Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients.

Breast cancer is a significant public health issue affecting women worldwide. While advancements in treatment options have led to improved survival rates, the impact of breast cancer and its treatments on bone health cannot be overlooked. Bone remodeling is a complex process regulated by the delicate balance between bone formation and resorption. Any disruption to this balance can lead to decreased bone density, increased fracture risk, and compromised physical function. To investigate the effects of breast cancer and its treatments on bone remodeling, a finite element model was developed in this study. This model incorporated bone remodeling equations to simulate the mechanical behavior of bone under different conditions. The ABAQUS/UMAT software was used to simulate the behavior of bone tissue under the influence of breast cancer and treatments. Our findings suggest that bone loss is more pronounced after secondary breast cancer and treatment, leading to bone loss (6%-19% decrease in BV/TV), reduced bone stimulation, and decreased effectiveness of physical activity on recovery. These results highlight the importance of early intervention and management of bone health in breast cancer patients to mitigate the negative impact of cancer and treatment on bone remodeling.

Toward a Mesoscopic Modeling Approach of Magnetohydrodynamic Blood Flow in Pathological Vessels: A Comprehensive Review.

The investigation of magnetohydrodynamic (MHD) blood flow within configurations that are pertinent to the human anatomy holds significant importance in the realm of scientific inquiry because of its practical implications within the medical field. This article presents an exhaustive appraisal of the diverse applications of magnetohydrodynamics and their computational modeling in biological contexts. These applications are classified into two categories: simple flow and pulsatile flow. An alternative approach of traditional CFD methods called Lattice Boltzmann Method (LBM), a mesoscopic method based on kinetic theory, is introduced to solve complex problems, such as hemodynamics. The results show that the flow velocity reduces considerably by increasing the magnetic field intensity, and the flow separation area is minimized by the increase of magnetic field strength. The LBM with BGK collision model has shown good results in terms of precision. Finally, this literature review has revealed a number of potential avenues for further research. Suggestions for future works are proposed accordingly.

Modeling and simulation of bone cells dynamic behavior under the late effect of breast cancer treatments.

Breast Cancer (BC) treatments have been proven to interfere with the health of bones. Chemotherapy and endocrinal treatment regimens such as tamoxifen and aromatase inhibitors are frequently prescribed for women with BC. However, these drugs increase bone resorption and reduce the Bone Mineral Density (BMD), thus increasing the risk of bone fracture. In the current study, a mechanobiological bone remodeling model has been developed by coupling cellular activities, mechanical stimuli, and the effect of breast cancer treatments (chemotherapy, tamoxifen, and aromatase inhibitors). This model algorithm has been programmed and implemented on MATLAB software to simulate different treatment scenarios and their effects on bone remodeling and also predict the evolution of Bone Volume fraction (BV/TV) and the associated Bone Density Loss (BDL) over a period of time. The simulation results, achieved from different combinations of Breast Cancer treatments, allow the researchers to predict the intensity of each combination treatment on BV/TV and BMD. The combination of chemotherapy, tamoxifen, and aromatase inhibitors, followed by the combination of chemotherapy and tamoxifen remain the most harmful regimen. This is because they have a strong ability to induce the bone degradation which is represented by a decrease of 13.55% and 11.55% of the BV/TV value, respectively. These results were compared with the experimental studies and clinical observations which showed good agreement. The proposed model can be used by clinicians and physicians to choose the most appropriate combination of treatments, according to the patient's case.

Experimental-based mechanobiological modeling of the anabolic and catabolic effects of breast cancer on bone remodeling.

Bone is a biological tissue characterized by its hierarchical organization. This material has the ability to be continually renewed, which makes it highly adaptative to external loadings. Bone renewing is managed by a dynamic biological process called bone remodeling (BR), where continuous resorption of old bone and formation of new bone permits to change the bone composition and microstructure. Unfortunately, because of several factors, such as age, hormonal imbalance, and a variety of pathologies including cancer metastases, this process can be disturbed leading to various bone diseases. In this study, we have investigated the effect of breast cancer (BC) metastases causing osteolytic bone loss. BC has the ability to affect bone quantity in different ways in each of its primary and secondary stages. Based on a BR mathematical model, we modeled the BC cells' interaction with bone cells to assess their effect on bone volume fraction (BV/TV) evolution during the remodeling process. Some of the parameters used in our model have been determined experimentally using the enzyme-linked immune-sorbent assay (ELISA) and the MTT assay. Our numerical simulations show that primary BC plays a significant role in enhancing bone-forming cells' activity leading to a 6.22% increase in BV/TV over 1 year. On the other hand, secondary BC causes a noticeable decrease in BV/TV reaching 15.74% over 2 years.

