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The present study proposes a mathematical model elucidating some aspects of the bio-mechanical stimulus involved in bone remodelling, which, in our assumptions, acts as a diffusive signalling agent for bones. The proposed mathematical model aims to scrutinize the behaviour of bone tissues and their evolution over time by better understanding the mechanisms of bone remodelling and offering new theoretical tools for developing more effective and efficient treatment strategies for bone defects, trauma, or diseases. The bone remodelling process involves adapting bone mechanical properties in response to dynamic loads. This adaptation is achieved through the diffusive stimulus created by these loads. The result is a functional adaptation of the bone, wherein it acquires the mechanical properties required to withstand the loads to which it is subjected. This phenomenon has significant implications for the study of bone physiology and biomechanics. As such, it is a topic of great interest to researchers and practitioners in the fields of orthopaedics, sports medicine, and related disciplines. In this contribution, the mechanical behaviour is modelled through a generalized three-dimensional deformable continuum that also takes into account the porous nature of the bone tissue with a nonlinear constitutive law. Since we have focused the study on the model of the stimulus and its interplay with the evolution of the tissue, an isotropic material symmetry is adopted to simplify the problem. This formulation is promising because it permits the bone tissue to evolve depending on the time variability of the external mechanical loads, even if the source of the stimulus is assumed to be the strain energy density. The proposed model exhibits great potential, and its scope extends to several other applications, including the integration of anisotropic material symmetry and damage. Further research in this area can unlock new possibilities and enable the development of more advanced models with these new features. We plan future investigations to focus on these areas to exploit the full potential of this model entirely. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) increases fracture incidence and fracture-related mortality rates (KK.Cg-Ay/J. The Jackson Laboratory; Available from: https://www.jax.org/strain/002468). While numerous mouse models for T2D exist, few effectively stimulate persistent hyperglycemia in both sexes, and even fewer are suitable for bone studies. Commonly used models like db/db and ob/ob have altered leptin pathways, confounding bone-related findings since leptin regulates bone properties (Fajardo et al. in Journal of Bone and Mineral Research 29(5): 1025–1040, 2014). The Yellow Kuo Kondo (KK/Ay) mouse, a polygenic mutation model of T2D, is able to produce a consistent diabetic state in both sexes and addresses the lack of a suitable model of T2D for bone studies. The diabetic state of KK/Ay stems from a mutation in the agouti gene, responsible for coat color in mice. This mutation induces ectopic gene expression across various tissue types, resulting in diabetic mice with yellow fur coats (Moussa and Claycombe in Obesity Research 7(5): 506–514, 1999). Male and female KK/Ay mice exhibited persistent hyperglycemia, defining them as diabetic with blood glucose (BG) levels consistently exceeding 300 mg/dL. Notably, male control mice in this study were also diabetic, presenting a significant limitation. Nevertheless, male and female KK/Ay mice showed significantly elevated BG levels, HbA1c, and serum insulin concentration when compared to the non-diabetic female control mice. Early stages of T2D are characterized by hyperglycemia and hyperinsulinemia resulting from cellular insulin resistance, whereas later stages may feature hypoinsulinemia due to β-cell apoptosis (Banday et al. Avicenna Journal of Medicine 10(04): 174–188, 2020 and Klein et al. Cell Metabolism 34(1): 11–20, 2022). The observed hyperglycemia, hyperinsulinemia, and the absence of differences in β-cell mass suggest that KK/Ay mice in this study are modeling the earlier stages of T2D. While compromised bone microarchitecture was observed in this study, older KK/Ay mice, representing more advanced stages of T2D, might exhibit more pronounced skeletal manifestations. Compared to the control group, the femora of KK/Ay mice had higher cortical area and cortical thickness, and improved trabecular properties which would typically be indicative of greater bone strength. However, KK/Ay mice displayed lower cortical tissue mineral density in both sexes and increased cortical porosity in females. Fracture instability toughness of the femora was lower in KK/Ay mice overall compared to controls. These findings indicate that decreased mechanical integrity noted in the femora of KK/Ay mice was likely due to overall bone quality being compromised. [ABSTRACT FROM AUTHOR]

Finite element analysis (FEA) is commonly used in orthopaedic research to estimate localised tissue stresses and strains. A variety of boundary conditions have been proposed for isolated femur analysis, but it remains unclear how these assumed constraints influence FEA predictions of bone biomechanics. This study compared the femoral head deflection (FHD), stresses, and strains elicited under four commonly used boundary conditions (fixed knee, mid-shaft constraint, springs, and isostatic methods) and benchmarked these mechanics against the gold standard inertia relief method for normal and pathological femurs (extreme anteversion and retroversion, coxa vara, and coxa valga). Simulations were performed for the stance phase of walking with the applied femoral loading determined from patient-specific neuromusculoskeletal models. Due to unrealistic biomechanics observed for the commonly used boundary conditions, we propose a novel biomechanical constraint method to generate physiological femur biomechanics. The biomechanical method yielded FHD (< 1 mm), strains (approaching 1000 µε), and stresses (< 60 MPa), which were consistent with physiological observations and similar to predictions from the inertia relief method (average coefficient of determination = 0.97, average normalized root mean square error = 0.17). Our results highlight the superior performance of the biomechanical method compared to current methods of constraint for both healthy and pathological femurs. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HAP) constitutes the primary mineral component of bones, and its crystal structure, along with the surface interaction with proteins, significantly influences the outstanding mechanical properties of bone. This study focuses on natural hydroxyapatite, constructing a surface model with calcium vacancy defects. Employing a representative model of aspartic acid residues, we delve into the adsorption mechanism on the crystal surface and scrutinize the adsorption forms of amino acid residues on HAP and calcium-deficient hydroxyapatite (CDHA) surfaces. The research also explores the impact of different environments on adsorption energy. Furthermore, a simplified sandwich structure of crystal-polypeptide-crystal is presented, analyzing the distribution of amino acid residue adsorption sites on the crystal surface of the polypeptide fragment. This investigation aims to elucidate how the stick–slip mechanism of polypeptide molecules on the crystal surface influences the mechanical properties of the system. By uncovering the interface mechanical behavior between HAP and osteopontin peptides, this article offers valuable theoretical insights for the construction and biomimetic design of biocomposites. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether the whole-body bone Single Photon Emission Computed Tomography (SPECT) recording times of around 10 min, routinely provided by a high-sensitivity 360° cadmium and zinc telluride (CZT) camera, can be further reduced by a deep-learning noise reduction (DLNR) algorithm. Methods: DLNR was applied on whole-body images recorded after the injection of 545 ± 33 MBq of [99mTc]Tc-HDP in 19 patients (14 with bone metastasis) and reconstructed with 100%, 90%, 80%, 70%, 60%, 50%, 40%, and 30% of the original SPECT recording times. Results: Irrespective of recording time, DLNR enhanced the contrast-to-noise ratios and slightly decreased the standardized uptake values of bone lesions. Except in one markedly obese patient, the quality of DLNR processed images remained good-to-excellent down to 60% of the recording time, corresponding to around 6 min SPECT-recording. Conclusion: Ultra-fast SPECT recordings of 6 min can be achieved when DLNR is applied on whole-body bone 360° CZT-SPECT. [ABSTRACT FROM AUTHOR]

