Search PubMed⌕ Search

Biomedical subjects

H Weinans

Publications and source records attributed to H Weinans.

At least 37 records · Page 2Linked to original sources
PubMed2002

Cell and nucleus deformation in compressed chondrocyte-alginate constructs: temporal changes and calculation of cell modulus.

Mechanical loading is essential for the homeostasis of articular cartilage and may be necessary for achieving functional tissue engineered cartilage repair using isolated cells seeded in scaffolds such as alginate. Chondrocyte mechanotransduction is poorly understood, but may involve cell deformation and associated distortion of intracellular organelles. The present study used confocal microscopy to examine cell and nucleus morphology in isolated chondrocytes compressed in alginate constructs. Compression of 2% alginate resulted in cell deformation from a spherical to an oblate ellipsoid morphology with conservation of cell volume. Cell deformation was associated with deformation, to a lesser degree, of the nucleus. Despite constant cell deformation over a 25 min period of static compression, the nucleus deformation reduced significantly, particularly in the axis perpendicular to the applied compression. Constructs made of a lower alginate concentration exhibited a reduced compressive modulus with an altered cellular response to compression. In 1.2% alginate, compression resulted in cell deformation which was initially of a similar magnitude to that in 2% alginate but subsequently reduced over a 60 min period reflecting the viscoelastic behaviour of the gel. This phenomenon enabled the calculation of a stress-strain relationship for the cell with an estimated Young's modulus value of approx. 3 kPa.

Alginates↗
PubMed2002

ERK activation and alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts.

Osteoblast growth and differentiation are critical processes for bone development and maintenance, and are regulated by both humoral and mechanical factors. Humoral (hormonal) factors can affect gene transcription via MAPkinases, e.g., extracellular signal-regulated kinase (ERK). We studied whether the ERK pathway is also involved in processing mechanical inputs in human bone cells. Exposing MG63 cells to physiologically relevant levels of fluid flow resulted in ERK phosphorylation. Genistein blocked this response, indicating that it is dependent on tyrosine phosphorylation. Furthermore, alpha v beta 3 integrins were activated in response to fluid flow, as shown by recruitment of adaptor molecule Shc and clustering of alpha v beta 3 in focal adhesion-like structures. Antibodies blocking formation of beta 1 or beta 3 integrin-matrix interactions or RGD peptides could not inhibit fluid flow-induced ERK phosphorylation, suggesting that formation of new integrin-matrix interactions is not essential for this response and that other upstream mechanosensors regulate induction of ERK phosphorylation in response to fluid flow in human bone cells.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Cancellous bone mechanical properties from normals and patients with hip fractures differ on the structure level, not on the bone hard tissue level.

Osteoporosis is currently defined in terms of low bone mass. However, the source of fragility leading to fracture has not been adequately described. In particular, the contributions of bone tissue properties and architecture to the risk or incidence of fracture are poorly understood. In an earlier experimental study, it was found that the architectural anisotropy of cancellous bone from the femoral heads of fracture patients was significantly increased compared with age- and density-matched control material (Ciarelli et al., J Bone Miner Res 15:32-40; 2000). Using a combination of compression testing and micro-finite element analysis on a subset of cancellous bone specimens from that study, we calculated the hard tissue mechanical properties and the apparent (macroscopic) mechanical properties. The tissue modulus was 10.0 GPa (SD 2.2) for the control group and 10.8 GPa (SD 3.3) for the fracture group (not significant). There were no differences in either the apparent yield strains, percentages of highly strained tissue, or the relationship between apparent yield stress and apparent elastic modulus. Hence, a difference in the tissue yield properties is unlikely. At the apparent level, the fracture group had a significantly decreased transverse stiffness, resulting in increased mechanical anisotropy. These changes suggest that bone in the fracture group was "overadapted" to the primary load axis, at the cost of fragility in the transverse direction. We conclude that individuals with a history of osteoporotic fractures do not have weaker bone tissue. Architectural and mechanical anisotropy alone renders their bone weaker in the nonprimary loading direction.

