A novel approach to estimate trabecular bone anisotropy using a database approach

Continuum finite element (FE) models of bones have become a standard pre-clinical tool to estimate bone strength. These models are usually based on clinical CT scans and material properties assigned are chosen as isotropic based only on the density distribution. It has been shown, however, that trabecular bone elastic behavior is best described as orthotropic. Unfortunately, the use of orthotropic models in FE analysis derived from CT scans is hampered by the fact that the measurement of a trabecular orientation (fabric) is not possible from clinical CT images due to the low resolution of such images. In this study, we explore the concept of using a database (DB) of high-resolution bone models to derive the fabric information that is missing in clinical images. The goal of this study was to investigate if models with fabric derived from a relatively small database can already produce more accurate results than isotropic models.     

Subject-specific modeling of the scapula bone tissue adaptation

Adaptation of the scapula bone tissue to mechanical loading is simulated in the current study using a subject-specific three-dimensional finite element model of an intact cadaveric scapula. The loads experienced by the scapula during different types of movements are determined using a subject-specific large-scale musculoskeletal model of the shoulder joint. The obtained density distributions are compared with the CT-measured density distribution of the same scapula. Furthermore, it is assumed that the CT-measured density distribution can be estimated as a weighted linear combination of the density distributions calculated for different loads experienced during daily life. An optimization algorithm is used to determine the weighting factors of fourteen different loads such that the difference between the weighted linear combination of the calculated density distributions and the CT-measured density is minimal. It is shown that the weighted linear combination of the calculated densities matches the CT-measured density distribution better than every one of the density distributions calculated for individual movements. The weighting factors of nine out of fourteen loads were estimated to be zero or very close to zero. The five loads that had larger weighting factors were associated with either one of the following categories: (1) small-load small-angle abduction or flexion movements that occur frequently during our daily lives or (2) large-load large-angle abduction or flexion movements that occur infrequently during our daily lives.     

Femoral neck bone adaptation to weight-bearing physical activity by computational analysis

Individual differences in bone mass distribution at the proximal femur may be determined by daily weight-bearing physical activity (PA) since bone self-adapts according to the mechanical loads that is submitted. The aim of this study was to analyse computationally the effect of different weight-bearing PA types in the adaptation of the femoral neck (FN) by analysing regional differences in bone mineral density (BMD) at the integral FN and its superior, inferior, anterior and posterior subregions. To achieve this, it was adopted a 3-D femoral finite element (FE) model coupled with a suitable bone remodeling model. Different PA types were determined based both on ordinary lifestyle and mechanically more demanding PA as low magnitude impacts (L–I), moderate-magnitude impacts from odd directions (O–I) and high-magnitude vertical impacts (H–I). It was observed that as time spent in weight-bearing PA increases, BMD augment around the integral FN, but with different bone mass gain rates between subregions depending on the magnitude and directions of the hip contact forces; H–I was the type of weight-bearing PA which structurally most favor the gain of bone mass superiorly at the FN while both the H–I and the O–I types of PA promoted the largest bone mass gain rates at the anterior and posterior subregions of the FN. Because these types of weight-bearing PA were associated with a more uniform bone mass spatial distribution at the FN, they should provide a potential basis for targeted PA-based intervention programs for improving hip strength.     

Modelling external bone adaptation using evolutionary structural optimisation

External remodelling is significant in the bone healing process, and it is essential to predict the bone external shape in the design of artificial bone grafts. This paper demonstrates the effectiveness of the evolutionary structural optimisation (ESO) method for the simulation of bone morphology. A two-dimensional ESO strategy is developed which is capable of finding the modified bone topology beginning with any geometry under any loading conditions. The morphology of bone structure is described by the quantitative bone adaptation theory, which is integrated with the finite element method. The evolutionary topology optimisation process is introduced to find the bone shape. A rectangle, which occupies a larger space than the external shape of the bone structure, is specified as a design domain; the evolutionary process iteratively eliminates and redistributes material throughout the domain to obtain an optimum arrangement of bone materials. The technique has been tested on a wide range of examples. In this paper, the formation of trabecular bone architecture around an implant is studied; as another example, the growth of the coronal section of a vertebral body is predicted. The examples support the assertion that the external shape of bone structure can be successfully predicted by the proposed ESO procedure.     

