mechanoregulatory computational framework that couples mechanobiological tendon healing to tissue production and collagen orientation. In this study, we investigated how different magnitudes of mechanical stimulation (principal strain) affect the spatio-temporal evolution of tissue production and the temporal evolution of elastic and viscoelastic mechanical parameters. Specifically, we examined the effect of cell infiltration (mimicking migration and proliferation) in the callus on the resulting tissue production by modeling production to depend on local cell density. The model predictions were carefully compared with experimental data from Achilles tendons in rats, at 1, 2 and 4 weeks of healing. In the experiments, the rat tendons had been subjected to free cage activity or reduced load levels through intramuscular botox injections. The simulations that included cell infiltration and strain-regulated collagen production predicted spatio-temporal tissue distributions and mechanical properties similarly to that observed experimentally. In addition, lack of matrix-producing cells in the tendon core during early healing may result in reduced collagen content, regardless of the daily load level. This framework is the first to computationally investigate mechanobiological mechanisms underlying spatial and temporal variations during tendon healing for various magnitudes of loading. This framework will allow further characterization of biomechanical, biological, or mechanobiological processes underlying tendon healing.
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