Previous findings indicated that the laser photobiomodulation is more effective than the control or placebo in preserving the alveolar socket. This study aimed to compare two different lasers regarding their effectiveness in aiding alveolar socket preservation. Twenty extraction sockets were selected then divided into two equal groups. Group A was exposed to 650 nm Diode laser, and Group B to 810 nm Diode laser following the same protocol and parameters after a standard alveolar socket preservation procedure with collagen plug. Radiographic analysis with cone beam computed tomography was done to compare the alveolar bone surface area immediately after extraction and three months post-operatively, while bone samples collected before implant drilling were histologically examined for newly formed bone evaluation and histomorphometric analysis in terms of percentage of new bone surface area, percentage of unmineralized bone and finally, immunohistochemical analysis of Osteocalcin reaction surface area as well as optical density. Radiographically, infrared (810 nm) Diode effect on alveolar bone surface area has significantly exceeded the red laser, while histologically, red (650 nm) Diode has demonstrated statistical significance regarding all parameters; newly formed bone surface area percentage, unmineralized bone area percentage and finally Osteocalcin bone marker reaction surface area percentage and optical density. Under the specified conditions and laser parameters, photobiomodulation using the 810 nm Diode got the upper hand radiographically, yet histologically, the red 650 nm Diode managed to dominate all histological parameters when both employed as an adjunct to alveolar socket preservation procedures. [ABSTRACT FROM AUTHOR]

Nowadays, the design of porous bone scaffolds represents a crucial issue in orthopedical applications. In this article, the mechanical properties of a multi-component scaffold with different porosity percentages were investigated. Mori–Tanaka equations were used to estimate various properties of calcium phosphate (CaP) bone cement reinforced by strontium nitrate nanoparticles (NPs) based on porosity percentages in both cases; before and after samples placement in simulated body fluid (SBF) solution. With the support of these equations, the mechanical properties of bone cement material without porosity were estimated to be used in finite element analysis (FEA); so then to assess structural stability and stress distribution, the experimental compression tests on the scaffold were simulated with the ABAQUS engineering package. The mechanical properties observation indicates that the grain and particle size increased by nitrate addition to the bone cement. The approach in this manuscript allows quantifying the effect of porosity on mechanical properties of CaP cements reinforced by the strontium nitrate NPs, to be fabricated based on the patient's needs. [ABSTRACT FROM AUTHOR]

The effects of physiological and pathogenic factors on the crystal structure of calcium hydroxyapatite Ca10(PO4)6(OH)2 in mineralized bone tissues are considered. The unit cell constants of bioapatite, the unit cell deformation, and the crystallite sizes in different groups of bone tissues were analyzed based on the results of X-ray diffraction studies. The main mechanisms responsible for spatial-temporal changes in bone nanostructures were revealed. It was demonstrated that, along with violations of the stoichiometry, an important role is played by the crystallite sizes, estimated as the coherent scattering regions, the number of atoms in which differs by more than two orders of magnitude, and electrostatic interactions between the unbalanced charges of nanocrystallites and hydrated nanolayers of the mineral matrix. [ABSTRACT FROM AUTHOR]

Exercise and physical activity exert mechanical loading on the bones which induces bone formation. However, the relationship between the osteocyte lacunar-canalicular morphology and mechanical stress experienced locally by osteocytes transducing signals for bone formation is not fully understood. In this study, we used computational modeling to predict the effect of canalicular density, the number of fluid inlets, and load direction on fluid flow shear stress (FFSS) and bone strains and how these might change following the microstructural deterioration of the lacunar-canalicular network that occurs with aging. Four distinct computational models were initially generated of osteocytes with either ten or eighteen dendrites using a fluid–structure interaction method with idealized geometries. Next, a young and a simulated aged osteocyte were developed from confocal images after FITC staining of the femur of a 4-month-old C57BL/6 mouse to estimate FFSS using a computational fluid dynamics approach. The models predicted higher fluid velocities in the canaliculi versus the lacunae. Comparison of idealized models with five versus one fluid inlet indicated that with four more inlets, one-half of the dendrites experienced FFSS greater than 0.8 Pa, which has been associated with osteogenic responses. Confocal image-based models of real osteocytes indicated a six times higher ratio of canalicular to lacunar surface area in the young osteocyte model than the simulated aged model and the average FFSS in the young model (FFSS = 0.46 Pa) was three times greater than the aged model (FFSS = 0.15 Pa). Interestingly, the surface area with FFSS values above 0.8 Pa was 23 times greater in the young versus the simulated aged model. These findings may explain the impaired mechano-responsiveness of osteocytes with aging. [ABSTRACT FROM AUTHOR]

Osteocytes form a cellular network by gap junctions between their cell processes. This network is important since intercellular communication via the network is essential for bone metabolism. However, the factors that influence the formation of this osteocyte network remain unknown. As the early stage of osteocyte network formation occurs on the bone surface, we observed a newly formed trabecular bone surface by orthogonal focused ion beam-scanning electron microscopy. The embedding late osteoblast processes tended to avoid bundled collagen fibrils and elongate into sparse collagen fibrils. Then, we examined whether the inhibition of bundling of collagen fibrils using a potent lysyl oxidase inhibitor, β-aminopropionitrile (BAPN) changed the cellular network of the chick calvaria. The osteocyte shape of the control group was spindle-shape, while that of the BAPN group was sphere-shaped. In addition, the osteocyte processes of the control group were elongated vertically to the long axis of the cell body, whereas the osteocyte processes of the BAPN group were elongated radially. Therefore, it was suggested that the bundling of collagen fibrils influences normal osteocyte network formation during bone modeling. [ABSTRACT FROM AUTHOR]

Bone quality is commonly used to diagnose bone diseases such as osteoporosis, with many studies focusing on microarchitecture for fracture prediction. In this study a bovine distal femur was imaged using both micro-computed tomography (µCT) and tomosynthesis using focal construct geometry (FCG) for comparison of microarchitectural parameters. Six regions of interest (ROIs) were compared between the two imaging modalities, with both global and adaptive methods used to binarize the images. FCG images were downsampled to the same pixel size as the µCT images. Bone morphometrics were determined using BoneJ, for each imaging modality, binarization technique and ROI. Bone area/total area was found to have few significant differences between FCG and µCT (p < 0.05 for two of six ROIs). Fractal Dimension had only one significant difference (p < 0.05 for one of six ROIs) between µCT and downsampled FCG (where pixel size was equalized). Trabecular thickness and trabecular spacing were observed to follow trends as observed for the corresponding µCT images, although many absolute values were significantly different (p < 0.05 for between one and six ROIs depending on image types used). This study demonstrates the utility of tomosynthesis for measurement of microarchitectural morphometrics. [ABSTRACT FROM AUTHOR]

A comprehensive study of deformation and destruction of compact bone tissue was carried out. Deformation of cylindrical samples was carried out in the mode of constant feed rate of the press plunger. During the experiments, deformation, changes in photon radiation on the surface of the samples and acoustic emission were recorded. It is shown that the initial accumulation of stresses on the relative axis of deformation for the occurrence of a crack on the lateral surface of the sample is the first link in the chain of formation of the micro-cut plane and an indicator of its orientation relative to the axis of the cylinder. The incipient plane of a macro-crack is a zone of increased local stresses, which stimulates the appearance of new microcracks in it. In this case, the exit of the microcrack to the lateral surface of the sample of compact bone tissue (human tibia) coincides in time with the registration of photoluminescence. [ABSTRACT FROM AUTHOR]