Magnetohydrodynamic blood flow study in stenotic coronary artery using lattice Boltzmann method.

BACKGROUND AND OBJECTIVE: Cardiovascular diseases such as atherosclerosis are the first engender of death in the world. The malfunctioning of cardiovascular system is attributed mainly to hemodynamics. However, blood magnetic properties are of major haemodynamic interest, with significant clinical applications. The aim of this work is to study numerically the effect of high magnetic field on blood flow in stenotic artery. METHODS: In this paper, a double population D2Q9 lattice Boltzmann model is proposed. Velocity and magnetic field are both solved using Lattice Boltzmann method with single relaxation time. Blood is considered homogeneous and Newtonian bio-magnetic fluid. The results of the proposed model are compared and validated by recent numerical and experimental studies in the literature and show good agreement. In this study, simulations are carried out for both hydrodynamics and magneto-hydrodynamics. For the magneto-hydrodynamic case, five values of Hartmann number of 10, 30, 50, 75 and 100 at Reynolds number of 400, 600 and 800 are investigated Results: The results show that velocity and recirculation zone increase with the increase of the degree of stenosis and Reynolds number. In addition, a considerable decrease in velocity, recirculation zones and pressure drop across the stenotic artery is noticed with the increase of Hartmann number. CONCLUSION: The suggested model is found to be effective and accurate in the treatment of magneto-hydrodynamic blood flow in stenotic artery. The found results can be used by clinicians in the treatment of certain cardiovascular disorders and in regulating blood flow movement, especially during surgical procedures.

Is Pedicle-Based Hybrid Stabilization (PBHS) protecting posterior lumbar fixation from adjacent-segment failure? Finite element analysis and comparison of different systems.

INTRODUCTION: Interbody fusion is a very common surgical treatment for degenerative disc diseases. It is necessary to explain the effect of Pedicle Based Hybrid Stabilization systems (PBHS) on the lumbar spine, as there is no consensus in the literature about their performance. HYPOTHESIS: Topping off a fusion with a PBHS may provide some protection against adjacent segment failure. MATERIAL AND METHODS: The biomechanical effect PBHS on fused and adjacent to fusion levels were investigated, including range of motion, bending stiffness, Von Mises stress A 3D Finite Element model of the L2-S1 spine was used and modified to simulate pre and postoperative changes during combined loading. Five models instrumented with different systems [Titanium and PEEK fusion; Dynesys hybrid system; NFlex hybrid stabilization and PEEK topping off fusion] were compared to those of healthy model. RESULTS: After hybrid instrumentation, the L4-L5 level did not lose its motion completely, NFlex hybrid stabilization system maintained 82% of flexion at the adjacent to fusion level, reduced bending stiffness by 40% in axial rotation. Dynesys hybrid system represented more restricted motion than NFlex. PEEK topping off fusion system was the most rigid one among all three systems. It increased bending stiffness at the adjacent level and increased the axial motion by 25%. High risk of rod breakage was computed for PEEK topping off system as 48.8MPa in lateral bending. CONCLUSION: Hybrid stabilization can delay adjacent segment failure and compensate lumbar spine mobility. However, it is clear that PBHS need to be further tested before being considered for clinical use. LEVEL OF EVIDENCE: III; well-designed computational non-experimental study.

Toward a Mathematical Modeling of Diseases' Impact on Bone Remodeling: Technical Review.

A wide variety of bone diseases have hitherto been discovered, such as osteoporosis, Paget's disease, osteopetrosis, and metastatic bone disease, which are not well defined in terms of changes in biochemical and mechanobiological regulatory factors. Some of these diseases are secondary to other pathologies, including cancer, or to some clinical treatments. To better understand bone behavior and prevent its deterioration, bone biomechanics have been the subject of mathematical modeling that exponentially increased over the last years. These models are becoming increasingly complex. The current paper provides a timely and critical analysis of previously developed bone remodeling mathematical models, particularly those addressing bone diseases. Besides, mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, which englobe bone disease and its treatment's effect on bone health. Therefore, the review starts by presenting bone remodeling cycle and mathematical models describing this process, followed by introducing some bone diseases and discussing models of pathological mechanisms affecting bone, and concludes with exhibiting the available bone treatment procedures considered in the PK/PD models.

