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BACKGROUND: Postmenopausal osteoporosis significantly increases the risk of fracture, which seriously affects the quality of life of patients. Exercise therapy is an important non-drug means and prevention and treatment strategy for patients with osteoporosis, in which strength training is the best mode, but its specific biological mechanism has not been determined. OBJECTIVE: To investigate the effects of strength training on bone morphology, materials and biomechanics in ovariectomized rats and to explore the mechanism of extracellular matrix remodeling. METHODS: Forty-eight female Sprague-Dawley rats were divided into sham operation group, sham operation exercise group, ovariectomized group and ovariectomized exercise group according to the random number table method. The menopausal animal model was established by bilateral ovariectomy in the ovariectomized group and ovariectomized exercise group, while sham operation was performed in the sham operation group and sham operation exercise group. Four weeks after operation, the sham operation exercise group and the ovariectomized exercise group underwent 12-week tail weight-bearing ladder training, and the sham operation group and the ovariectomized group were raised quietly in the cage. The bilateral femur and tibia were separated after training. The right tibia was used for dual-energy X-ray densitometry and biomechanical, biophysical and biochemical analyses, the left tibia was detected using micro-computed tomography for bone microstructural examination, the right femur was subjected to hematoxylin-eosin staining for histological observation, and the left femur was used for western blot and gelatin zymography detection of protein expression and enzyme activity of extracellular matrix metabolismrelated factors, respectively. RESULTS AND CONCLUSION: Compared with the sham operation group, the maximal load and stiffness decreased (P < 0.05), bone density, bone mineral density, bone inorganic matter content, bone calcium content decreased (P < 0.05), bone water content increased (P < 0.05), trabecular bone volume fraction, trabecular connectivity density, and trabecular number decreased (P < 0.05), trabecular separation, structural model index increased (P < 0.05), bone adipocyte number and cross-sectional area increased (P < 0.05), matrix metalloproteinase-2 activity decreased (P < 0.05), and protein expression of tissue inhibitor of metalloproteinase-1 and osteoprotegerin increased (P < 0.05) in the ovariectomized group. Compared with the ovariectomized group, the maximal load, stiffness, fracture load and resilience increased (P < 0.05), bone mineral density, bone mineral content, bone mineral density, bone inorganic matter content, and bone calcium content increased (P < 0.05), bone water content decreased (P < 0.05), trabecular separation and bone marrow area decreased (P < 0.05), trabecular bone thickness, cortical bone volume fraction, cortical bone area fraction, cortical bone thickness, and cortical bone porosity increased (P < 0.05), bone adipocyte number and cross-sectional area reduced (P < 0.05), matrix metalloproteinase-2 activity increased (P < 0.05), and protein expression of tissue inhibitor of metalloproteinase-1, Runt-related transcription factor 2 and osteoprotegerin decreased (P < 0.05) in the ovariectomized exercise group. To conclude, strength training can protect against bone injury caused by estrogen deficiency, which is characterized by improvement of bone biomechanical properties, bone tissue composition and bone microstructure, and its mechanism is related to the regulation of extracellular matrix remodeling. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exercise is an effective method for preventing and treating osteoporosis, but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE: To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats, and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS: A rat model of postmenopausal osteoporosis was established, and a 24-week moderate-intensity exercise was used for intervention. After the experiment, serum estradiol levels were measured by ELISA, and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT. The biomechanical indicators of the tibia were tested by a three-point bending test. Autophagosomes were observed by transmission electron microscopy. The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION: The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group (P < 0.01). The body mass of rats in each group increased, and the order was the ovariectomized group > the ovariectomized+exercise group > the sham-operation group > the sham-operation+exercise group. The bone mineral density and bone mass of rats in all groups significantly increased (P < 0.01), but the increase in the ovariectomized group was significantly lower than that of the other groups, and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group. Compared with the sham-operation group, the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased (P < 0.01), while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased (P < 0.01). Compared with the ovariectomized+exercise group, the ovariectomized group showed significantly lower bone volume fraction, number of trabeculae, and bone mineral density of cancellous bone (P < 0.05), extremely significantly lower trabecular thickness (P < 0.01), and significantly higher mean trabecular pattern factor, trabecular separation, and structural model index (P < 0.01). Compared with the ovariectomized group, the LC3-II/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group (P < 0.05). Compared with the sham-operation and ovariectomized groups, the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups, respectively. To conclude, moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels. [ABSTRACT FROM AUTHOR]

Polyetheretherketone (PEEK), with good biocompatibility and similar mechanical properties to natural bone, is extensively employed in the manufacture of prostheses. However, the precision and mechanical properties of current implants are major challenges for clinical applications. In this study, the effect of pore size, raster angle and printing temperature were investigated on length, width, thickness, material consumption, compressive strength and Young's modulus. Taguchi design of experiment method was used to reduce the number of experiments and optimize the printing process parameters. Finally, predictive analysis was exploited to give the optimal set of process parameters. Experimental results indicated that the approach applied in this work provided more accurate predictions and control of the response variables. The maximum compressive strength and compressive modulus of PEEK scaffolds reached 43.4 MPa and 253.3 MPa, respectively. Therefore, the methodology of present work has the potential to meet the demand of design precision and manufacture of customized bone substitutes. [ABSTRACT FROM AUTHOR]

[Display omitted] Mechanical loading is required for bone homeostasis, but the underlying mechanism is still unclear. Our previous studies revealed that the mechanical protein polycystin-1 (PC1, encoded by Pkd1) is critical for bone formation. However, the role of PC1 in bone resorption is unknown. Here, we found that PC1 directly regulates osteoclastogenesis and bone resorption. The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts, decreased bone resorption, and increased bone mass. A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease, which is mainly caused by loss-of-function mutation of the PKD1 gene, is associated with a lower risk of hip fracture than those with other chronic kidney diseases. Moreover, mice with osteoclast-specific knockout of Pkd1 showed complete resistance to unloading-induced bone loss. A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass. Pharmacological regulation of the PC1-TAZ axis alleviated unloading- and estrogen deficiency- induced bone loss. Thus, the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis. [ABSTRACT FROM AUTHOR]