Iron overload negatively affects bone mass and strength. However, the impact of iron excess on osteocytes—important bone cells for mechanotransduction and remodeling—is poorly understood. Herein, we examined the effects of iron exposure on osteocytes during their maturation process. We discovered that iron overload caused apoptosis of osteocytes in early and late stages of differentiation. Notably, the expression of key proteins for iron entry was downregulated during differentiation, suggesting that mature osteocytes were less susceptible to iron toxicity due to limited iron uptake. Furthermore, iron overload also enriched a subpopulation of mature osteocytes, as indicated by increased expression of Dmp1, a gene encoding protein for bone mineralization. These iron-exposed osteocytes expressed high levels of Sost, Tnfsf11 and Fgf23 transcripts. Consistently, we demonstrated that exogenous FGF23 stimulated the formation and survival of osteoclasts, suggesting its regulatory role in bone resorption. In addition, iron overload downregulated the expression of Cx43, a gene encoding gap junction protein in the dendritic processes, and impaired YAP1 nuclear translocation in response to fluid flow in differentiated osteocytes. It can be concluded that iron overload induces cellular adaptation in differentiating osteocytes, resulting in insensitivity to mechanical stimulation and potential disruption of the balance in bone remodeling. [ABSTRACT FROM AUTHOR]

We propose a variational approach that employs a generalized principle of virtual work to estimate both the mechanical response and the changes in living bone tissue during the remodeling process. This approach provides an explanation for the adaptive regulation of the bone substructure in the context of orthotropic material symmetry. We specifically focus upon the crucial gradual adjustment of bone tissue as a structural material that adapts its mechanical features, such as materials stiffnesses and microstructure, in response to the evolving loading conditions. We postulate that the evolution process relies on a feedback mechanism involving multiple stimulus signals. The mechanical and remodeling behavior of bone tissue is clearly a complex process that is difficult to describe within the framework of classical continuum theories. For this reason, a generalized continuum elastic theory is employed as a proper mathematical context for an adequate description of the examined phenomenon. To simplify the investigation, we considered a two-dimensional problem. Numerical simulations have been performed to illustrate bone evolution in a few significant cases: the bending of a rectangular cantilever plate and a three-point flexure test. The results are encouraging because they can replicate the optimization process observed in bone remodeling. The proposed model provides a likely distribution of stiffnesses and accurately represents the arrangement of trabeculae macroscopically described by the orthotropic symmetry directions, as supported by experimental evidence from the trajectorial theory. [ABSTRACT FROM AUTHOR]

NiTi is a class of metallic biomaterials, benefit from superelastic behavior, high biocompatibility, and favorable mechanical properties close to that of bone. However, the Ni ion leaching, poor bioactivity, and antibacterial activity limit its clinical applications. In this study, HAp-Nb2O5 composite layers were PC electrodeposited from aqueous electrolytes containing different concentrations of the Nb2O5 particles, i.e., 0–1 g/L, to evaluate the influence of the applied surface engineering strategy on in vitro immersion behavior, Ni2+ ion leaching level, and antibacterial activity of the bare NiTi. Surface characteristics of the electrodeposited layers were analyzed using SEM, TEM, XPS, and AFM. The immersion behavior of the samples was comprehensively investigated through SBF and long-term PBS soaking. Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) infective reference bacteria were employed to address the antibacterial activity of the samples. The results illustrated that the included particles led to more compact and smoother layers. Unlike bare NiTi, composite layers stimulated apatite formation upon immersion in both SBF and PBS media. The concentration of the released Ni2+ ion from the composite layer, containing 0.50 g/L Nb2O5 was ≈ 60% less than that of bare NiTi within 30 days of immersion in the corrosive PBS solution. The Nb2O5-reinforced layers exhibited high anti-adhesive activity against both types of pathogenic bacteria. The hybrid metallic-ceramic system comprising HAp-Nb2O5-coated NiTi offers the prospect of a potential solution for clinical challenges facing the orthopedic application of NiTi. [ABSTRACT FROM AUTHOR]

Introduction: Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. Materials and Methods: This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. Results: ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. Conclusion: Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study. [ABSTRACT FROM AUTHOR]

Introduction: The discrepancy between bone mineral density (BMD), the gold standard for bone assessment, and bone strength is a constraint in diagnosing bone function and determining treatment strategies for several bone diseases. Gastric hypochlorhydria induced by clinically used proton pump inhibitor (PPI) therapy indicates a discordance between changes in BMD and bone strength. Here, we used Cckbr-deficient mice with gastric hypochlorhydria to examine the effect of gastric hypochlorhydria on bone mass, BMD, and preferential orientation of the apatite crystallites, which is a strong indicator of bone strength. Materials and methods: Cckbr-deficient mice were created, and their femurs were analyzed for BMD and preferential orientation of the apatite c-axis along the femoral long axis. Results: Cckbr-deficient mouse femurs displayed a slight osteoporotic bone loss at 18 weeks of age; however, BMD was comparable to that of wild-type mice. In contrast, apatite orientation in the femur mid-shaft significantly decreased from 9 to 18 weeks. To the best of our knowledge, this is the first report demonstrating the deterioration of apatite orientation in the bones of Cckbr-deficient mice. Conclusion: Lesions in Cckbr-deficient mice occurred earlier in apatite orientation than in bone mass. Hence, bone apatite orientation may be a promising method for detecting hypochlorhydria-induced osteoporosis caused by PPI treatment and warrants urgent clinical applications. [ABSTRACT FROM AUTHOR]

This paper studies the feasibility of a deep neural network (DNN) approach for bone fracture diagnosis based on the non-invasive propagation of radio frequency waves. In contrast to previous "semi-automated" techniques, where X-ray images were used as the network input, in this work, we use S-parameters profiles for DNN training to avoid labeling and data collection problems. Our designed network can simultaneously classify different complex fracture types (normal, transverse, oblique, and comminuted) and estimate the length of the cracks. The proposed system can be used as a portable device in ambulances, retirement houses, and low-income settings for fast preliminary diagnosis in emergency locations when expert radiologists are not available. Using accurate modeling of the human body as well as changing tissue diameters to emulate various anatomical regions, we have created our datasets. Our numerical results show that our design DNN is successfully trained without overfitting. Finally, for the validation of the numerical results, different sets of experiments have been done on the sheep femur bones covered by the liquid phantom. Experimental results demonstrate that fracture types can be correctly classified without using potentially harmful and ionizing X-rays. [ABSTRACT FROM AUTHOR]

NiTi is a class of metallic biomaterials, benefit from superelastic behavior, high biocompatibility, and favorable mechanical properties close to that of bone. However, the Ni ion leaching, poor bioactivity, and antibacterial activity limit its clinical applications. In this study, HAp-Nb2O5 composite layers were PC electrodeposited from aqueous electrolytes containing different concentrations of the Nb2O5 particles, i.e., 0–1 g/L, to evaluate the influence of the applied surface engineering strategy on in vitro immersion behavior, Ni2+ ion leaching level, and antibacterial activity of the bare NiTi. Surface characteristics of the electrodeposited layers were analyzed using SEM, TEM, XPS, and AFM. The immersion behavior of the samples was comprehensively investigated through SBF and long-term PBS soaking. Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) infective reference bacteria were employed to address the antibacterial activity of the samples. The results illustrated that the included particles led to more compact and smoother layers. Unlike bare NiTi, composite layers stimulated apatite formation upon immersion in both SBF and PBS media. The concentration of the released Ni2+ ion from the composite layer, containing 0.50 g/L Nb2O5 was ≈ 60% less than that of bare NiTi within 30 days of immersion in the corrosive PBS solution. The Nb2O5-reinforced layers exhibited high anti-adhesive activity against both types of pathogenic bacteria. The hybrid metallic-ceramic system comprising HAp-Nb2O5-coated NiTi offers the prospect of a potential solution for clinical challenges facing the orthopedic application of NiTi. [ABSTRACT FROM AUTHOR]