Biomechanical investigation of the effect of pedicle-based hybrid stabilization constructs: A finite element study.

Hybrid stabilization is widely performed for the surgical treatment of degenerative disk diseases. Pedicle-based hybrid stabilization intends to reduce fusion-associated drawbacks of adjacent segment degeneration, construct failure, and pseudoarthrosis. Recently, many types of pedicle-based hybrid stabilization systems have been developed and optimized, using polymeric devices as an adjunct for lumbar fusion procedures. Therefore, the purpose of this study was to evaluate the effect of new pedicle-based hybrid stabilization on bending stiffness and center of rotation at operated and adjacent levels in comparison with established semirigid and rigid devices in lumbar fusion procedures. A validated three-dimensional finite element model of the L3-S1 segments was modified to simulate postoperative changes during combined loading (moment of 7.5 N m + follower load of 400 N). Two models instrumented with pedicle-based hybrid stabilization (Dynesys Transition Optima, NFlex), semirigid system (polyetheretherketone), and rigid fixation system (titanium rod (Ti) were compared with those of the healthy and degenerated models. Contact force on the facet joint during extension increased in fusion (40 N) with an increase of bending stiffness in Dynesys and NFlex. The center of rotation shifted in posterior and cranial directions of the fused level. The centers of rotation in the lower lumbar spine is segment dependent and altered with the adopted construct. The bending stiffness was varied from 1.47 N m/° in lateral bending for the healthy model to 5.75 N m/° for the NFlex stabilization, which had the closest center of rotation, compared to the healthy center of rotation. Locations of center of rotation, stress, and strain distribution varied according to construct design and materials used. These data could help understand the biomechanical effects of current pedicle-based hybrid stabilization on the behavior of the lower lumbar spine.

Age-related mechanical strength evolution of trabecular bone under fatigue damage for both genders: Fracture risk evaluation.

Bone tissue is a living composite material, providing mechanical and homeostatic functions, and able to constantly adapt its microstructure to changes in long term loading. This adaptation is conducted by a physiological process, known as "bone remodeling". This latter is manifested by interactions between osteoclasts and osteoblasts, and can be influenced by many local factors, via effects on bone cell differentiation and proliferation. In the current work, age and gender effects on damage rate evolution, throughout life, have been investigated using a mechanobiological finite element modeling. To achieve the aim, a mathematical model has been developed, coupling both cell activities and mechanical behavior of trabecular bone, under cyclic loadings. A series of computational simulations (ABAQUS/UMAT) has been performed on a 3D human proximal femur, allowing to investigate the effects of mechanical and biological parameters on mechanical strength of trabecular bone, in order to evaluate the fracture risk resulting from fatigue damage. The obtained results revealed that mechanical stimulus amplitude affects bone resorption and formation rates, and indicated that age and gender are major factors in bone response to the applied loadings.

Finite element analysis of the effect of high tibial osteotomy correction angle on articular cartilage loading.

Osteoarthritis is a globally common disease that imposes a considerable ongoing health and economic burden on the socioeconomic system. As more and more biomechanical factors have been explored, malalignment of the lower limb has been found to influence the load distribution across the articular surface of the knee joint substantially. In this work, a three-dimensional finite element analysis was carried out to investigate the effect of varying the high tibial osteotomy correction angle on the stress distribution in both compartments of the human knee joint. Thereafter, determine the optimal correction angle to achieve a balanced loading between these two compartments. The developed finite element model was validated against experimental and numerical results. The findings of this work suggest that by changing the correction angle from 0° to 10° valgus, high tibial osteotomy shifted the mechanical load from the affected medial compartment to the lateral compartment with intact cartilage. The Von Mises and the shear stresses decreased in the medial compartment and increased in the lateral compartment. Moreover, a balanced stress distribution between the two compartments as well as the desired alignment were achieved under a valgus hypercorrection of 4.5° that significantly unloads the medial compartment, loads the lateral compartment and arrests the progression of osteoarthritis. After comparing the achieved results against the ones of previous studies that explored the effects of the high tibial osteotomy correction angle on either clinical outcomes or biomechanical outcomes, one can conclude that the findings of this study agree well with the related clinical data and recommendations found in the literature.

New three-dimensional model based on finite element method of bone nanostructure: single TC molecule scale level.