The article discusses the development and growth of bones in the human body. It explains that bones are made up of a specialized form of connective tissue with collagen fibers and minerals, which give them strength and rigidity. Bones serve as a framework for the body, support organs, produce blood cells, store calcium and phosphorus, and have recently been recognized as an endocrine tissue. The article also explores the two main mechanisms of bone formation: intramembranous ossification and endochondral ossification. It highlights the simultaneous occurrence of these processes during bone healing and the potential for chondrocytes to transdifferentiate into osteoblasts. The article concludes by emphasizing the complexity of bone biology and the need for further research to improve our understanding and develop new therapeutic methods. [Extracted from the article]

Osteoblasts are mechanosensitive cells. Tensile stress with different conditions, including loading time, frequency, magnitude, etc. would cause varied responses in osteoblasts. However, it was not clarified that the effect of the loading types on the osteoblasts. In this study, we focused on the effect of varied tensile stress types on osteoblasts, including isotropic stretch, biaxial stretch, and uniaxial stretch with the negative ratio of transverse strain to axial strain (NR) −1, 0, and 0.2 respectively. Cell proliferation was determined to be most efficient when stimulated by 6% strain at a frequency of 1 Hz and a negative value of 0 for 1 h/day. The varied strain resulted in a thickening of the F-actin cytoskeleton and a thinning of the nucleus. Nuclear flattening caused Yes-associated protein (YAP) to be transported to the nucleus. It was suggested that the influence of loading types on the mechanobiology responses must be noticed. The mechanism of cell mechanical sensitivity under varied loading types was explored, which would provide good suggestions for designing microstructures to control deformation patterns in bone tissue engineering. [ABSTRACT FROM AUTHOR]

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]

Combined treatment with PTH(1‐34) and mechanical loading confers increased structural benefits to bone than monotherapies. However, it remains unclear how this longitudinal adaptation affects the bone mechanics. This study quantified the individual and combined longitudinal effects of PTH(1‐34) and mechanical loading on the bone stiffness and strength evaluated in vivo with validated micro‐finite element (microFE) models. C57BL/6 mice were ovariectomised at 14‐week‐old and treated either with injections of PTH(1‐34), compressive tibia loading or both interventions concurrently. Right tibiae were in vivo microCT‐scanned every 2 weeks from 14 until 24‐week‐old. MicroCT images were rigidly registered to reference tibia and the cortical organ level (whole bone) and tissue level (midshaft) morphometric properties and bone mineral content were quantified. MicroCT images were converted into voxel‐based homogeneous, linear elastic microFE models to estimate the bone stiffness and strength. This approach allowed us for the first time to quantify the longitudinal changes in mechanical properties induced by combined treatments in a model of accelerated bone resorption. Both changes of stiffness and strength were higher with co‐treatment than with individual therapies, consistent with increased benefits with the tibia bone mineral content and cortical area, properties strongly associated with the tibia mechanics. The longitudinal data shows that the two bone anabolics, both individually and combined, had persistent benefit on estimated mechanical properties, and that benefits (increased stiffness and strength) remained after treatment was withdrawn. [ABSTRACT FROM AUTHOR]

Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and/or long‐term safety concerns. Proteoglycan‐4 (PRG4, also known as lubricin) is a mucin‐like glycoprotein best known for its boundary lubricating function of articular cartilage. In more recent years, it has been shown that PRG4 has anti‐inflammatory properties, contributes to the maintenance of subchondral bone integrity, and patients with PRG4 mutations are osteopenic. However, it remains unknown how PRG4 impacts mechanical and material properties of bone. Therefore, our objective was to perform a phenotyping study of bone in a Prg4 gene trap (GT) mouse (PRG4 deficient). We found that femurs of Prg4 GT mice have altered mechanical, structural, and material properties relative to wildtype littermates. Additionally, Prg4 GT mice have a greater number of calvarial osteoclasts than wildtype mice, but do not have a notable inflammatory serum profile. Finally, Prg4 GT mice do not have an altered rate of bone formation, and exogenous recombinant human PRG4 (rhPRG4) administration inhibited osteoclastogenesis in vitro, suggesting that the skeletal phenotype may be due to changes in bone resorption. Overall, this work demonstrates that PRG4 deficiency affects several integral properties of bone structure, mechanics, and skeletal cell activity, and provides the foundation and insight toward future work evaluating PRG4 as a potential therapeutic target in treating bone loss. [ABSTRACT FROM AUTHOR]

Both cell migration and osteogenic differentiation are critical for successful bone regeneration. Therefore, understanding the mechanobiological aspects that govern these two processes is essential in designing effective scaffolds that promote faster bone regeneration. Studying these two factors at different locations is necessary to manage bone regeneration in various sections of a scaffold. Hence, a multiscale computational model was used to observe the mechanical responses of osteoblasts placed in different positions of the trabecular bone and gyroid scaffold. Fluid shear stresses in scaffolds at cell seeded locations (representing osteogenic differentiation) and strain energy densities in cells at cell substrate interface (representing cell migration) were observed as mechanical response parameters in this study. Comparison of these responses, as two critical factors for bone regeneration, between the trabecular bone and gyroid scaffold at different locations, is the overall goal of the study. This study reveals that the gyroid scaffold exhibits higher osteogenic differentiation and cell migration potential compared to the trabecular bone. However, the responses in the gyroid only mimic the trabecular bone in two out of nine positions. These findings can guide us in predicting the ideal cell seeded sites within a scaffold for better bone regeneration and in replicating a replaced bone condition by altering the physical parameters of a scaffold. [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]