A study of the viscoelastic effect in a bone remodeling model

The present paper addresses the following question can a simple regulatory bone remodeling model predict effects of viscosity on the trabecular morphology? For that, we propose an extension of a previous bone remodeling model by taking into account the viscosity properties of the tissue. Zener’s law is used to describe the mechanical behavior of the bone and a specific law of the apparent bone density rate is proposed. Based on stability analysis, numerical simulations are then performed to investigate the viscosity role on simulations of the bone remodeling process. We show that the viscous contribution affects the evolution of the apparent bone density, by slowing down the adaptation process, which seems to be confirmed by simulations with real data obtained from rat tibia.     

A generic 3-dimensional system to mimic trabecular bone surface adaptation

The paper presents the structure optimizing system based on surface remodelling. The grounds for algorithm formulation are given by the bone remodelling phenomenon leading to optimization of trabecular network in the bone. The assumptions, algorithms and limitations of the own mesh generator Cosmoprojector are described. Unlike other approaches, the system is able to mimic real bone evolution including tissue consolidation and separation. The article presents a closed system consisting of finite element mesh generation, decision criteria for structure adaptation and finite element analysis in parallel environment. It also provides some computation results obtained by using specially designed software.     

Density-based load estimation using two-dimensional finite element models: a parametric study

A parametric investigation was conducted to determine the effects on the load estimation method of varying: (1) the thickness of back-plates used in the two-dimensional finite element models of long bones, (2) the number of columns of nodes in the outer medial and lateral sections of the diaphysis to which the back-plate multipoint constraints are applied and (3) the region of bone used in the optimization procedure of the density-based load estimation technique. The study is performed using two-dimensional finite element models of the proximal femora of a chimpanzee, gorilla, lion and grizzly bear. It is shown that the density-based load estimation can be made more efficient and accurate by restricting the stimulus optimization region to the metaphysis/epiphysis. In addition, a simple method, based on the variation of diaphyseal cortical thickness, is developed for assigning the thickness to the back-plate. It is also shown that the number of columns of nodes used as multipoint constraints does not have a significant effect on the method.     

Functional adaptation of cancellous bone in human proximal femur predicted by trabecular surface remodeling simulation toward uniform stress state

Two-dimensional simulation of trabecular surface remodeling was conducted for a human proximal femur to investigate the structural change of cancellous bone toward a uniform stress state. Considering that a local mechanical stimulus plays an important role in cellular activities in bone remodeling, local stress nonuniformity was assumed to drive trabecular structural change to seek a uniform stress state. A large-scale pixel-based finite element model was used to simulate structural changes of individual trabeculae over the entire bone. As a result, the initial structure of trabeculae changed from isotropic to anisotropic due to trabecular microstructural changes caused by surface remodeling according to the mechanical environment in the proximal femur. Under a single-loading condition, it was shown that the apparent structural property evaluated by fabric ellipses corresponded to the apparent stress state in cancellous bone. As is observed in the actual bone, a distributed trabecular structure was obtained under a multiple-loading condition. Through these studies, it was concluded that trabecular surface remodeling toward a local uniform stress state at the trabecular level could naturally bring about functional adaptation phenomenon at the apparent tissue level. The proposed simulation model would be capable of providing insight into the hierarchical mechanism of trabecular surface remodeling at the microstructural level up to the apparent tissue level.     