Aged↗
PubMed2001

Osteoporosis changes the amount of vertebral trabecular bone at risk of fracture but not the vertebral load distribution.

STUDY DESIGN: A finite-element study to investigate the amount of trabecular bone at risk of fracture and the distribution of load between trabecular core and cortical shell, for healthy, osteopenic, and osteoporotic vertebrae. OBJECTIVES: To determine differences between healthy, osteopenic, and osteoporotic vertebrae with regard to the risk of fracture and the load distribution. SUMMARY OF BACKGROUND DATA: The literature contains no reports on the effects of osteopenia and osteoporosis on load distribution in vertebral bodies, nor any reports on the amount of trabecular bone at risk of fracture. METHODS: Computed tomography data of vertebral bodies were used to construct patient-specific finite-element models. These models were then used in finite-element analyses to determine the physiologic stresses and strains in the vertebrae. RESULTS: For all three classes of vertebrae the contribution of the trabecular core to the total load transfer decreased from about 70% near the endplates to about 50% in the midtransverse region. The amount of trabecular bone that is at risk of fracture was about 1% for healthy vertebrae, about 3% for osteopenic vertebrae, and about 16% for osteoporotic vertebrae. CONCLUSIONS: Our finite-element models indicated that neither osteopenia nor osteoporosis had any effect on the contribution of the trabecular core to the total load placed on the vertebra. The trabecular core carried about half the load. Our finite-element models indicated that osteoporosis had a significant effect on the amount of trabecular bone at risk of fracture, which increased from about 1% in healthy vertebrae to about 16% for osteoporotic vertebrae.

Adult↗
PubMed2001

Introduction and evaluation of a gray-value voxel conversion technique.

In micro finite element analyses (microFEA) of cancellous bone, the 3D-imaging data that the FEA-models are based on, contain a range of gray-values. In the construction of the eventual FEA-model, these gray-values are commonly thresholded. Although thresholding is successful at small voxel sizes, at larger voxel sizes there is substantial loss of trabecular connectivity. We propose a new method: the gray-value method, where the microFEA-models use the information within the 3D-imaging data directly, without prior thresholding. Our question was twofold. First, how does the gray-value method compare to both plain and mass-compensated thresholding? Second, what is the effect of element size on the results obtained with the gray-value method? We used nine microCT-scans of human vertebral cancellous bone. These were degraded to represent different resolutions, and converted into microFEA-models using plain thresholding, mass-compensated thresholding, and the gray-value method. The apparent elastic moduli of the specimens were determined using microFEA. The different methods were compared on the basis of the apparent elastic moduli, compared to those calculated for a 28 microm reference model. The results showed that the gray-value method greatly improves the results relative to other methods. The gray-value method gives accurate predictions of the apparent elastic moduli, for voxel sizes up to one trabecular thickness (Tb.Th.). For voxel sizes greater than one Tb.Th. the accuracy, although still better than for both thresholding methods, becomes increasingly worse.

Biomechanical Phenomena↗
PubMed2001

Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution.

The bone remodeling process takes place at the surface of trabeculae and results in a non-uniform mineral distribution. This will affect the mechanical properties of cancellous bone, because the properties of bone tissue depend on its mineral content. We investigated how large this effect is by simulating several non-uniform mineral distributions in 3D finite element models of human trabecular bone and calculating the apparent stiffness of these models. In the 'linear model' we assumed a linear relation between mineral content and Young's modulus of the tissue. In the 'exponential model' we included an empirical exponential relation in the model. When the linear model was used the mineral distribution slightly changed the apparent stiffness, the difference varied between an 8% decrease and a 4% increase compared to the uniform model with the same BMD. The exponential model resulted in up to 20% increased apparent stiffness in the main load-bearing direction. A thin less mineralized surface layer (28 microm) and highly mineralized interstitial bone (mimicking mineralization resulting from anti-resorptive treatment) resulted in the highest stiffness. This could explain large reductions in fracture risk resulting from small increases in BMD. The non-uniform mineral distribution could also explain why bone tissue stiffness determined using nano-indentation is usually higher than finite element (FE)-determined stiffness. We conclude that the non-uniform mineral distribution in trabeculae does affect the mechanical properties of cancellous bone and that the tissue stiffness determined using FE-modeling could be improved by including detailed information about mineral distribution in trabeculae in the models.