Background: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. Methods: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). Results: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = − 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = − 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased β-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). Conclusions: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: In recent years, numerous studies have shown that long non-coding RNAs (lncRNAs) have an important role in the pathogenesis of periodontitis, including the immune response process and the biological activity and function of cells (periodontal stem cells and osteoblasts). Researchers attempt to regulate periodontal inflammation and periodontal regeneration by regulating lncRNA expression levels. OBJECTIVE: To review the progress of research on lncRNAs in periodontitis, thereby advancing the research of lncRNAs in periodontitis. METHODS: The first author searched PubMed, China National Knowledge Infrastructure (CNKI), Web of Science database, and WanFang Database for relevant literature published up to March 2023. “Long non-coding RNA, lncRNA, periodontitis, periodontium, immunity, inflammation, periodontal ligament stem cells, osteoclasts, osteogenic differentiation, bone resorption, bone formation, recurrence, hypoxia, oxidative stress, static mechanical strain”were used as the Chinese search terms. “lncRNA, periodontitis, periodontal, immunity, inflammation, periodontal membrane stem cells, osteoclasts, osteogenic differentiation, bone resorption, bone formation, recurrence, hypoxia, oxidative stress, static mechanical strain” were used as the English search terms. The title and abstract of each paper were read for initial screening, and 87 papers were finally selected for inductive analysis. RESULTS AND CONCLUSION: Periodontal pathogens stimulate the body, leading to immune imbalance that triggers inflammatory response and destroy periodontal tissue, and lncRNAs are involved in its regulatory mechanism. LncRNAs are involved in the pro-inflammatory regulation of periodontal ligament cells in an inflammatory environment, and their effects on osteoclast differentiation are regulated through ceRNA mechanism, which provides new clues for exploring the pathogenesis of periodontitis. For B cells and macrophages, lncRNAs can regulate the infiltration, cell activity and function of their subsets in periodontitis. LncRNAs participate in the immune response related to periodontitis mainly through two pattern recognition receptors, Toll-like receptors and NOD-like receptors, and nuclear factor-κB signaling pathway. To investigate whether lncRNAs can be used as a biomarker of periodontitis has great value in the diagnosis and prognosis of periodontitis. Animal experiments have demonstrated that the role of lncRNAs in periodontitis can be reversed by modulating the expression level of lncRNAs and thus lncRNAs act as an anti-inflammatory agent, which is of great value for the study of immunotherapy in periodontitis. The regulation of lncRNAs on periodontal ligament stem cells is mainly realized through endogenous competition mechanism and various signaling pathways, and its effects are influenced by various factors, such as inflammatory environment, mechanical strain, hypoxia and oxidative stress. Research on related mechanisms through these related factors provides new ideas for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Background: Microgravity, a condition experienced in a spatial environment, poses unique challenges to the skeletal system, particularly in juvenile organisms. This study aimed to investigate alterations in bone biomechanics of juvenile mice due to unloading – that simulates microgravity in the laboratory—and the effects of a bone-loading intervention. We compared bone compositional and mechanical properties between 21-six-week-old C57Bl/6 from a control group (wild type) and a group that underwent a tail-suspension unloading protocol to mimic microgravity (MG). The second group (MG) experienced additional in vivo loading protocol (MG + LDG) on the right hind leg, where dynamic compressive loading was applied to the right knee using a custom-built loading device. Results: Our results show that after two weeks, we successfully induced bone alterations by (i) decreasing the energy dissipated before fracture and (ii) decreasing the yield and maximum stress. In addition, we showed that Mineral to matrix component [ν1PO4/Amide I], Carbonate to Amide [CO3/Amide I], and Crystallinity [1/FWHM(ν1PO4)] are strongly linked in physiological bone but not in microgravity even after loading intervention. While Crystallinity is very sensitive to bone deformation (strain) alterations coming from simulated microgravity, we show that Carbonate to Amide [CO3/Amide I] – a common marker of turnover rate/remodeling activity—is a specific predictor of bone deformation for bone after simulated microgravity. Our results also invalidate the current parameters of the loading intervention to prevent bone alterations entirely in juvenile mice. Conclusions: Our study successfully induced bone alterations in juvenile mice by using an unloading protocol to simulate microgravity, and we provided a new Raman Spectroscopy (RS) dataset of juvenile mice that contributes to the prediction of cortical bone mechanical properties, where the degree of interrelationship for RS data for physiological bone is improved compared to the most recent evidence. [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]

The elemental composition of chemical elements can vary between healthy and diseased tissues, providing essential insights into metabolic processes in physiological and diseased states. This study aimed to evaluate the calcium (Ca) and phosphorus (P) levels in the bones of rats with/without streptozotocin-induced diabetes and/or exposure to infrasound. X-ray fluorescence spectroscopy was used to determine the concentrations of Ca and P in Wistar rat tibiae samples. The results showed a significant decrease in bone P concentration in streptozotocin-induced diabetic rats compared to untreated animals. Similarly, the Ca/P ratio was higher in the streptozotocin-induced diabetic group. No significant differences were observed in bone Ca concentration between the studied groups or between animals exposed and not exposed to infrasound. Moreover, streptozotocin-induced diabetic rats had lower bone P concentration but unaltered bone Ca concentration compared to untreated rats. Infrasound exposure did not impact bone Ca or P levels. The reduced bone P concentration may be associated with an increased risk of bone fractures in diabetes. [ABSTRACT FROM AUTHOR]

This study evaluates the potential for osseointegration and remodeling of customized dental implants made from Titanium-Hydroxyapatite Functionally Graded Material (Ti-HAP FGM) with optimized geometry, using the finite element method (FEM). The study utilized CT scan images to model and assemble various geometrical designs of dental implants in a mandibular slice. The mechanical properties of Ti-HAP FGMs were computed by varying volume fractions (VF) of hydroxyapatite (0–20%), and a bone remodeling algorithm was used to evaluate the biomechanical characteristics of the ultimate bone configuration in the peri-implant tissue. The findings of the FEA reveal that osseointegration improves with changes in the density and mechanical properties of the bone surrounding Ti-HAP implants, which are influenced by the varying VF of hydroxyapatite in the FGM. Increasing the hydroxyapatite fraction improves osseointegration, and appropriate length and diameter selection of Ti-HAP dental implants contribute to their stability and longevity. [Display omitted] [ABSTRACT FROM AUTHOR]