Bone remodeling is an extraordinarily complex process involving a variety of factors, such as genetic, metabolic, and environmental components. Although genetic factors play a particularly important role, many have not been identified. In this study, we investigated the role of transmembrane 161a (Tmem161a) in bone structure and function using wild-type (WT) and Tmem161a-depleted (Tmem161aGT/GT) mice. Mice femurs were examined by histological, morphological, and bone strength analyses. Osteoblast differentiation and mineral deposition were examined in Tmem161a-overexpressed, -knockdown and -knockout MC3T3-e1 cells. In WT mice, Tmem161a was expressed in osteoblasts of femurs; however, it was depleted in Tmem161aGT/GT mice. Cortical bone mineral density, thickness, and bone strength were significantly increased in Tmem161aGT/GT mice femurs. In MC3T3-e1 cells, decreased expression of alkaline phosphatase (ALP) and Osterix were found in Tmem161a overexpression, and these findings were reversed in Tmem161a-knockdown or -knockout cells. Microarray and western blot analyses revealed upregulation of the P38 MAPK pathway in Tmem161a-knockout cells, which referred as stress-activated protein kinases. ALP and flow cytometry analyses revealed that Tmem161a-knockout cells were resistant to oxidative stress. In summary, Tmem161a is an important regulator of P38 MAPK signaling, and depletion of Tmem161a induces thicker and stronger bones in mice. [ABSTRACT FROM AUTHOR]

Enzymatic cross-linking of the bone collagen is important to resist to crack growth and to increased flexural strength. In the present study, we proposed a new method for assessment of enzymatic cross-link based on Fourier transform infrared (FTIR) microspectroscopy that takes into account secondary structure of type I collagen. Briefly, femurs were collected from sham or ovariectomized mice and subjected either to high-performance liquid chromatography—mass spectrometry or embedded in polymethylmethacrylate, cut and analyzed by FTIR microspectroscopy. FTIR acquisition was recorded before and after ultraviolet (UV) exposure or acid treatment. In addition, femurs from a second animal study were used to compare gene expression of Plod2 and Lox enzymes and enzymatic cross-links determined by FTIR microspectroscopy. We evidenced here that intensities and areas of subbands located at ~1660, ~1680, and ~1690 cm−1 were positively and significantly associated with the concentration of pyridinoline (PYD), deoxypyridinoline, or immature dihydroxylysinonorleucine/hydroxylysinonorleucine cross-links. Seventy-two hours exposure to UV light significantly reduced by ~86% and ~89% the intensity and area of the ~1660 cm−1 subband. Similarly, 24 h of acid treatment significantly reduced by 78% and 76% the intensity and area of the ~1690 cm−1 subband. Plod2 and Lox expression were also positively associated to the signal of the ~1660 and ~1690 cm−1 subbands. In conclusion, our study provided a new method for decomposing the amide I envelope of bone section that positively correlates with PYD and immature collagen cross-links. This method allows for investigation of tissue distribution of enzymatic cross-links in bone section. [ABSTRACT FROM AUTHOR]

Three-dimensional printing and casting materials were analyzed by prompt gamma-ray activation analysis (PGAA) to determine their suitability as human tissue surrogates for the fabrication of phantoms for medical imaging and radiation dosimetry applications. Measured elemental compositions and densities of five surrogate materials simulating soft tissue and bone were used to determine radiological properties (x-ray mass attenuation coefficient and electron stopping power). When compared with radiological properties of International Commission on Radiation Units and Measurements (ICRU) materials, it was determined that urethane rubber and PLA plastic yielded the best match for soft tissue, while silicone rubber and urethane resin best simulated the properties of bone. [ABSTRACT FROM AUTHOR]

Physical exercise is important for musculoskeletal development during puberty, which builds bone mass foundation for later in life. However, strenuous levels of training might bring adverse effects to bone health, reducing longitudinal bone growth. Animal models with various levels of physical exercise were largely used to provide knowledge to clinical settings. Experiments from our previous studies applied different levels of mechanical loading on rat tibia during puberty accompanied by weekly in vivo micro-CT scans. In the present article, we apply 3D image registration-based methods to retrospectively analyze part of the previously acquired micro-CT data. Longitudinal bone growth, growth plate thickness, and cortical bone (re)modeling were evaluated from rats' age of 28–77 days. Our results show that impact loading inhibited proximal bone growth throughout puberty. We hypothesize that impact loading might bring different growth alterations to the distal and proximal growth plates. High impact loading might lead to pathological consequence of osteochondrosis and catch-up growth due to growth inhibition. Impact loading also increased cortical bone (re)modeling before and after the peak proximal bone growth period of young rats, of which the latter case might be caused by the shift from modeling to remodeling as the dominant activity toward the end of rat puberty. We confirm that the tibial endosteum is more mechano-sensitive than the periosteum in response to mechanical loading. To our knowledge, this is the first study to follow up bone growth and bone (re)modeling of young rats throughout the entire puberty with a weekly time interval. [ABSTRACT FROM AUTHOR]

In knee arthroplasty, implants are used to replace the articulating surfaces of the tibia and femur bones, with most constituting of solid metallic components. Consequentially, biomechanical stresses and strains are no longer adequately distributed at the joint post-surgery, preventing beneficial bone remodeling. To mitigate this studies have explored additively manufacturing implants with porous lattice structures to match the mechanical properties of bone. Authors have also outlined how such structures can be designed using computed tomography data to simulate the stiffness of individuals' bones. Such methods however currently require substantial manual work by trained professionals to process the image files, extract the density information, and design lattice structures. This study proposes what is believed to be the first fully automatic pipeline capable of producing tibial trays with compliant structures customized specifically for individuals' bones, achieved using machine learning methods. The novel process, combining classification, object detection, and segmentation machine learning models, used to facilitate the automated workflow, is outlined. The efficaciousness of the pipeline is then demonstrated by testing it using clinical computed tomography data and comparing the results with those obtained manually. As a proof of concept, prototype designs generated by the pipeline with differing degrees of complexity, up to and including mapping stiffness variation in 3D through the shaft of the tibia, were also fabricated. [ABSTRACT FROM AUTHOR]

Objectives: Synthetic bone substitutes which can be adapted preoperatively and patient specific may be helpful in various bony defects in the field of oral- and maxillofacial surgery. For this purpose, composite grafts made of self-setting and oil-based calcium phosphate cement (CPC) pastes, which were reinforced with 3D-printed polycaprolactone (PCL) fiber mats were manufactured. Materials and methods: Bone defect models were acquired using patient data from real defect situations of patients from our clinic. Using a mirror imaging technique, templates of the defect situation were fabricated via a commercially available 3D-printing system. The composite grafts were assembled layer by layer, aligned on top of these templates and fitted into the defect situation. Besides, PCL-reinforced CPC samples were evaluated regarding their structural and mechanical properties via X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM), and 3-point-bending testing. Results: The process sequence including data acquisition, template fabrication, and manufacturing of patient specific implants proved to be accurate and uncomplicated. The individual implants consisting mainly of hydroxyapatite and tetracalcium phosphate displayed good processability and a high precision of fit. The mechanical properties of the CPC cements in terms of maximum force and stress load to material fatigue were not negatively affected by the PCL fiber reinforcement, whereas clinical handling properties increased remarkably. Conclusion: PCL fiber reinforcement of CPC cements enables the production of very freely modelable three-dimensional implants with adequate chemical and mechanical properties for bone replacement applications. Clinical relevance: The complex bone morphology in the region of the facial skull often poses a great challenge for a sufficient reconstruction of bony defects. A full-fledged bone replacement here often requires the replication of filigree three-dimensional structures partly without support from the surrounding tissue. With regard to this problem, the combination of smooth 3D-printed fiber mats and oil-based CPC pastes represents a promising method for fabricating patient specific degradable implants for the treatment of various craniofacial bone defects. [ABSTRACT FROM AUTHOR]

