Adaptive changes in micromechanical environments of cancellous and cortical bone in response to in vivo loading and disuse

The skeleton accommodates changes in mechanical environments by increasing bone mass under increased loads and decreasing bone mass under disuse. However, little is known about the adaptive changes in micromechanical behavior of cancellous and cortical tissues resulting from loading or disuse. To address this issue, in vivo tibial loading and hindlimb unloading experiments were conducted on 16-week-old female C57BL/6J mice. Changes in bone mass and tissue-level strains in the metaphyseal cancellous and midshaft cortical bone of the tibiae, resulting from loading or unloading, were determined using microCT and finite element (FE) analysis, respectively. We found that loading- and unloading-induced changes in bone mass were more pronounced in the cancellous than cortical bone. Simulated FE-loading showed that a greater proportion of elements experienced relatively lower longitudinal strains following load-induced bone adaptation, while the opposite was true in the disuse model. While the magnitudes of maximum or minimum principal strains in the metaphyseal cancellous and midshaft cortical bone were not affected by loading, strains oriented with the long axis were reduced in the load-adapted tibia suggesting that loading-induced micromechanical benefits were aligned primarily in the loading direction. Regression analyses demonstrated that bone mass was a good predictor of bone tissue strains for the cortical bone but not for the cancellous bone, which has complex microarchitecture and spatially-variant strain environments. In summary, loading-induced micromechanical benefits for cancellous and cortical tissues are received primarily in the direction of force application and cancellous bone mass may not be related to the micromechanics of cancellous bone.     

Thermal analysis of bone cement polymerisation at the cement-bone interface

The two major problems that have been reported with the use of polymethylmethacrylate (PMMA) cement are thermal necrosis of surrounding bone due to the high heat generation during polymerisation and chemical necrosis due to unreacted monomer release. Computer models have been used to study the temperature and monomer distribution after cementation. In most of these models, however, polymerisation is modelled as temperature independent and cancellous bone is modelled as a continuum. Such models thus cannot account for the expected important role of the trabecular bone micro-structure. The aim of this study is to investigate the distribution of temperature and monomer leftover at the cancellous bone–cement interface during polymerisation for a realistic trabecular bone—cement micro-structure and realistic temperature-dependent polymerisation kinetics behaviour.

A 3-D computer model of a piece of bovine cancellous bone that underwent pressurization with bone–cement was generated using a micro-computed tomography scanner. This geometry was used as the basis for a finite element model and a temperature-dependent problem for bone cement polymerisation kinetics was solved to simulate the bone cement polymerisation process in the vicinity of the interface. The transient temperature field throughout the interface was calculated, along with the polymerisation fraction distribution in the cement domain.

The calculations revealed that the tips of the bone trabeculae that are embedded in the cement attain temperatures much higher than the average temperature of the bone volume. A small fraction of the bone (10%) is exposed to temperatures exceeding 70°C, but the exposure time to these high temperatures is limited to 50 s. In the region near the bone, the cement polymerisation fraction (about 84%) is less than that in the centre (where it is reaching values of over 96%). An important finding of this study thus is the fact that the bone tissue that is subjected to the highest temperatures is also subjected to high leftover monomer concentration. Furthermore the maximum bone temperature is reached relatively early, when monomer content in the neighbouring cement is still quite high.     

How plate positioning impacts the biomechanics of the open wedge tibial osteotomy; A finite element analysis

A numerical model of the medial open wedge tibial osteotomy based on the finite element method was developed. Two plate positions were tested numerically. In a configuration, (a), the plate was fixed in a medial position and (b) in an anteromedial position. The simulation took into account soft tissues preload, muscular tonus and maximal gait load.

The maximal stresses observed in the four structural elements (bone, plate, wedge, screws) of an osteotomy with plate in medial position were substantially higher (1.13–2.8 times more) than those observed in osteotomy with an anteromedial plate configuration. An important increase (1.71 times more) of the relative micromotions between the wedge and the bone was also observed. In order to avoid formation of fibrous tissue at the bone wedge interface, the osteotomy should be loaded under 18.8% (～50 kg) of the normal gait load until the osteotomy interfaces union is achieved.     