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL–TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL–TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion. [ABSTRACT FROM AUTHOR]

Background: The mechanical characteristics of bone are crucial for comprehending its functionality and response to different load conditions, which are essential for advancing medical treatments, implants, and prosthetics. By employing mathematical modeling to analyze the mechanical properties of bone, we can assess stress and deformation under both normal and abnormal conditions. This analysis offers valuable perspectives on potential fracture risks, the effects of diseases, and the effectiveness of various treatments. Therefore, researchers are attempting to find an adequate mathematical description of the mechanical properties of bone. Methods: Experimental stress–stretch external loading curves were obtained through investigations of canine vertebrae. The obtained experimental curves were fitted using the SciPy Python library with a slightly modified logistic function (logistic function plus additional const). Results: The resulting coefficient of determination  R 2  (R squared) for most curves was near 0.999, indicating that an appropriate fitting function was selected for the description of the experimental stress–stretch curves. Conclusions: The stress–stretch behavior of canine vertebrae can be described using a logistic function modified by adding additional parameters for the most accurate fitting results. [ABSTRACT FROM AUTHOR]

• Syndecan 4 null mice show vertebral osteopenia, reduced bone stiffness, and functionally altered bone biomechanics. • Osteopenic phenotype in Sdc4 null mice is driven by elevated osteoclast numbers. • Syndecan 4 fine-tunes collagen maturity and ECM composition in the intervertebral disc during early adult life. • Transcriptomic analysis shows dysregulation in heparan sulfate biosynthesis, UPR, and degradation along with decreased mitochondria metabolism. Syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan, is known to regulate matrix catabolism by nucleus pulposus cells in an inflammatory milieu. However, the role of SDC4 in the aging spine has never been explored. Here we analyzed the spinal phenotype of Sdc4 global knockout (KO) mice as a function of age. Micro-computed tomography showed that Sdc4 deletion severely reduced vertebral trabecular and cortical bone mass, and biomechanical properties of vertebrae were significantly altered in Sdc4 KO mice. These changes in vertebral bone were likely due to elevated osteoclastic activity. The histological assessment showed subtle phenotypic changes in the intervertebral disc. Imaging-Fourier transform-infrared analyses showed a reduced relative ratio of mature collagen crosslinks in young adult nucleus pulposus (NP) and annulus fibrosus (AF) of KO compared to wildtype discs. Additionally, relative chondroitin sulfate levels increased in the NP compartment of the KO mice. Transcriptomic analysis of NP tissue using CompBio, an AI-based tool showed biological themes associated with prominent dysregulation of heparan sulfate GAG degradation, mitochondria metabolism, autophagy, endoplasmic reticulum (ER)-associated misfolded protein processes and ER to Golgi protein processing. Overall, this study highlights the important role of SDC4 in fine-tuning vertebral bone homeostasis and extracellular matrix homeostasis in the mouse intervertebral disc. [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]

The influence of cobalt ion dopant on the in vitro biological properties of biphasic calcium phosphate (BCP) was investigated with an aim to develop an effective scaffold for bone tissue engineering applications. Cost-efficient wet chemical method was used to prepare in-situ cobalt doped BCP and XRD, FTIR, Raman spectroscopy, FESEM analyses were performed for detailed physico-chemical characterizations. It has been observed that pure BCP is comprised of 98 vol% of β-TCP and 2 vol% of β-CPP, whereas incorporation of cobalt leads to 58.8 vol% of β-TCP and 41.4 vol% of β-CPP. Moreover, Co-doped BCP exhibited relatively larger particle size when compared to pure BCP as observed in FESEM analysis. Furthermore, cobalt doped BCP showed enhanced antibacterial activity and the zone of inhibition was prominent compared to pure BCP. The release of cobalt ions from doped BCP was analyzed by Inductively Coupled Plasma (ICP) mass spectrometry at different time points (up to 28 days) and sustained release of cobalt ions warrants its benefits in native tissue regeneration. Both pure and Co-doped BCP showed excellent hemocompatibility as the percentage of hemolysis was below 2 %. Cell viability was found to be marginally higher with incorporation of trace amount of cobalt in BCP. Notably, in vitro angiogenic activity assessment results confirmed that VEGF-A and HIF-1α gene expression was significantly enhanced in case of doped BCP compared to pure BCP, signifying that the cobalt doping considerably improved the expression of angiogenic factors. Over the study, results demonstrated that incorporation of cobalt as dopants can effectively improve the in vitro biological properties of biphasic calcium phosphate based bioceramics and might be considered as a new generation bone grafts in bone regeneration applications. [ABSTRACT FROM AUTHOR]