Bone drilling is a universal procedure in orthopaedics for fracture fixation, installing implants, or reconstructive surgery. Surgical drills are subjected to wear caused by their repeated use, thermal fatigue, irrigation with saline solution, and sterilization process. Wear of the cutting edges of a drill bit (worn drill) is detrimental for bone tissues and can seriously affect its performance. The aim of this study is to move closer to minimally invasive surgical procedures in bones by investigating the effect of wear of surgical drill bits on their performance. The surface quality of the drill was found to influence the bone temperature, the axial force, the torque and the extent of biological damage around the drilling region. Worn drill produced heat above the threshold level related to thermal necrosis at a depth equal to the wall thickness of an adult human bone. Statistical analysis showed that a sharp drill bit, in combination with a medium drilling speed and drilling at shallow depth, was favourable for safe drilling in bone. This study also suggests the further research on establishing a relationship between surface integrity of a surgical drill bit and irreversible damage that it can induce in delicate tissues of bone using different drill sizes as well as drilling parameters and conditions. [ABSTRACT FROM AUTHOR]

Thermoneutral housing and Raloxifene (RAL) treatment both have potential for improving mechanical and architectural properties of bone. Housing mice within a 30 to 32 °C range improves bone quality by reducing the consequences of cold stress, such as shivering and metabolic energy consumption (Chevalier et al. in Cell Metab 32(4):575–590.e7, 2020; Martin et al. in Endocr Connect 8(11):1455–1467, 2019; Hankenson et al. in Comp Med 68(6):425–438, 2018). Previous work suggests that Raloxifene can enhance bone strength and geometry (Ettinger et al. in Jama 282(7):637–645, 1999; Powell et al. in Bone Rep 12:100246, 2020). An earlier study in our lab utilized long bones to examine the effect of thermoneutral housing and Raloxifene treatment in mice, but no significant interactive effects were found. The lack of an impact is hypothesized to be connected to the short 6-week duration of the study and the type of bone analyzed. This study will examine the same question within the axial skeleton, which has a higher proportion of trabecular bone. After 6 weeks of treatment with RAL, vertebrae from female C57BL/6 J mice underwent microcomputed tomography (μCT), architectural analysis, and compression testing. Most of the tested geometric properties (bone volume/tissue volume percent, trabecular thickness, trabecular number, trabecular spacing) improved with both the housing and RAL treatment. The effect sizes suggested an additive effect when treating mice housed under thermoneutral conditions. While ultimate force was enhanced with the treatment and housing, force normalized by bone volume fraction was not significantly different between groups. For longer pre-clinical trials, it may be important to consider the impacts of temperature on mice to improve the accuracy of these models. [ABSTRACT FROM AUTHOR]

Due to the difficulty of consolidation, the risk of fractures, and the high cost of therapy, the orthopedic field views the restoration of bony defects or post-traumatic diseases as a significant issue. In recent years, efforts have been made toward guided bone regeneration as a viable solution. In this study, natural rubber latex (NRL) and latex–collagen (NRL-COL) membranes were developed and characterized, and their effects on bone regeneration in rat tibial lesions were assessed. According to the physicochemical findings, the hydrolyzed COL was effectively incorporated into the NRL membrane to produce a more robust membrane (348% increase in stress) and showed good biocompatibility for human dermal fibroblast cells and in hemolytic activity assay. According to bone analysis using computed microtomography, a substantial difference in bone volume (BV) was found among NRL, control (CONT), and NRL-COL. NRL-COL exhibited the greatest value for the bone volume/total volume ratio (BV/TV). The presence of NRL and COL was significant for the analysis of BV and BV/TV, respectively. All the experimental groups demonstrated a higher bone quality and fracture resistance, as shown by the mechanical properties of the bone. In the COL group, both neoformation of bone and total collagen levels were greater, indicating that treated defects had been closed and mature bone cells were present. Due to its angiogenic properties and the low cost of NRL membrane production, the NRL-COL membrane could be a good substitute for upcoming bone regeneration applications. [ABSTRACT FROM AUTHOR]

Cortical bone is a complex hierarchical structure consisting of biological fiber composites with transversely isotropic constituents, whose microstructures deserve extensive study to understand the mechanism of living organisms and explore development of biomimetic materials. Based on this, we establish a three-level hierarchical structure from microscale to macroscale and propose a multiscale micromechanics model of cortical bone, which considers Haversian canal, osteonal lamellae, cement line and interstitial lamellae. In order to study the microstructural effect on the elastic behavior of hierarchical structures, the Mori–Tanaka model and locally exact homogenization theory are introduced for the homogenization of heterogeneous materials of microstructure at each level. Within sub-microscale, Haversian canal and Osteonal lamella are treated as fiber and matrix, whose homogenization is surrounded with cement line matrix in microstructure (or what we called "osteon") for the second homogenization; finally, osteon and interstitial lamella establish the meso-structure for the third homogenization, predicting the effective moduli of cortical bone. The correctness of the model in this paper is verified against the data in literature with good agreement. Finally, the dynamic viscoelastic response of cortical bones is investigated from a multiscale perspective, where the measured data are substituted into the present models to study the hydration and aging effect on bones' stiffness and viscoelasticity. It is demonstrated that the hydration is much more influential in affecting the storage and loss moduli of cortical bone than the aging effect. We also present a few numerical investigations on microstructural material and geometric parameters on the overall mechanical properties of cortical bone. [ABSTRACT FROM AUTHOR]

Intrafibrillar mineralization plays a critical role in attaining desired mechanical properties of bone. It is well known that amorphous calcium phosphate (ACP) infiltrates into the collagen through the gap regions, but its underlying driving force is not understood. Based on the authors' previous observations that a collagen fibril has higher piezoelectricity at gap regions, it was hypothesized that the piezoelectric heterogeneity of collagen helps ACP infiltration through the gap. To further examine this hypothesis, the collagen piezoelectricity of osteogenesis imperfecta (OI), known as brittle bone disease, is characterized by employing Piezoresponse Force Microscopy (PFM). The OI collagen reveals similar piezoelectricity between gap and overlap regions, implying that losing piezoelectric heterogeneity in OI collagen results in abnormal intrafibrillar mineralization and, accordingly, losing the benefit of mechanical heterogeneity from the fibrillar level. This finding suggests a perspective to explain the ACP infiltration, highlighting the physiological role of collagen piezoelectricity in intrafibrillar mineralization. Piezoresponse force microscopy reveals abnormal piezoelectric and mechanical properties of collagen fibrils in brittle bone disease, highlighting the importance of collagen piezoelectricity in intrafibrillar mineralization. [ABSTRACT FROM AUTHOR]

The paper aims to develop a mathematical model for the investigation of degradation of a porous matrix of polylactic acid implanted in a bone tissue based on the study of kinetics of hydrolytic degradation of the matrix due to the action of a body fluid and diffusion of lactic acid released as a result of a chemical reaction. The numerical solution of nonstationary nonlinear equation of lactic acid diffusion through the host tissue obtained by the finite difference method allows one to establish a relationship between the lactic acid density in the bone tissue with time and the density during the implanted matrix degradation as well as the density profile of lactic acid in the bone tissue as a function of the kinetic reaction parameters for different porosities. The validation of the model is verified using the available experimental data. [ABSTRACT FROM AUTHOR]

Hip and knee replacement operations mostly utilize the cementing procedure, which determines the biocompatibility relevance of bone cement, a porous material, which is filled with the body fluid after surgery. The paper proposes a computer model of the bone cement mechanical behavior with explicit and implicit analyses of different-size pores, including isolated macropores. The multilevel simulation utilizes the movable cellular automaton method. The mechanical behavior of test samples, both dry and containing the body fluid, is studied under uniaxial compression and four-point bending. Nonlinear porosity dependences are detected for elastic and strength properties of bone cement during compression tests. [ABSTRACT FROM AUTHOR]