The effects of misalignment during in vivo loading of bone: Techniques to detect the proximity of objects in three-dimensional models

Theories of mechanical adaptation of bone suggest that mechanical loading causes bone formation at discrete locations within bone microstructure experiencing the greatest mechanical stress/strain. Experimental testing of such theories requires in vivo loading experiments and high-resolution finite element models to determine the distribution of mechanical stresses. Finite element models of in vivo loading experiments typically assume idealized boundary conditions with applied load perfectly oriented on the bone, however small misalignments in load orientation during an in vivo experiment are unavoidable, and potentially confound the ability of finite element models to predict locations of bone formation at the scale of micrometers. Here we demonstrate two different three-dimensional spatial correlation methods to determine the effects of misalignment in load orientation on the locations of high mechanical stress/strain in the rodent tail loading model. We find that, in cancellous bone, the locations of tissue with high stress are maintained under reasonable misalignments in load orientation (p<0.01). In cortical bone, however, angular misalignments in the dorsal direction can alter the locations of high mechanical stress, but the locations of tissue with high stress are maintained under other misalignments (p<0.01). We conclude that, when using finite element models of the rodent tail loading model, small misalignments in loading orientation do not affect the predicted locations of high mechanical stress within cancellous bone.     

A collagen-based interface construct for the assessment of cell-dependent mechanical integration of tissue surfaces

The interface between any newly engineered tissue and pre-existing tissue is of great importance to tissue engineering; however, this process has so far been largely ignored, with few reports regarding the mechanical strength of newly integrated connective tissues surfaces. A new model system has been developed to generate a well-defined interface between two collagen lattices: one pre-contracted by resident fibroblasts and the other a cell-free wrapping gel. This construct can be cultured for prolonged periods (>2 weeks) and can also be fitted onto a mechanical testing system to measure the interface adhesive strength at the end of the culture time. Interface adhesive strength shows a six-fold increase after 1 week in culture, compared with the time-zero baseline. Observations of cell migration across the interface suggest that cell translocation in the three-dimensional matrix might play an important role in the integration process. In this new controlled geometry, normal and shear stresses at the interface can be analysed by finite element modelling and the areas at which debonding starts can be defined. The current experimental design permits solid multiple (homogeneous or heterogeneous) interface formation in vitro with a well-defined geometry and the possibility of measuring mechanical linkage. This design should enable many other factors affecting cell-driven interface strengthening to be investigated. This study was supported by the Fifth Framework Programme of the European Commission, “Biomechanical Interactions in Tissue Engineering and Surgical Repair (BITES)”.     

Relation between subject-specific hip joint loading, stress distribution in the proximal femur and bone mineral density changes after total hip replacement

In the prediction of bone remodelling processes after total hip replacement (THR), modelling of the subject-specific geometry is now state-of-the-art. In this study, we demonstrate that inclusion of subject-specific loading conditions drastically influences the calculated stress distribution, and hence influences the correlation between calculated stress distributions and changes in bone mineral density (BMD) after THR.For two patients who received cementless THR, personalized finite element (FE) models of the proximal femur were generated representing the pre- and post-operative geometry. FE analyses were performed by imposing subject-specific three-dimensional hip joint contact forces as well as muscle forces calculated based on gait analysis data. Average values of the von Mises stress were calculated for relevant zones of the proximal femur. Subsequently, the load cases were interchanged and the effect on the stress distribution was evaluated. Finally, the subject-specific stress distribution was correlated to the changes in BMD at 3 and 6 months after THR.We found subject-specific differences in the stress distribution induced by specific loading conditions, as interchanging of the loading also interchanged the patterns of the stress distribution. The correlation between the calculated stress distribution and the changes in BMD were affected by the two-dimensional nature of the BMD measurement.Our results confirm the hypothesis that inclusion of subject-specific hip contact forces and muscle forces drastically influences the stress distribution in the proximal femur. In addition to patient-specific geometry, inclusion of patient-specific loading is, therefore, essential to obtain accurate input for the analysis of stress distribution after THR.     

A model-based approach for estimation of changes in lumbar segmental kinematics associated with alterations in trunk muscle forces

The kinematics information from imaging, if combined with optimization-based biomechanical models, may provide a unique platform for personalized assessment of trunk muscle forces (TMFs). Such a method, however, is feasible only if differences in lumbar spine kinematics due to differences in TMFs can be captured by the current imaging techniques. A finite element model of the spine within an optimization procedure was used to estimate segmental kinematics of lumbar spine associated with five different sets of TMFs. Each set of TMFs was associated with a hypothetical trunk neuromuscular strategy that optimized one aspect of lower back biomechanics. For each set of TMFs, the segmental kinematics of lumbar spine was estimated for a single static trunk flexed posture involving, respectively, 40° and 10° of thoracic and pelvic rotations. Minimum changes in the angular and translational deformations of a motion segment with alterations in TMFs ranged from 0° to 0.7° and 0 mm to 0.04 mm, respectively. Maximum changes in the angular and translational deformations of a motion segment with alterations in TMFs ranged from 2.4° to 7.6° and 0.11 mm to 0.39 mm, respectively. The differences in kinematics of lumbar segments between each combination of two sets of TMFs in 97% of cases for angular deformation and 55% of cases for translational deformation were within the reported accuracy of current imaging techniques. Therefore, it might be possible to use image-based kinematics of lumbar segments along with computational modeling for personalized assessment of TMFs.     