Visualization and analysis of microstructure of materials or tissue play a pivotal role in industrial manufacturing and pathological diagnosis. Microwave-induced thermoacoustic microscopy (TAM) enables imaging at the microscopic level. TAM, however, is currently qualitative and cannot quantitatively measure intrinsic electromagnetic parameters of materials/tissue, such as conductivity. Here, we propose a quantitative microwave-induced thermoacoustic microscopy (qTAM) approach capable of quantitatively recovering conductivity using a finite element-based iterative inversion strategy coupled with thermoacoustic measurements. We validate the qTAM approach using tissue-mimicking phantoms, and demonstrate its applications to imaging flexible circuits, ex vivo rabbit bone, and rat brain tissues. The results obtained suggest that qTAM may have the potential to become a quantitative tool for microscopic imaging of materials and tissues. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hydroxyapatite is the main inorganic component of bone tissue. The polymer has the structure and function of a biomimetic extracellular matrix. The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE: To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS: The articles collected in PubMed, Web of Science, CNKI and WanFang databases were searched from January 2010 to April 2023. The Chinese and English search terms were “hydroxyapatite, polymer, composites, degradability, bone defect, bone repair”. Finally, 75 articles were included for review. RESULTS AND CONCLUSION: Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers (collagen, chitosan, alginate, serine protein, cellulose, hyaluronic acid,and polyhydroxybutyrate) and synthetic polymers [polylactic acid, polylactic acid-hydroxyacetic acid copolymer, poly(has-lactide), poly(amino acid) and poly(vinyl alcohol)]. The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite. Hydroxyapatite composite with polymers can be made into porous scaffolds, hydrogels, and coatings for bone repair. Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function. Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins, repair materials with mechanical properties matching bone tissue, degradation processes synchronized with bone repair, and efficient osteogenesis and vascularization need to be further investigated. [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]

Simple Summary: Bone tissue engineering is one of the most promising approaches for the restoration of large bone defects. Nevertheless, to date, several disadvantages limit its use due to an inability to completely fulfill all the clinical needs. In this context, in recent years, the application of nanotechnology to improve the mechanical, chemical–physical, and biological properties of biomaterials for bone tissue engineering has received great interest from researchers. Nanomaterials, including nanoparticles, are the key elements of such nanotechnologies due to their high penetrating ability and surface area, mechanical strength enhancement, improved cell adhesion, differentiation, and growth, enhanced antibacterial properties, and biocompatibility. In this review, we report on the latest in vitro and in vivo studies on the combination of nanotechnology and bone tissue engineering as promising approach for the regeneration of large bone defects. Large bone defects are the leading contributor to disability worldwide, affecting approximately 1.71 billion people. Conventional bone graft treatments show several disadvantages that negatively impact their therapeutic outcomes and limit their clinical practice. Therefore, much effort has been made to devise new and more effective approaches. In this context, bone tissue engineering (BTE), involving the use of biomaterials which are able to mimic the natural architecture of bone, has emerged as a key strategy for the regeneration of large defects. However, although different types of biomaterials for bone regeneration have been developed and investigated, to date, none of them has been able to completely fulfill the requirements of an ideal implantable material. In this context, in recent years, the field of nanotechnology and the application of nanomaterials to regenerative medicine have gained significant attention from researchers. Nanotechnology has revolutionized the BTE field due to the possibility of generating nanoengineered particles that are able to overcome the current limitations in regenerative strategies, including reduced cell proliferation and differentiation, the inadequate mechanical strength of biomaterials, and poor production of extrinsic factors which are necessary for efficient osteogenesis. In this review, we report on the latest in vitro and in vivo studies on the impact of nanotechnology in the field of BTE, focusing on the effects of nanoparticles on the properties of cells and the use of biomaterials for bone regeneration. [ABSTRACT FROM AUTHOR]

O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D--binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine. Vitamin D plays an essential role in mineral homeostasis and its deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. We therefore set out to examine the effects of the loss of Galnt11 on vitamin D homeostasis and bone composition. We found significantly decreased levels of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, consistent with decreased reabsorption of DBP. This was accompanied by a significant reduction in blood calcium levels and a physiologic increase in parathyroid hormone (PTH) in Galnt11-deficient mice. Bones in Galnt11-deficient mice were smaller and displayed a decrease in cortical bone accompanied by an increase in trabecular bone and an increase in a marker of bone formation, consistent with PTH-mediated effects on bone. These results support a unified model for the role of Galnt11 in bone and mineral homeostasis, wherein loss of Galnt11 leads to decreased reabsorption of DBP by megalin, resulting in a cascade of disrupted mineral and bone homeostasis including decreased circulating vitamin D and calcium levels, a physiological increase in PTH, an overall loss of cortical bone, and an increase in trabecular bone. Our study elucidates how defects in O-glycosylation can influence vitamin D and mineral homeostasis and the integrity of the skeletal system. [ABSTRACT FROM AUTHOR]

Background: Shoulder disorders, particularly rotator cuff tears, are prevalent musculoskeletal conditions related to aging. Although the widely used suture anchor technique provides strong mechanical support to the tendon, it is associated with a risk of postoperative tendon retearing. The conventionally used titanium alloys can affect the interpretation of magnetic resonance imaging. Degradable magnesium alloys possess excellent biocompatibility, similar mechanical property to the bone, and stimulating bone formation ability from Mg2+. The purpose of this experiment was to develop innovative magnesium-based suture anchors to enhance rotator cuff repair by improving fixation materials, and to evaluate their feasibility in a goat model. Methods: We developed fluoridized ZK60 suture anchors as the implantation material for two goats, who underwent rotator cuff repair surgery on both shoulders. Computed tomography (CT) and histological analysis were performed at 12 weeks postoperatively, and the results were compared between the magnesium and titanium alloy groups. Additionally, a hematological examination was conducted, which included assessments of red blood cells, white blood cells, platelets, coagulation function, liver function, kidney function, and magnesium ion concentration. Results: The 12-week postoperative CT images showed intact MgF2 ZK60 suture anchors, effectively reconnecting the infraspinatus tendon to the humeral head. The anchors became less visible on CT scans, indicating absorption by surrounding tissues. New bone formation in the MgF2 group surpassed that in the Ti group, demonstrating superior osseointegration. The similarity between cortical bone and magnesium reduced stress-shielding and promoted bone regeneration. Histological analysis revealed successful tendon healing with MgF2 anchors, while the Ti group showed discontinuous interfaces and reduced collagen secretion. Hematological examination showed stable liver, renal function, and magnesium ion levels. Conclusions: The findings indicate that MgF2-coated suture anchors are feasible for rotator cuff repair and potentially other orthopedic applications. We hope that magnesium alloy anchors can become the solution for rotator cuff tendon repair surgery. [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]