A topology optimization based model of bone adaptation

A novel topology optimization model based on homogenization methods was developed for predicting bone density distribution and anisotropy, assuming the bone structure to be a self-optimizing biological material which maximizes its own structural stiffness. The feasibility and efficiency of this method were tested on a 2D model for a proximal femur under single and multiple loading conditions. The main aim was to compute homogenized optimal designs using an optimal laminated microstructure. The computational results showed that high bone density levels are distributed along the diaphysis and form arching struts within the femoral head. The pattern of bone density distribution and the anisotropic bone behavior predicted by the model in the multiple load case were both in good agreement with the structural architecture and bone density distribution occurring in natural femora. This approach provides a novel means of understanding the remodeling processes involved in fracture repair and the treatment of bone diseases.     

Intravoxel bone micromechanics for microCT-based finite element simulations

While micro-FE simulations have become a standard tool in computational biomechanics, the choice of appropriate material properties is still a relevant topic, typically involving empirical grey value-to-elastic modulus relations. We here derive the voxel-specific volume fractions of mineral, collagen, and water, from tissue-independent bilinear relations between mineral and collagen content in extracellular bone tissue (J. Theor. Biol. 287: 115, 2011), and from the measured X-ray attenuation information quantified in terms of grey values. The aforementioned volume fractions enter a micromechanics representation of bone tissue, as to deliver voxel-specific stiffness tensors. In order to check the relevance of this strategy, we convert a micro Computer Tomograph of a mouse femur into a regular Finite Element mesh, apply forces related to the dead load of a standing mouse, and then compare simulation results based on voxel-specific heterogeneous elastic properties to results based on homogeneous elastic properties related to the spatial average over the solid bone matrix compartment, of the X-ray attenuation coefficients. The element-specific strain energy density illustrates that use of homogeneous elastic properties implies overestimation of the organ stiffness. Moreover, the simulation reveals large tensile normal stresses throughout the femur neck, which may explain the mouse femur neck's trabecular morphology being quite different from the human case, where the femur neck bears compressive forces and bending moments.     

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.     

Computational sensitivity investigation of hydrogel injection characteristics for myocardial support

Biomaterial injection is a potential new therapy for augmenting ventricular mechanics after myocardial infarction (MI). Recent in vivo studies have demonstrated that hydrogel injections can mitigate the adverse remodeling due to MI. More importantly, the material properties of these injections influence the efficacy of the therapy. The goal of the current study is to explore the interrelated effects of injection stiffness and injection volume on diastolic ventricular wall stress and thickness. To achieve this, finite element models were constructed with different hydrogel injection volumes (150 µL and 300 µL), where the modulus was assessed over a range of 0.1 kPa to 100 kPa (based on experimental measurements). The results indicate that a larger injection volume and higher stiffness reduce diastolic myofiber stress the most, by maintaining the wall thickness during loading. Interestingly, the efficacy begins to taper after the hydrogel injection stiffness reaches a value of 50 kPa. This computational approach could be used in the future to evaluate the optimal properties of the hydrogel.     

Indirect determination of trabecular bone effective tissue failure properties using micro-finite element simulations

Trabecular bone strength is marked not only by the onset of local yielding, but also by post-yield behavior. To study and predict trabecular bone elastic and yield properties, micro-finite element (micro-FE) models were successfully applied. However, trabecular bone strength predictions require micro-FE models incorporating post-yield behavior of trabecular bone tissue. Due to experimental difficulties, such data is currently not available. Here we used micro-FE modeling to determine failure behavior of trabecular bone tissue indirectly, by iteratively fitting FE simulation to experimental results. Failure parameters were fitted to an isotropic plasticity model based on Hill's yield function, using materially and geometrically nonlinear micro-FE models of seven bovine trabecular bone specimens. The predictive value of the averaged effective tissue properties was subsequently tested. The results showed that compression softening had to be included on the tissue level in order to accurately describe the apparent-level behavior of the bone specimens. A sensitivity study revealed that the simulated response was less sensitive to variations in the post-yield properties of the bone tissue than variations in the elastic and yield properties. Due to fitting of the tissue properties, apparent-level behavior could be accurately reproduced for each specimen separately. Predictions based on the averaged and fixed tissue properties were less accurate, due to inter-specimen variations in the tissue properties.     