Scaffolds are microporous biocompatible structures that serve as material support for cells to proliferate, differentiate and form functional tissue. In particular, in the field of bone regeneration, insertion of scaffolds in a proper physiological environment is known to favour bone formation by releasing calcium ions, among others, triggering differentiation of mesenchymal cells into osteoblasts. Computational simulation of molecular distributions through scaffolds is a potential tool to study the scaffolds' performance or optimal designs, to analyse their impact on cell differentiation, and also to move towards reduction in animal experimentation. Unfortunately, the required numerical models are often highly complex and computationally too costly to develop parametric studies. In this context, we propose a computational parametric reduced-order model to obtain the distribution of calcium ions in the interstitial fluid flowing through scaffolds, depending on several physical parameters. We use the well-known Proper Orthogonal Decomposition (POD) with two different variations: local POD and POD with quadratic approximations. Computations are performed using two realistic geometries based on a foamed and a 3D-printed scaffolds. The location of regions with high concentration of calcium in the numerical simulations is in fair agreement with regions of bone formation shown in experimental observations reported in the literature. Besides, reduced-order solutions accurately approximate the reference finite element solutions, with a significant decrease in the number of degrees of freedom, thus avoiding computationally expensive simulations, especially when performing a parametric analysis. The proposed reduced-order model is a competitive tool to assist the design of scaffolds in osteoinduction research. [ABSTRACT FROM AUTHOR]

Introduction: Ashing is widely used to determine weight fraction of water-free bone that is mineral, but no standard procedure exists and the range of techniques used spans a range of temperatures and times over which the amount of weight loss is variable. We show that variability is largely due to progressive loss of CO2 from CO32− ions in the apatite crystal lattice, beginning at 600 ℃, typically used for ashing. We test the effect of varying temperature, time, and weight of sample and develop a reliable method, using small samples. Materials and methods: Replicate samples of bovine cortical bone were tested at 500 ℃, 600 ℃, and 700 ℃ for times ranging up to 24 h. We also tested samples of multiple humans at what we concluded to be the optimal conditions. Results: Varying conditions of ashing resulted in variations in apparent ash weight % by up to 7%. Samples between 5 and 20 mg heated to 600 ℃ for 1 h gave results agreeing with generally accepted values, but with much smaller variability. Ash wt% values for multiple human bone samples differed by up to 4.8%, but replicate data for individuals agree to ± 1 wt%. Discussion: In conclusion, a satisfactory method is given for ash weight determination using small samples, and yielding highly reproducible data. If accepted widely, ash weight values between laboratories could be used to study variations due to diet, age, drug treatment, and disease. [ABSTRACT FROM AUTHOR]

Bone is a hierarchical material formed by an organic extracellular matrix and mineral where each component and their physical relationship with each other contribute to fracture resistance. Bone quality can be affected by nutrition, and dietary supplements that are marketed to improve overall health may improve the fracture resistance of bone. To test this, 11 week old female C57BL/6 mice were fed either collagen, chondroitin sulfate, glucosamine sulfate, or fish oil 5 times a week for 8 weeks. Femurs, tibiae, and vertebrae were scanned with micro-computed tomography and then mechanically tested. Glucosamine and fish oil lowered elastic modulus, but did not alter the overall strength of the femur. There were no differences in bone mechanics of the tibiae or vertebrae. Overall, the data suggest that dietary supplements did little to improve bone quality in young, healthy mice. These supplements may be more effective in diseased or aged mice. [ABSTRACT FROM AUTHOR]

Bone is an extraordinary biological material that continuously adapts its hierarchical microstructure to respond to static and dynamic loads for offering optimal mechanical features, in terms of stiffness and toughness, across different scales, from the sub-microscopic constituents within osteons—where the cyclic activity of osteoblasts, osteoclasts, and osteocytes redesigns shape and percentage of mineral crystals and collagen fibers—up to the macroscopic level, with growth and remodeling processes that modify the architecture of both compact and porous bone districts. Despite the intrinsic complexity of the bone mechanobiology, involving coupling phenomena of micro-damage, nutrients supply driven by fluid flowing throughout hierarchical networks, and cells turnover, successful models and numerical algorithms have been presented in the literature to predict, at the macroscale, how bone remodels under mechanical stimuli, a fundamental issue in many medical applications such as optimization of femur prostheses and diagnosis of the risk fracture. Within this framework, one of the most classical strategies employed in the studies is the so-called Stanford's law, which allows uploading the effect of the time-dependent load-induced stress stimulus into a biomechanical model to guess the bone structure evolution. In the present work, we generalize this approach by introducing the bone poroelasticity, thus incorporating in the model the role of the fluid content that, by driving nutrients and contributing to the removal of wastes of bone tissue cells, synergistically interacts with the classical stress fields to change homeostasis states, local saturation conditions, and reorients the bone density rate, in this way affecting growth and remodeling. Through two paradigmatic example applications, i.e. a cylindrical slice with internal prescribed displacements idealizing a tract of femoral diaphysis pushed out by the pressure exerted by a femur prosthesis and a bone element in a form of a bent beam, it is highlighted that the present model is capable to catch more realistically both the transition between spongy and cortical regions and the expected non-symmetrical evolution of bone tissue density in the medium–long term, unpredictable with the standard approach. A real study case of a femur is also considered at the end in order to show the effectiveness of the proposed remodeling algorithm. [ABSTRACT FROM AUTHOR]

Thalassemia causes anemia, ineffective erythropoiesis, bone loss and iron accumulation in several tissues, e.g., liver, bone and heart, the last of which leads to lethal cardiomyopathy and arrhythmia. Although exercise reportedly improves bone density in thalassemic mice, exercise performance is compromised and might pose risk of cardiovascular accident in thalassemic patients. Therefore, we sought to explore whether mild-intensity physical activity (MPA) with 30–50% of maximal oxygen consumption was sufficient to benefit the heart and bone. Herein, male hemizygous β-globin knockout (BKO) mice and wild-type littermates were subjected to voluntary wheel running 1 h/day, 5 days/week for 3 months (MPA group) or kept sedentary (SDN; control). As determined by atomic absorption spectroscopy, BKO-MPA mice had less iron accumulation in heart and bone tissues compared with BKO-SDN mice. Meanwhile, the circulating level of fibroblast growth factor-23—a factor known to reduce serum iron and intestinal calcium absorption—was increased early in young BKO-MPA mice. Nevertheless, MPA did not affect duodenal calcium transport or body calcium retention. Although MPA restored the aberrant bone calcium-phosphorus ratio to normal range, it did not change vertebral calcium content or femoral mechanical properties. Microstructural porosity in tibia of BKO-MPA mice remained unaltered as determined by synchrotron radiation X-ray tomographic microscopy. In conclusion, MPA prevents cardiac and bone iron accumulation, which is beneficial to thalassemic patients with limited physical fitness or deteriorated cardiac performance. However, in contrast to moderate-intensity exercise, MPA does not improve bone mechanical properties or reduce bone porosity. [ABSTRACT FROM AUTHOR]

The Toca das Onças cave is one of the most important Quaternary mammal deposits of Brazil. Two different hypotheses have been proposed to explain the preservation mode of its skeletal remains: either the animals climbed down into the cave, or it could have functioned as a natural trap. Evaluation of pathological modifications on three articulated vertebrae of a single adult giant ground sloth Eremotherium laurillardi reveals a particular type of bone fracture caused by compressive force on the vertebral column, which split the vertebral bodies in the sagittal plane. This diagnosis suggests that the animal accidentally fell into the cave, in accordance with the second hypothesis proposed to the incorporation mode of skeletal remains into the cave. [ABSTRACT FROM AUTHOR]