Open-cell foams based on hydroxyapatite (HAp) can mimic the extracellular matrix (ECM) to better replace damaged hard tissues and assist in their regeneration processes. Aerogels of HAp nanowires (NW) with barium titanate (BT) particles were produced and characterized regarding their physical and chemical properties, bioactivity, and in vitro cytotoxicity. Considering the role of piezoelectricity (mainly due to collagen) and surface charges in bone remodeling, all BT particles, of size 280 nm and 2 and 3 µm, contained BaTiO3 in their piezoelectric tetragonal phase. The synthesized nanowires were verified to be AB-type carbonated hydroxyapatite. The aerogels showed high porosity and relatively homogeneous distribution of the BT particles. Barium titanate proved to be non-cytotoxic while all the aerogels produced were cytotoxic for an extract concentration of 1 mg/mL but became non-cytotoxic at concentrations of 0.5 mg/mL and below. It is possible that these results were affected by the higher surface area and quicker dissolution rate of the aerogels. In the bioactivity assays, SEM/EDS, it was not easy to differentiate between the apatite deposition and the surface of the HAp wires. However, a quantitative EDS analysis shows a possible CaP deposition/dissolution cycle taking place. [ABSTRACT FROM AUTHOR]

Polysaccharide-based membranes with excellent mechanical properties are highly desired. However, severe mechanical deterioration under wet conditions limits their biomedical applications. Here, inspired by the structural heterogeneity of strong yet hydrated biological materials, we propose a strategy based on heterogeneous crosslink-and-hydration (HCH) of a molecule/nano dual-scale network to fabricate polysaccharide-based nanocomposites with robust wet mechanical properties. The heterogeneity lies in that the crosslink-and-hydration occurs in the molecule-network while the stress-bearing nanofiber-network remains unaffected. As one demonstration, a membrane assembled by bacterial cellulose nanofiber-network and Ca2+-crosslinked and hydrated sodium alginate molecule-network is designed. Studies show that the crosslinked-and-hydrated molecule-network restricts water invasion and boosts stress transfer of the nanofiber-network by serving as interfibrous bridge. Overall, the molecule-network makes the membrane hydrated and flexible; the nanofiber-network as stress-bearing component provides strength and toughness. The HCH dual-scale network featuring a cooperative effect stimulates the design of advanced biomaterials applied under wet conditions such as guided bone regeneration membranes. [ABSTRACT FROM AUTHOR]

The effect of surface modification by an arc discharge plasma in a nitrogen flow with treatment durations of 5 and 10 min on the physicochemical properties and biocompatibility of the surface of composites based on polylactic acid and hydroxyapatite (PLA/HA) with different mass ratios (80/20, 70/30, 60/40) has been investigated. The aim of this work was to show the correlation between the changes of the physicochemical characteristics (chemical compound, morphology, wettability) of the surface layer of the PLA/HA composites and the cell viability (macrophages) in the presence of the plasma-modified materials. The dependence of alterations of the functional properties (wettability, biocompatibility) on the change in the chemical composition under the plasma exposure has been established. The chemical composition was studied using X-ray photoelectron spectroscopy (XPS), the surface morphology was researched with scanning electron microscopy (SEM), and the wettability of the composite's surface was analyzed by measuring the contact angle and surface energy calculation. In addition, the viability of macrophages was investigated when the macrophages from three donors interacted with a modified PLA/HA surface. It was found that the formation of the new functional groups, –C-N and N-C=O/C=O, improves the wettability of the surface of the composites and promotes the viability of macrophages in the presence of the composite materials. The fundamental principles for obtaining promising materials with the required properties for eliminating bone defects have been created. [ABSTRACT FROM AUTHOR]

Bovine bone is an animal‐origin matrix rich in type I collagen (COL I) and it necessitates prior demineralization and makes COL I available. This study investigated the ossein–hydroxyapatite physicochemical properties evaluation as a result of processing and solubilization by acids and revealed the bone matrix demineralization and making COL I available. The tibia residue from bovine sources was processed, ground, and transformed into bone matrix powder. The bone matrix was solubilized in acetic acid followed by lactic acid. The bone matrix was evaluated as a result of processing and solubilization by acids: ossein and hydroxyapatite percentages by nitrogen and ash content, mineral content, particle size distribution, Fourier‐transformation infrared spectroscopy, x‐ray diffraction, and scanning electron microscope. For the obtained residual extracts, pH and mineral content were evaluated. The solubilization by acids affected the ossein–hydroxyapatite physicochemical properties, and the bone matrix solubilized by acetic and lactic acid showed the preservation of the ossein alongside the loss of hydroxyapatite. The processing and the solubilization by acids were revealed to be a alternative to bone matrix demineralization and enabling the accessibility of bone COL I. Practical Application: Bovine bone is an abundant type I collagen source, but processing maneuvers and demineralization effect present limitations due to the rigidity of the structural components. Exploring methodologies to process and demineralize will allow type I collagen to be obtained from the bone source, and direct and amplify the potentialities in the chemical and food industries. The research focused on bone sources and collagen availability holds paramount significance, and promotes repurposing agribusiness residues and development of protein–base products. [ABSTRACT FROM AUTHOR]

Piezoelectric biomaterials can generate piezoelectrical charges in response to mechanical activation. These generated charges can directly stimulate bone regeneration by triggering signaling pathway that is important for regulating osteogenesis of cells seeded on the materials. On the other hand, mechanical forces applied to the biomaterials play an important role in bone regeneration through the process called mechanotransduction. While mechanical force and electrical charges are both important contributing factors to bone tissue regeneration, they operate through different underlying mechanisms. The utilizations of piezoelectric biomaterials have been explored to serve as self-charged scaffolds which can promote stem cell differentiation and the formation of functional bone tissues. However, it is still not clear how mechanical activation and electrical charge act together on such a scaffold and which factors play more important role in the piezoelectric stimulation to induce osteogenesis. In our study, we found Poly(l-lactic acid) (PLLA)-based piezoelectric scaffolds with higher piezoelectric charges had a more pronounced osteoinductive effect than those with lower charges. This provided a new mechanistic insight that the observed osteoinductive effect of the piezoelectric PLLA scaffolds is likely due to the piezoelectric stimulation they provide, rather than mechanical stimulation alone. Our findings provide a crucial guide for the optimization of piezoelectric material design and usage. [ABSTRACT FROM AUTHOR]