A novel approach to modelling and simulating the contact behaviour between a human hand model and a deformable object

A deeper understanding of biomechanical behaviour of human hands becomes fundamental for any human hand-operated activities. The integration of biomechanical knowledge of human hands into product design process starts to play an increasingly important role in developing an ergonomic product-to-user interface for products and systems requiring high level of comfortable and responsive interactions. Generation of such precise and dynamic models can provide scientific evaluation tools to support product and system development through simulation. This type of support is urgently required in many applications such as hand skill training for surgical operations, ergonomic study of a product or system developed and so forth. The aim of this work is to study the contact behaviour between the operators' hand and a hand-held tool or other similar contacts, by developing a novel and precise nonlinear 3D finite element model of the hand and by investigating the contact behaviour through simulation. The contact behaviour is externalised by solving the problem using the bi-potential method. The human body's biomechanical characteristics, such as hand deformity and structural behaviour, have been fully modelled by implementing anisotropic hyperelastic laws. A case study is given to illustrate the effectiveness of the approach.     

Biomechanical investigation of post-operative C5 palsy due to ossification of the posterior longitudinal ligament in different types of cervical spinal alignment

Post-operative C5 palsies are among the most common complications seen after cervical surgery for ossification of the posterior longitudinal ligament (OPLL). Although C5 palsy is a well-known complication of cervical spine surgery, its pathogenesis is poorly understood and depends on many other factors. In this study, a finite element model of the cervical spine and spinal cord-nerve roots complex structures was developed. The changes in stress in the cord and nerve roots, posterior shift of the spinal cord, and displacement and elongation of the nerve roots after laminectomy for cervical OPLL were analyzed for three different cervical sagittal alignments (lordosis, straight, and kyphosis). The results suggest that high stress concentrated on the nerve roots after laminectomy could be the main cause of C5 palsy because ossification of ligaments increases spinal cord shifting and root displacement. The type of sagittal alignment had no influence on changes in cord stress after laminectomy, although cases of kyphosis with a high degree of occupying ratio resulted in greater increases in nerve root stress after laminectomy. Therefore, kyphosis with a high OPLL occupying ratio could be a risk factor for poor surgical outcomes or post-operative complications and should be carefully considered for surgical treatment.     

Generalized estimating equations: A pragmatic and flexible approach to the marginal GLM modelling of correlated data in the behavioural sciences

Within behavioural research, non‐normally distributed data with a complicated structure are common. For instance, data can represent repeated observations of quantities on the same individual. The regression analysis of such data is complicated both by the interdependency of the observations (response variables) and by their non‐normal distribution. Over the last decade, such data have been more and more frequently analysed using generalized mixed‐effect models. Some researchers invoke the heavy machinery of mixed‐effect modelling to obtain the desired population‐level (marginal) inference, which can be achieved by using simpler tools—namely by marginal models. This paper highlights marginal modelling (using generalized estimating equations [GEE]) as an alternative method. In various situations, GEE can be based on fewer assumptions and directly generate estimates (population‐level parameters) which are of immediate interest to the behavioural researcher (such as population means). Using four examples from behavioural research, we demonstrate the use, advantages, and limits of the GEE approach as implemented within the functions of the ‘geepack’ package in R.     

A metabolomics approach to investigate the proceedings of mitochondrial dysfunction in rats from prediabetes to diabetes

BackgroundDiabetes mellitus (DM) is a leading cause of preventable cardiovascular disease, but the metabolic changes from prediabetes to diabetes have not been fully clarified. This study implemented a metabolomics profiling platform to investigate the variations of metabolites and to elucidate their global profiling from metabolic syndrome to DM. Methods: Male Sprague-Dawley rats (n = 44) were divided into four groups. Three groups were separately fed with a normal diet, a high-fructose diet (HF), or a high-fat (HL) diet while one group was treated with streptozotocin. The HF and HL diet were meant to induce insulin resistance, obesity, and dyslipidemia, which known to induce DM. Results: The most significant metabolic variations in the DM group’s urine samples were the reduced release of citric acid cycle intermediates, the increase in acylcarnitines, and the decrease in urea excretion, all of which indicated energy metabolism abnormalities and mitochondrial dysfunction. Overall, the metabolic analysis revealed tryptophan metabolic pathway variations in the prediabetic phase, even though the mitochondrial function remains unaffected. Conclusion: This study show that widespread methylations and impaired tryptophan metabolism occur in metabolic syndrome and are then followed by a decline in citric acid cycle intermediates, indicating mitochondrial dysfunction in diabetes.