Adult↗
PubMed2001

A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage.

In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis.

Aged↗
PubMed2001

Mechanical consequences of bone loss in cancellous bone.

The skeleton is continuously being renewed in the bone remodeling process. This prevents accumulation of damage and adapts the architecture to external loads. A side effect is a gradual decrease of bone mass, strength, and stiffness with age. We investigated the effects of bone loss on the load distribution and mechanical properties of cancellous bone using three-dimensional (3D) computer models. Several bone loss scenarios were simulated. Bone matrix was removed at locations of high strain, of low strain, and random throughout the architecture. Furthermore, resorption cavities and thinning of trabeculae were simulated. Removal of 7% of the bone mass at highly strained locations had deleterious effects on the mechanical properties, while up to 50% of the bone volume could be removed at locations of low strain. Thus, if remodeling would be initiated only at highly strained locations, where repair is likely needed, cancellous bone would be continuously at risk of fracture. Thinning of trabeculae resulted in relatively small decreases in stiffness; the same bone loss caused by resorption cavities caused large decreases in stiffness and high strain peaks at the bottom of the cavities. This explains that a reduction in the number and size of resorption cavities in antiresorptive drug treatment can result in large reductions in fracture risk, with small increases in bone mass. Strains in trabeculae surrounding a cavity increased by up to 1,000 microstrains, which could lead to bone apposition. These results give insight in the mechanical effects of bone remodeling and resorption at trabecular level.

Bone Remodeling↗
PubMed2001

A three-dimensional simulation of age-related remodeling in trabecular bone.

After peak bone mass has been reached, the bone remodeling process results in a decrease in bone mass and strength. The formation deficit, the deficit of bone formation compared with previous resorption, results in bone loss. Moreover, trabeculae disconnected by resorption cavities probably are not repaired. The contributions of these mechanisms to the total bone loss are unclear. To investigate these contributions and the concomitant changes in trabecular architecture and mechanical properties, we made a computer simulation model of bone remodeling using microcomputed tomography (micro-CT) scans of human vertebral trabecular bone specimens. Up to 50 years of physiological remodeling were simulated. Resorption cavities were created and refilled 3 months later. These cavities were not refilled completely, to simulate the formation deficit. Disconnected trabeculae were not repaired; loose fragments generated during the simulation were removed. Resorption depth, formation deficit, and remodeling space were based on biological data. The rate of bone loss varied between 0.3% and 1.1% per year. Stiffness anisotropy increased, and morphological anisotropy (mean intercept length [MIL]) was almost unaffected. Connectivity density increased or decreased, depending on the remodeling parameters. The formation deficit accounted for 69-95%, disconnected trabeculae for 1-21%, and loose fragments for 1-17% of the bone loss. Increasing formation deficit from 1.8% to 5.4% tripled bone loss but only doubled the decrease in stiffness. Increasing resorption depth from 28 to 56 microm slightly increased bone loss but drastically decreased stiffness. Decreasing the formation deficit helps to prevent bone loss, but reducing resorption depth is more effective in preventing loss of mechanical stiffness.

Adult↗
PubMed2000

Monitoring water content in deforming intervertebral disc tissue by finite element analysis of MRI data.

Mechanical loading, occurring during normal daily life, causes fluid to be expelled from intervertebral discs. Excessive fluid loss during heavy loading might make the disc more vulnerable to damage. In this study, fluid loss was investigated in vitro through monitoring the loss of MRI signal intensity in four bovine coccygeal intervertebral discs, compressed at 2000 N during 1.5 hr. The MRI signals were analyzed with the aid of finite element models to account for the deformation of the tissue. A gradual signal loss over time was found during loading, the most pronounced loss occurring in the central disc region. Initial patterns of signal distribution were quite variable between specimens but repeatable within specimens.