Lithium disilicate (LD) glass-ceramics have adequate mechanical properties and are considered as a candidate for repairing large bone defects. However, LD glass-ceramic is an inherently inert restorative material, which cannot induce new bone tissue. In the present study, LD glass-ceramics were ion-exchanged at 235 °C for 16 h, 64 h and 128 h in a mixed salt bath of sodium nitrate and potassium nitrate (1:1 M ratio) respectively. A gradient concentration distribution of Na+-rich layer was obtained by Li+/Na+ exchange and Na+ ions were released from the Li+/Na+ exchanged LD glass-ceramics in an aqueous condition. The hydroxyapatite (HA) layer was formed on Li+/Na+ exchanged LD glass-ceramic and exhibited a significant exchange time-dependent after soaking in the simulated body fluid (SBF). Moreover, the Li+/Na+ exchange treatment could improve cell adhesion, proliferation and osteogenic differentiation of LD glass-ceramic significantly, and long-time treatment could achieve a better performance. Therefore, ion-exchange process is a feasible strategy to promote the surface biomineralization, cytocompatibility and osteogenesis of LD glass-ceramics. These results suggest that Li+/Na+ exchange is a promising process for LD glass-ceramic application in clinical orthopedic reconstruction. [ABSTRACT FROM AUTHOR]

Magnesium oxychloride cement (MOC) has been selected as a promising material for bone repair materials due to its prominent mechanical properties and non-toxicity towards mesenchymal stem cells. However, the limited water resistance of traditional MOC constrains its application range. Accordingly, this study investigated the impact of phytic acid (PA) on the mechanical properties, water resistance, and handling properties of MOC as a biomaterial, utilizing various macroscopic and microscopic characterization techniques. The results demonstrated that PA can enhance the mechanical strength and water resistance of MOC. Furthermore, multiple microscopic methods were employed to analyze the mechanism underlying the PA modification of MOC. These findings revealed that the insoluble gel-like structure was wrapped on the surface of the phase 5 crystals, which prevented the intrusion of water and improved the water resistance of MOC. Incorporating PA improved the injectability and degradability of MOC. Therefore, the development of this modified MOC provides a promising strategy for its application as a bone repair material. [ABSTRACT FROM AUTHOR]

The development of cellular materials with adjustable mechanical properties, total porosity (Tp), and elastic modulus (E) similar to those of natural bone are eternal pursuits in the field of bone implants. Designing and manufacturing an implant that fulfills all these requirements is a challenging task. In this study, inspired by the trabecular structure of natural bone and developed a biomimetic structural material. Laser powder bed fusion (L‐PBF) is utilized to create the biomimetic structural material. Comprehensive valuations of both the natural trabecular bone and biomimetic structural material are conducted using micro‐CT scanning, nanoindentation testing, finite element (FE) analysis, and compression testing. The results demonstrate that the mechanical properties of the developed biomimetic structural material have excellent controllability. The rod‐plate‐like trabecular (RPT) biomimetic structural material exhibited significantly superior mechanical load‐bearing performance compared to the natural bone trabeculae while maintaining the natural bone's Tp (83.1%) and E (798.1 MPa). The biomimetic structural material effectively balances the combination of strength and E, providing a design template for the next generation of medical implants. It has great potential as a bone repair material for clinical applications, and its adjustable mechanical properties also make it highly promising in the field of tissue engineering. [ABSTRACT FROM AUTHOR]

Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices' patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17β-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study. [ABSTRACT FROM AUTHOR]

Effective filling materials, typically bone cements, are essential for providing mechanical support during bone fracture treatment. A current challenge with bone cement lies in achieving continuous drug release and forming porous structures that facilitate cell migration and enhance osteoconductivity. We report a droplet microfluidics-based method for synthesizing uniform-sized gelatin hydrogel beads. A high hydrogel concentration and increased crosslinking levels were found to enhance drug loading as well as release performance. Consequently, the droplet microfluidic device was optimized in its design and fabrication to enable the stable generation of uniform-sized droplets from high-viscosity gelatin solutions. The size of the generated beads can be selectively controlled from 50 to 300 μm, featuring a high antibiotic loading capacity of up to 43% dry weight. They achieve continuous drug release lasting more than 300 h, ensuring sustained microbial inhibition with minimal cytotoxicity. Furthermore, the hydrogel beads are well suited for integration with calcium phosphate cement, maintaining structural integrity to form porous matrices and improve continuous drug release performance. The uniform size distribution of the beads, achieved through droplet microfluidic synthesis, ensures predictable drug release dynamics and a measurable impact on the mechanical properties of bone cements, positioning this technology as a promising enhancement to bone cement materials. [ABSTRACT FROM AUTHOR]