At the macroscopic scale, the bone mechanical behavior (fracture, elastic) depends mainly on its components' nature at the nanoscopic scale (collagen, mineral). Thus, an understanding of the mechanical behavior of the elementary components is demanded to understand the phenomena that can be observed at the macroscopic scale. In this article, a new numerical model based on finite element method is proposed in order to describe the mechanical behavior of a single Tropocollagen molecule. Furthermore, a parametric study with different geometric properties covering the molecular composition and the rate hydration influence is presented. The proposed model has been tested under tensile loading. While focusing on the entropic response, the geometric parameter variation effect on the mechanical behavior of Tropocollagen molecule has been revealed using the model. Using numerical and experimental testing, the obtained numerical simulation results seem to be acceptable, showing a good agreement with those found in literature.

Age and gender effects on bone mass density variation: finite elements simulation.

Bone remodeling is a physiological process by which bone constantly adapts its structure to changes in long-term loading manifested by interactions between osteoclasts and osteoblasts. This process can be influenced by many local factors, via effects on bone cells differentiation and proliferation, which are produced by bone cells and act in a paracrine or autocrine way. The aim of the current work is to provide mechanobiological finite elements modeling coupling both cellular activities and mechanical behavior in order to investigate age and gender effects on bone remodeling evolution. A series of computational simulations have been performed on a 2D and 3D human proximal femur. An age- and gender-related impacts on bulk density alteration of trabecular bone have been noticed, and the major actors responsible of this phenomenon have been then discussed.

A multiscale modelling of bone ultrastructure elastic proprieties using finite elements simulation and neural network method.

Bone is a living material with a complex hierarchical structure which entails exceptional mechanical properties, including high fracture toughness, specific stiffness and strength. Bone tissue is essentially composed by two phases distributed in approximately 30-70%: an organic phase (mainly type I collagen and cells) and an inorganic phase (hydroxyapatite-HA-and water). The nanostructure of bone can be represented throughout three scale levels where different repetitive structural units or building blocks are found: at the first level, collagen molecules are arranged in a pentameric structure where mineral crystals grow in specific sites. This primary bone structure constitutes the mineralized collagen microfibril. A structural organization of inter-digitating microfibrils forms the mineralized collagen fibril which represents the second scale level. The third scale level corresponds to the mineralized collagen fibre which is composed by the binding of fibrils. The hierarchical nature of the bone tissue is largely responsible of their significant mechanical properties; consequently, this is a current outstanding research topic. Scarce works in literature correlates the elastic properties in the three scale levels at the bone nanoscale. The main goal of this work is to estimate the elastic properties of the bone tissue in a multiscale approach including a sensitivity analysis of the elastic behaviour at each length scale. This proposal is achieved by means of a novel hybrid multiscale modelling that involves neural network (NN) computations and finite elements method (FEM) analysis. The elastic properties are estimated using a neural network simulation that previously has been trained with the database results of the finite element models. In the results of this work, parametric analysis and averaged elastic constants for each length scale are provided. Likewise, the influence of the elastic constants of the tissue constituents is also depicted. Results highlight that intelligent numerical methods are powerful and accurate procedures to deal with the complex multiscale problem in the bone tissue with results in agreement with values found in literature for specific scale levels.

Effect of material and structural factors on fracture behaviour of mineralised collagen microfibril using finite element simulation.

Bone is a multiscale heterogeneous material and its principal function is to support the body structure and to resist mechanical loads without fracturing. Numerical modelling of biocomposites at different length scales provides an improved understanding of the mechanical behaviour of structures such as bone, and also guides the development of multiscale mechanical models. Here, a three-dimensional nano-scale model of mineralised collagen microfibril based on the finite element method was employed to investigate the effect of material and structural factors on the mechanical equivalent of fracture properties. Fracture stress and damping capacity as functions of the number of cross-links were obtained under tensile loading conditions for different densities and Young's modulus of the mineral phase. The results show that the number of cross-links and the density of mineral as well as Young's modulus of mineral have an important influence on the strength of mineralised collagen microfibrils which in turn clarify the bone fracture on a macroscale.

Nanomechanical properties of mineralised collagen microfibrils based on finite elements method: biomechanical role of cross-links.