Modeling of cancellous bone has important applications in the detection and treatment of fatigue fractures and diseases like osteoporosis. In this paper, we present a fully coupled multiscale approach considering mechanical, electric and magnetic effects by using the multiscale finite element method and a two-phase material model on the microscale. We show numerical results for both scales, including calculations for a femur bone, comparing a healthy bone to ones affected by different stages of osteoporosis. Here, the magnetic field strength resulting from a small mechanical impact decreases drastically for later stages of the disease, confirming experimental research. [ABSTRACT FROM AUTHOR]

Osteoporosis-related bone fragility fractures are a major public health concern. Given the potential for adverse side effects of pharmacological treatment, many have sought alternative treatments, including dietary changes. Based on recent evidence that polyphenol-rich foods, like blueberries, increase calcium absorption and bone mineral density (BMD), we hypothesized that blueberry polyphenols would improve bone biomechanical properties. To test this, 5-month-old ovariectomized Sprague-Dawley rats (n = 10/gp) were orally gavaged for 90 days with either a purified extract of blueberry polyphenols (0–1000 mg total polyphenols/kg bw/day) or lyophilized blueberries (50 mg total polyphenols/kg bw/day). Upon completion of the dosing regimen, right femur, right tibia, and L1–L4 vertebrae were harvested and assessed for bone mineral density (BMD), with femurs being further analyzed for biomechanical properties via three-point bending. There were no differences in BMD at any of the sites analyzed. For bone mechanical properties, the only statistically significant difference was the high dose group having greater ultimate stress than the medium dose, although in the absence of differences in other measures of bone mechanical properties, we concluded that this result, while statistically significant, had little biological significance. Our results indicate that blueberry polyphenols had little impact on BMD or bone mechanical properties in an animal model of estrogen deficiency-induced bone loss. [ABSTRACT FROM AUTHOR]

Detailed information on skeletal trauma analysis of burned bone is important to ascertain the manner and cause of death in forensic casework. This research used three different knife types, one with a non-serrated blade, one a fine-serrated blade, and one a coarse-serrated blade, to inflict trauma to manually macerated Sus scrofa ribs (n = 240), and these ribs were later exposed to heat. Qualitative and quantitative analyses were conducted using macroscopic and microscopic techniques to assess specific characteristics of the cut marks. Differences in cut mark dimension and morphology of the ribs were investigated. After heat exposure, the cut marks on the rib samples remained recognisable and did not alter considerably. A level of dimensional and morphological preservation was reliant on the cutting action and the features of the knife blade as well as surrounding bone injury. The cut marks inflicted by the non-serrated blade remained recognisable despite exposure to the burning process. However, the cut marks inflicted by the coarse-serrated blade were likely to change significantly when exposed to heat. This study leads to two important results: (1) identification of pre-existing cut marks prior to heat exposure is possible in reconstructed burned bone fragments, and (2) cut marks from different types of knife blades showed dissimilar responses to heat. The outcomes obtained in this study stressed the need to adopt great care with the effects of heat on skeletal trauma analysis. [ABSTRACT FROM AUTHOR]

We have recently revealed significant differences in microarchitectural properties (i.e. global and local morphometries) and mechanical properties between rheumatoid arthritis (RA), osteoarthritis (OA) and osteoporosis (OP) in cancellous bones. This study compared these properties with those of ageing controls by matching bone volume fraction (BV/TV), the most important determinant for bones' mechanical properties, to investigate whether these bones have similar properties and degenerative potentials. RA, OA and OP femoral heads were harvested from patients undergoing total hip replacement surgery. The selected patients were matched by similar cancellous bone BV/TV, with seven patients in each group. Four samples were prepared from each femoral head and scanned with micro-CT to quantify microarchitectural properties and compression tested to determine mechanical properties. In terms of global morphometry, no significant differences were observed between these diseased bones. In terms of local morphometry, the number of plates in the RA group was significantly greater than that of the OP and control groups. Plate volume density in the RA group was significantly greater than in the control group. Interestingly, the ultimate stresses in the three diseased groups were 77% to 195% lower than in the control group (p < 0.001). Degenerations of global morphometry of cancellous bones in these diseased femoral heads are similar but more severe than in ageing controls matched by BV/TV, as evidenced by pronounced reduction in bone strength. This phenomenon suggests that some local morphometric parameters, along with other factors, such as abnormal collagen, mineralisation, erosion and microdamage, may contribute to further compromising mechanical properties. [ABSTRACT FROM AUTHOR]

Femur bone fracture is mainly caused by sports injuries or accidents and has become serious attention in orthopedic trauma. The unique cortical bone microstructures and features contribute to complex fracture behavior. This paper presents the investigation of Type 2 and Type 3 arch-shaped microcrack penetration based on von Mises stress and stress intensity factor (SIF) parameters around the microcrack tips penetration in Haversian system cortical bones. The fracture model was constructed based on bone continuum mechanics theory named Kachanov theory of elastic interaction. It aims to determine the level of stress amplification and stress shielding for the transition of Type 2 to Type 3 for heterogeneous cortical bone fracture model. A total of eight microcrack extension points (CP1–8) were constructed based on 1-mm2 Haversian system model, subjected to the force of 10 N in Mode I and Mode II loading. Finite element (FE) analysis was then performed to evaluate the von Mises stress around the crack end tips and SIF under the assumption of bone damage, D < 1. The study found that the greatest von Mises stress value was observed at the CP4 (175.766 MPa) and CP8 (213.264 MPa) for Mode I loading and CP4 (106.037 MPa) for Mode II loading. In terms of fracture parameter, the critical SIF magnitude was peaked at CP4 (1272.8 MPa*m1/2) and CP8 (1369.0 MPa*m1/2) for Mode I loading and CP5 (402.29 MPa*m1/2) for Mode II loading. The results show that the transition of Type 2 (straight crack) to Type 3 (arch crack) microcrack penetration in Haversian system experienced the multilevel of stress amplification (CP1–CP4, CP6–8) and stress shielding (CP4–CP6) to represent the bone micro-damage level. [ABSTRACT FROM AUTHOR]

Although current commercial acrylic bone cements have been used successfully in total joint replacement surgery for over five decades, some further improvement are being investigated to cope with cement failure, one approach is surface modification of BaSO4 particles to improve its interfacial adhesion with the polymeric matrix in acrylic bone cements formulations. In this article, BaSO4 particles were modified by different surface treatments. The first of them involved the use of 3-(trimethoxysilyl)propyl methacrylate as a coupling agent; in the second, the radiopaque particles were exposed to oxygen plasma at power levels of 15 and 70 W, followed by MPS coupling agent and the last one consisted in exposing the radiopaque particles to methyl methacrylate (MMA) plasma. Mechanical properties of the bone cements prepared with modified BaSO4 particles were improved due to its higher dispersion degree in polymeric matrix. [ABSTRACT FROM AUTHOR]