Animals↗
PubMed2000

Sensitivity of periprosthetic stress-shielding to load and the bone density-modulus relationship in subject-specific finite element models.

Subject-specific finite element (FE) computer models of the proximal femur in hip replacement could potentially predict stress-shielding and subsequent bone loss in individual patients. Before such predictions can be made, it is important first to determine if between subject differences in stress-shielding are sensitive to poorly defined parameters such as the load and the bone material properties. In this study we investigate if subject-specific FE models provide consistent stress-shielding patterns in the bone, independent of the choice of the loading conditions and the bone density-modulus relationship used in the computer model. FE models of two right canine femurs with and without implants were constructed based on contiguous computed tomography (CT) scans so that subject-specific estimates of stress-shielding could be calculated. Four different loading conditions and two bone density-modulus relationships were tested. Stress-shielding was defined as the decrease of strain energy per gram bone mass in the femur with the implant in place relative to the intact femur. The analyses showed that for the four loading conditions and two bone density-modulus relationships the difference in stress-shielding between the two subjects was essentially constant (1% variation) when the same loading condition and density-modulus relationship was used for both subjects. The severity of stress-shielding within a subject was sensitive to these input parameters, varying up to 20% in specific regions with a change in loading conditions and up to 10% for a change in the assumed density-modulus relationship. We conclude that although the choice of input parameters can substantially affect stress-shielding in an individual, this choice had virtually no effect on the relative differences in femoral periprosthetic stress-shielding between individuals. Thus, while care should be taken in the interpretation of the absolute value of stress-shielding calculated with these type of models, subject-specific FE models may be useful for explaining the variation in bone adaptation responsiveness between different subjects in experimental or clinical studies.

Animals↗
PubMed2000

Parallel plate model for trabecular bone exhibits volume fraction-dependent bias.

Unbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal tibia, canine distal femur, rat tail, and pig spine and scanned in a micro-CT scanner. Trabecular thickness, trabecular spacing, and trabecular number were calculated using the parallel plate model. Direct thickness, and spacing and connectivity density were calculated using unbiased three-dimensional methods. Both thickness and spacing calculated using the plate model were well correlated to the direct three-dimensional measures (r(2) = 0. 77-0.92). The correlation between trabecular number and connectivity density varied greatly (r(2) = 0.41-0.94). Whereas trabecular thickness was consistently underestimated using the plate model, trabecular spacing was underestimated at low volume fractions and overestimated at high volume fractions. Use of the plate model resulted in a volume-dependent bias in measures of thickness and spacing (p < 0.001). This was a result of the fact that samples of low volume fraction were much more "rod-like" than those of the higher volume fraction. Our findings indicate that the plate model provides biased results, especially when populations with different volume fractions are compared. Therefore, we recommend direct thickness measures when three-dimensional data sets are available.

Adolescent↗
PubMed1999

Cryosurgery in long bones; an experimental study of necrosis and revitalization in rabbits.

Cryosurgery is an established adjuvant treatment of bone tumors which reduces the local recurrence rate. In this study, cryosurgical experiments were carried out in rabbits to study the temperature field, the extent of necrosis, and the revitalization process in order to optimize treatment. Intramedullary freezing of long bones with a closed liquid nitrogen cryoprobe and three consecutive sessions induces osteonecrosis down to the -10 degrees C isotherm without compromising the soft tissues. The application of a tourniquet does not influence the thermodynamics. The revitalization process is distinguished into an osteogenic and a remodelling phase. In rabbits, there is an obvious periosteal osteogenesis starting from 1 week after operation and overlapping the remodelling phase, which starts between 3 and 5 weeks after operation. Two out of eight rabbits sustained a pathologic fracture within 3 weeks of cryosurgery. No pathologic fractures were encountered during the remodelling phase, probably because of the profuse periosteal bone apposition that added mechanical strength. In clinical practice, no profound periosteal bone apposition and a high risk for pathologic fractures during the remodelling phase were noted. Future research should focus on bone strength during the remodelling phase of cryosurgically treated long bones, to decide on the role of preventive osteosynthesis or postoperative restrictions. This animal model is not advised for these biomechanical experiments because of its profuse periosteal bone apposition.