Hierarchical structures in bio-composites such as bone tissue have many scales or levels and synergic interactions between the different levels. They also have a highly complex architecture in order to fulfil their biological and mechanical functions. In this study, a new three-dimensional (3D) model based on the finite elements (FEs) method was used to model the relationship between the hierarchical structure and the properties of the constituents at the sub-structure scale (mineralised collagen microfibrils) and to investigate their apparent nanomechanical properties. The results of the proposed FE simulations show that the elastic properties of microfibrils depend on different factors such as the number of cross-links, the mechanical properties and the volume fraction of phases. The results obtained under compression loading at a small deformation < 2% show that the microfibrils have a Young's modulus (Ef) ranging from 0.4 to 1.16 GPa and a Poisson's ratio ranging from 0.26 to 0.3. These results are in excellent agreement with experimental data (X-ray, AFM and MEMS) and molecular simulations.

Multiscale approach including microfibril scale to assess elastic constants of cortical bone based on neural network computation and homogenization method.

The complexity and heterogeneity of bone tissue require a multiscale modeling to understand its mechanical behavior and its remodeling mechanisms. In this paper, a novel multiscale hierarchical approach including microfibril scale based on hybrid neural network (NN) computation and homogenization equations was developed to link nanoscopic and macroscopic scales to estimate the elastic properties of human cortical bone. The multiscale model is divided into three main phases: (i) in step 0, the elastic constants of collagen-water and mineral-water composites are calculated by averaging the upper and lower Hill bounds; (ii) in step 1, the elastic properties of the collagen microfibril are computed using a trained NN simulation. Finite element calculation is performed at nanoscopic levels to provide a database to train an in-house NN program; and (iii) in steps 2-10 from fibril to continuum cortical bone tissue, homogenization equations are used to perform the computation at the higher scales. The NN outputs (elastic properties of the microfibril) are used as inputs for the homogenization computation to determine the properties of mineralized collagen fibril. The mechanical and geometrical properties of bone constituents (mineral, collagen, and cross-links) as well as the porosity were taken in consideration. This paper aims to predict analytically the effective elastic constants of cortical bone by modeling its elastic response at these different scales, ranging from the nanostructural to mesostructural levels. Our findings of the lowest scale's output were well integrated with the other higher levels and serve as inputs for the next higher scale modeling. Good agreement was obtained between our predicted results and literature data.

Physically based 3D finite element model of a single mineralized collagen microfibril.

Mineralized collagen microfibrils in human bone provide its mechanical properties (stiffness, elasticity, ductility, energy dissipation and strength). However, detailed 3D finite element models describing the mechanical behavior of the mineralized collagen microfibrils are still lacking. In the current work, we developed a 3D finite element model of the mineralized collagen microfibril that incorporates the physical 3D structural details. The model components consist of five tropocollagen molecules, mineral hydroxyapatite and intermolecular cross-links joining primarily the ends of the tropocollagen molecules. Dimension, arrangement and mechanical behavior of the constituents are based on previously published experimental and theoretical data. Tensile and compressive loads were applied to the microfibril under different conditions (hydrated and dehydrated collagen) to investigate the relationship between the structure and the mechanical behavior of the mineralized collagen microfibril (stress-strain curve and elastic modulus). The computational results match the experimental available data well, and provide insight into the role of the phases and morphology on the microfibril behavior. Our predicted results show that the mechanical properties of collagen microfibrils arise due to their structure and properties. The proposed 3D finite element model of mineralized collagen microfibril contributes toward the investigation of the bottom-up structure-property relationships in human bone.

Finite element 3D modeling of mechanical behavior of mineralized collagen microfibrils.

PURPOSE: The aim of this work is to develop a 3D finite elements model to study the nanomechanical behavior of mineralized collagen microfibrils, which consists of three phases, (i) collagen phase formed by five tropocollagen (TC) molecules linked together with cross-links, (ii) a mineral phase (Hydroxyapatite), and (iii) impure mineral phase, and to investigate the important role of individual properties of every constituent. METHODS: The mechanical and geometric properties (TC molecule diameter) of both tropocollagen and mineral were taken into consideration as well as cross-links, which was represented by spring elements with adjusted properties based on experimental data. In this paper an equivalent homogenized model was developed to assess the whole microfibril mechanical properties (Young's modulus and Poisson's ratio) under varying mechanical properties of each phase. RESULTS: In this study, both equivalent Young's modulus and Poisson's ratio, which were expressed as functions of Young's modulus of each phase, were obtained under tensile load with symmetric and periodic boundary conditions.