The piezoelectric response of bone at the submicron scale is analyzed under mechanical loadings using the finite element (FE) method. A new algorithm is presented to virtually reconstruct realistic bone nanostructures, consisting of collagen fibrils embedded in a hydroxyapatite mineral network. This algorithm takes into account potential misalignments between fibrils, as well the porous structure of the mineral phase. A parallel non-iterative mesh generation algorithm is utilized to create high-fidelity FE models for several representative volume elements (RVEs) of the bone with various fibrils volume fractions and misalignments. The piezoelectric response of each RVE is simulated under three types of loading: the longitudinal compression, lateral compression, and shear. The resulting homogenized stress and electric field in RVEs with aligned fibrils showed a linear variation with the fibrils volume fraction under all loading conditions. For RVEs with misaligned fibrils, although more oscillations were observed in homogenized results, their difference with the results of RVEs with aligned fibrils subject to lateral compression and shear loadings were negligible. However, under longitudinal compression, the electric field associated with RVEs with misaligned fibrils was notably higher than that of RVEs with aligned fibrils for the same volume fraction. [ABSTRACT FROM AUTHOR]

This paper deals with the numerical prediction of the elastic modulus of trabecular bone in the femoral head (FH) and the intertrochanteric (IT) region via site-specific bone quality assessment using solitary waves in a one-dimensional granular chain. For accurate evaluation of bone quality, high-resolution finite element models of bone microstructures in both FH and IT are generated using a topology optimization-based bone microstructure reconstruction scheme. A hybrid discrete element/finite element (DE/FE) model is then developed to study the interaction of highly nonlinear solitary waves in a granular chain with the generated bone microstructures. For more robust and reliable prediction of the bone's mechanical properties, a face sheet is placed at the interface between the last chain particle and the bone microstructure, allowing more bone volume to be engaged in the dynamic deformation during interaction with the solitary wave. The hybrid DE/FE model was used to predict the elastic modulus of the IT and FH by analysing the characteristic features of the two primary reflected solitary waves. It was found that the solitary wave interaction is highly sensitive to the elastic modulus of the bone microstructure and can be used to identify differences in bone density. Moreover, it was found that the use of a relatively stiff face sheet significantly reduces the sensitivity of the wave interaction to local stiffness variations across the test surface of the bone, thereby enhancing the robustness and reliability of the proposed method. We also studied the effect of the face sheet thickness on the characteristics of the reflected solitary waves and found that the optimal thickness that minimizes the error in the modulus predictions is 4 mm for the FH and 2 mm for the IT, if the primary reflected solitary wave is considered in the evaluation process. We envisage that the proposed diagnostic scheme, in conjunction with 3D-printed high-resolution bone models of an actual patient, could provide a viable solution to current limitations in site-specific bone quality assessment. [ABSTRACT FROM AUTHOR]

This work proposes a novel tissue-scale mechanobiological model of bone remodeling to study bone's adaptation to distinct loading conditions. The devised algorithm describes the mechanosensitivity of bone and its impact on bone cells' functioning through distinct signaling factors. In this study, remodeling is mechanically ruled by variations of the strain energy density (SED) of bone, which is determined by performing a linear elastostatic analysis combined with the finite element method. Depending on the SED levels and on a set of biological signaling factors (g parameters), osteoclasts and osteoblasts can be mechanically triggered. To reproduce this phenomenon, this work proposes a new set of g parameters. The combined response of osteoclasts and osteoblasts will then affect bone's apparent density, which is correlated with other mechanical properties of bone, through a phenomenological law. Thus, this novel model proposes a constant interplay between the mechanical and biological components of the process. The spatiotemporal simulation used to validate this new approach is a benchmark example composed by two distinct phases: (1) pre-orientation and (2) load adaptation. On both of them, bone is able to adapt its morphology according to the loading condition, achieving the required trabecular distribution to withstand the applied loads. Moreover, the equilibrium morphology reflects the orientation of the load. These preliminary results support the new approach proposed in this study. [ABSTRACT FROM AUTHOR]

Current treatment options for osteoporosis primarily involve pharmacotherapies, but they are often accompanied by undesirable side effects. Utilization of mechanical stress which can noninvasively induce bone formation has been suggested as an alternative to conventional treatments. Here, we examined the efficacy of mechanical stress induced by electrical stimulation, radial extracorporeal shock waves, and ultrasound for estrogen-deficient osteoporosis. Female Wistar rats were divided into following five groups: sham-operated group, untreated after ovariectomy, and treated with electrical stimulation, radial extracorporeal shock wave, or ultrasound starting at 8 weeks after ovariectomy for 4 weeks. Trabecular bone architecture of the femur was assessed by micro-CT and its biomechanical properties were obtained by mechanical testing. The femurs were further evaluated by histochemical, immunohistochemical, and real-time PCR analyses. Radial extracorporeal shock wave and ultrasound treatment improved trabecular bone microarchitecture and bone strength in osteoporotic rats, but not electrical stimulation. The shock wave decreased osteoclast activity and RANKL expression. The exposure of ultrasound increased osteoblast activity and β-catenin-positive cells, and they decreased sclerostin-positive osteocytes. These findings suggest that mechanical stress induced by radial extracorporeal shock wave and ultrasound can improve estrogen-deficient bone loss and bone fragility through promoted bone formation or attenuated bone resorption. [ABSTRACT FROM AUTHOR]

An oblique double-cut rotation osteotomy (ODCRO) enables correcting a complex bone deformation by aligning, in 3D, the distal, middle and proximal bone segments with a target bone, without intersegmental gaps. We propose virtual preoperative planning of an ODCRO. To minimize a residual translation error, we use an optimization algorithm and optimize towards bone length, alignment in the transverse direction, or a balanced reconstruction. We compare the residual alignment error with an oblique single-cut rotation osteotomy using 15 complex bone deformations. The single-cut approach was not feasible in 5 cases, whereas the ODCRO procedure was feasible in all cases. The residual alignment error was smaller for the ODCRO than for the single-cut approach except for one case. In a subset for length reconstruction, the length error of 7.3–21.3 mm was restored to 0.0 mm in 4 of 5 cases, although at the cost of an increased transverse translation. The proposed method renders planning an ODCRO feasible and helps restoring bone alignment and lengthening better than an oblique single-cut rotation osteotomy. Awareness of the challenges and possibilities in preoperative planning of an ODCRO will be of value for future alignment surgery and for patients. [ABSTRACT FROM AUTHOR]

Bone mineral carbonate content assessed by vibrational spectroscopy relates to fracture incidence, and mineral maturity/ crystallinity (MMC) relates to tissue age. As FT-IR and Raman spectroscopy become more widely used to characterize the chemical composition of bone in pre-clinical and translational studies, their bone mineral outcomes require improved validation to inform interpretation of spectroscopic data. In this study, our objectives were (1) to relate Raman and FT-IR carbonate:phosphate ratios calculated through direct integration of peaks to gold-standard analytical measures of carbonate content and underlying subband ratios; (2) to relate Raman and FT-IR MMC measures to gold-standard analytical measures of crystal size in chemical standards and native bone powders. Raman and FT-IR direct integration carbonate:phosphate ratios increased with carbonate content (Raman: p < 0.01, R2 = 0.87; FT-IR: p < 0.01, R2 = 0.96) and Raman was more sensitive to carbonate content than the FT-IR (Raman slope + 95% vs FT-IR slope, p < 0.01). MMC increased with crystal size for both Raman and FT-IR (Raman: p < 0.01, R2 = 0.76; FT-IR p < 0.01, R2 = 0.73) and FT-IR was more sensitive to crystal size than Raman (c-axis length: slope FT-IR MMC + 111% vs Raman MMC, p < 0.01). Additionally, FT-IR but not Raman spectroscopy detected differences in the relationship between MMC and crystal size of carbonated hydroxyapatite (CHA) vs poorly crystalline hydroxyapatites (HA) (slope CHA + 87% vs HA, p < 0.01). Combined, these results contribute to the ability of future studies to elucidate the relationships between carbonate content and fracture and provide insight to the strengths and limitations of FT-IR and Raman spectroscopy of native bone mineral. [ABSTRACT FROM AUTHOR]