Animals↗
PubMed1999

Correlation between pre-operative periprosthetic bone density and post-operative bone loss in THA can be explained by strain-adaptive remodelling.

Periprosthetic adaptive bone remodelling after total hip arthroplasty can be simulated in computer models, combining bone remodelling theory with finite element analysis. Patient specific three-dimensional finite element models of retrieved bone specimens from an earlier bone densitometry (DEXA) study were constructed and bone remodelling simulations performed. Results of the simulations were analysed both qualitatively and quantitatively. Patterns of predicted bone loss corresponded very well with the DEXA measurements on the retrievals. The amount of predicted bone loss, measured quantitatively by simulating DEXA on finite element models, was found to be inversely correlated with the initial bone mineral content. It was concluded that the same clinically observed correlation can therefore be explained by mechanically induced remodelling. This finding extends the applicability of numerical pre-clinical testing to the analysis of interaction between implant design and initial state of the bone.

Absorptiometry, Photon↗
PubMed1999

Fractures of the lumbar vertebral endplate in the etiology of low back pain: a hypothesis on the causative role of spinal compression in aspecific low back pain.

It is hypothesized that, in a large number of cases of aspecific low back pain, the primary cause of the pain is a fracture of the vertebral endplate caused by compression forces. Clinical studies have shown that, in many low back pain patients, damage of the vertebral bodies and or the intervertebral disc is present. In vitro studies reveal that the most likely type of failure of this anterior part of the spine is a fracture of the endplate as a result of compression. The high incidence of aspecific low back pain concurs with the likeliness of compression fractures of the endplate to occur in everyday life. Furthermore, epidemiological findings and the natural history of low back pain appear to be in line with the proposed hypothesis.

Disease Progression↗
PubMed1998

Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques.

In this study, we investigate if finite element (FE) analyses of human trabecular bone architecture based on 168 microm images can provide relevant information about the bone mechanical characteristics. Three human trabecular bone samples, one taken from the femoral head, one from the iliac crest, and one from the lumbar spine, were imaged with micro-computed tomography (micro-CT) using a 28 microm resolution. After reconstruction the resolution was coarsened to 168 microm. First, all reconstructions were thresholded and directly converted to FE-models built of hexahedral elements. For the coarser resolutions of two samples, this resulted in a loss of trabecular connections and a subsequent loss of stiffness. To reduce this effect, a tetrahedral element meshing based on the marching cubes algorithm, as well as a modified hexahedron meshing, which thresholds the image such that load carrying bone mass is preserved, were employed. For each sample elastic moduli and tissue Von Mises stresses of the three different 168 microm models were compared to those from the hexahedron 28 microm model. For one sample the hexahedron meshing at 168 microm produced excellent results. For the other two samples the results obtained from the hexahedral models at 168 microm resolution were poor. Considerably better results were attained for these samples when using the mass-compensated or tetrahedron meshing techniques. We conclude that the accuracy of the FE-models at 168 microm strongly depends on the bone morphology, in particular its trabecular thickness. A substantial loss of trabecular connections during the hexahedron meshing process indicates that poor FE results will be obtained. In this case the tetrahedron or mass-compensated hexahedron meshing techniques can reduce the loss of connections and produce better results than the plain hexahedron meshing techniques.

Algorithms↗
PubMed1998

Finite element aided tracking of signal intensity changes in deforming intervertebral disc tissue.

Tracking of signal intensity changes in soft tissue over time is often hampered by deformation of the tissue. In this study a method is described that uses finite element modeling to compensate for tissue deformation. The method is applied to the quantification of fluid redistribution in an intervertebral disc that deforms under mechanical load. The clinical importance of this application emerges from the increased susceptibility of the intervertebral disc to damage after a period of mechanical loading. The study shows that the use of the finite element aided approach results in a detailed map of tissue MRI signal changes, where the distorting effects of tissue deformation are eliminated.

Animals↗