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.     

Long-term study of bone remodelling after femoral stem: a comparison between dexa and finite element simulation

A hip replacement with a cemented or cementless femoral stem produces an effect on the bone called adaptive remodelling, attributable to mechanical and biological factors. The objective of all of cementless prostheses designs has been to achieve a perfect transfer of loads in order to avoid stress-shielding, which produces an osteopenia. In order to quantify this, the long term and mass-produced study with dual energy X-ray absorptiometry (DEXA) is necessary. Finite element (FE) simulation makes possible the explanation of the biomechanical changes which are produced in the femur after stem implantation. The good correlation obtained between the results of the FE simulation and the densitometric study allow, on one hand, to explain from the point of view of biomechanical performance the changes observed in bone density in the long-term, where it is clear that these are due to a different transfer of load in the implanted model compared to the healthy femur; on the other hand, it validates the simulation model, in a way that it can be used in different conditions and at different time periods, to carry out a sufficiently precise prediction of the evolution of the bone density from the biomechanical behaviour in the interaction between the prosthesis and femur.     

Direct mechanics assessment of elastic symmetries and properties of trabecular bone architecture

A method is presented to find orthotropic elastic symmetries and constants directly from the elastic coefficients in the overall stiffness matrix of trabecular bone test specimens. Contrary to earlier developed techniques, this method does not require pure orthotropic behavior or additional fabric measurements. The method uses high-resolution computer reconstructions of trabecular bone specimens as input for large-scale FE-analyses to determine all the 21 elastic coefficients in the overall stiffness matrix of the specimen, using a direct mechanics approach. An optimization procedure is then used to find the coordinate transformation that yields the best orthotropic representation of this matrix. The method is illustrated here relative to two trabecular bone specimens. The techniques developed here can be used to obtain a complete characterization of the mechanical properties of trabecular architecture. With the development of in vivo reconstruction techniques, even in vivo measurements will be possible.     

Simulation of planar soft tissues using a structural constitutive model: Finite element implementation and validation

Computational implementation of physical and physiologically realistic constitutive models is critical for numerical simulation of soft biological tissues in a variety of biomedical applications. It is well established that the highly nonlinear and anisotropic mechanical behaviors of soft tissues are an emergent behavior of the underlying tissue microstructure. In the present study, we have implemented a structural constitutive model into a finite element framework specialized for membrane tissues. We noted that starting with a single element subjected to uniaxial tension, the non-fibrous tissue matrix must be present to prevent unrealistic tissue deformations. Flexural simulations were used to set the non-fibrous matrix modulus because fibers have little effects on tissue deformation under three-point bending. Multiple deformation modes were simulated, including strip biaxial, planar biaxial with two attachment methods, and membrane inflation. Detailed comparisons with experimental data were undertaken to insure faithful simulations of both the macro-level stress–strain insights into adaptations of the fiber architecture under stress, such as fiber reorientation and fiber recruitment. Results indicated a high degree of fidelity and demonstrated interesting microstructural adaptions to stress and the important role of the underlying tissue matrix. Moreover, we apparently resolve a discrepancy in our 1997 study (Billiar and Sacks, 1997. J. Biomech. 30 (7), 753–756) where we observed that under strip biaxial stretch the simulated fiber splay responses were not in good agreement with the experimental results, suggesting non-affine deformations may have occurred. However, by correctly accounting for the isotropic phase of the measured fiber splay, good agreement was obtained. While not the final word, these simulations suggest that affine fiber kinematics for planar collagenous tissues is a reasonable assumption at the macro level. Simulation tools such as these are imperative in the design and simulation of native and engineered tissues.