The progress in artificial bone research is crucial for addressing fractures and bone defects in the aging population. However, challenges persist in terms of biocompatibility and structural complexity. Nanotechnology provides a promising avenue by which to overcome these challenges, with nano-ferrite particles (NFPs) exhibiting superparamagnetic properties. The ability to control cell positioning using a magnetic field opens up new possibilities for customizing artificial bones with specific shapes. This study explores the biological effects of NFPs on osteoblast-like cell lines (MC3T3-E1), including key analyses, such as cell viability, cellular uptake of NFPs, calcification processes, cell migration under external magnetic field conditions, and three-dimensional modeling. The results indicate that the impact of NFPs on cell proliferation is negligible. Fluorescence and transmission electron microscopy validated the cellular uptake of NFPs, demonstrating the potential for precise cell positioning through an external magnetic field. Under calcification-inducing conditions, the cells exhibited sustained calcification ability even in the presence of NFPs. The cell movement analysis observed the controlled movement of NFP-absorbing cells under an external magnetic field. Applying a magnetic field along the z-axis induced the three-dimensional shaping of cells incorporating NFPs, resulting in well-arranged z-axis directional patterns. In this study, NFPs demonstrated excellent biocompatibility and controllability under an external magnetic field, laying the foundation for innovative treatment strategies for customizing artificial bones. [ABSTRACT FROM AUTHOR]

Forensic anthropologists play a key role in skeletal trauma analysis and commonly use macroscopic features to distinguish between trauma types. However, this approach can be challenging, particularly in cases of highly comminuted or incompletely recovered fractures. Histological analysis of microscopic fracture characteristics in fractured bones may thus help provide additional information on trauma type and bone fracture biomechanics in general. This study analysed the extent of microcrack damage to osteons in long bones with blunt force trauma (BFT) and gunshot trauma (GST), from both traumatic death cases and post-mortem experimental fractures. We identified four types of osteonal damage (OD). In traumatic death cases, OD affecting the inside of the osteon and compromising the Haversian canal (type 1) was found to be indicative of BFT. Moreover, OD affecting the cement line (type 3) and interstitial lamellae (type 4) was more common in the GST samples. OD affecting the inside of the osteon without compromising the Haversian canal (type 2) was not found to be indicative of either trauma type. In cases of experimental fractures, our study revealed that post-mortem fractures in dry bone samples featured the highest amount of OD, particularly of type 4. This study also found that the experimentally produced GST featured similar OD patterns to GST death cases. These findings support our hypothesis that there are distinct osteonal damage patterns in human long bones with BFT and GST, which are of relevant value for trauma analysis in forensic anthropology. [ABSTRACT FROM AUTHOR]

Bone loss in lower limbs under space microgravity condition can persist even after the astronauts return to Earth's gravitational environment. It is crucial to determine the extent and timing of bone recovery after spaceflight, especially for long-term flights. However, there is a lack of comprehensive descriptions of the recovery of various aspects of bone quality, particularly in terms of compositional characteristics that reflect changes in bone quality. Therefore, the objective of this study is to investigate the alterations in bone mineral density, composition characteristics, and mechanical properties of rat lower limbs during unloading (tail suspension) and the subsequent recovery loading period. Rats were subjected to tail suspension for four weeks (TS4) followed by reloading for an additional four weeks. Bone mineral density (BMD) was measured by μ-CT and analyzed. The mechanical properties of the tibia were assessed by a three-point bending test, and the composition characteristics of bone tissue were evaluated using Raman spectroscopy. Regression analysis was performed to identify main component related to mechanical property. In the metaphysis, BMD of the tibia significant decreased, particularly in trabecular bone. Upon reloading, only the cortical bone showed recovery. In the diaphysis, cortical bone remained unchanged during unloading but demonstrated delayed bone loss during the reloading period. Simultaneously, the mechanical properties of tibia experienced a substantial reduction after four weeks of unloading, The stiffness and maximum strength did not fully recover, though the elastic modulus and the ultimate strength were restored following the reloading process. Raman spectroscopy characterization found an increase in the carbonate substitution and crystal crystallinity of the diaphysis after 4 weeks of unloading. There was an intriguing alteration in the mineralized collagen ratio, that an increase was observed in the diaphysis while a decrease was observed in the metaphysis. During 4 weeks of reloading, the compositional characteristics of the diaphysis recovered earlier than those of the metaphysis, with the exception of crystallinity which remained unrecovered. Regression analysis indicated that carbonate replacement has a strong correlation to bone mechanical properties during the 4 weeks of unloading and subsequent 4 weeks of reloading. The data obtained in this study highlight the incomplete recovery of bone mineral density, mechanical properties, and compositional characteristics during reloading in tail-suspended rats. These findings deepen our understanding of microgravity-induced bone loss and provide valuable information to develop interventions not only for astronauts but also for persons on earth during and after prolonged periods of unloading. • Cortical and cancellous bone exhibit distinct responses to gravitational forces. • The components of load-bearing bone do not immediately recover after recovery from gravity. • The substitution of carbonate during periods of reloading is highly associated with the mechanical properties of bone. [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]

In the field of bone tissue engineering, which is being developed for the ideal restoration of bone defects, researchers are exploring the improvement of the bone regeneration efficacy of scaffolds through various approaches involving osteoconductive, osteoinductive, and angiogenic factors. In the current trend of research, there is also a suggestion that the topological factors of recent scaffolds may influence the attachment, migration, proliferation, and differentiation of bone cells. Building upon experimental confirmation of the effect of scaffold conformity with the defect site on enhanced bone regeneration in previous studies, we conducted this research to experimentally investigate the relationship between contact area with the defect site and bone regeneration efficacy. The results demonstrated that as the contact area of the scaffold increased, not only did the resistance to bone tissue growth increase, more significant bone regeneration also occurred, as evidenced through histological analysis and micro-CT analysis. This research confirms that the contact area between the scaffold and the defect site is a critical variable affecting bone regeneration efficacy, emphasizing its importance when designing customized scaffolds. This finding holds promising implications for future studies and applications in the field. [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]

[Display omitted] Bioceramics have been extensively used to improve osteogenesis of polymers because of their excellent bone-forming capabilities. However, the inadequate interfacial bonding between ceramics and polymers compromises their mechanical properties. In this study, zeolitic imidazolate framework-8 (ZIF-8) was grown in situ on strontium carbonate (SrCO 3) to construct a core–shell SrCO 3 @ZIF-8, which was then added to poly- l -lactic acid (PLLA) to print a SrCO 3 @ZIF-8/PLLA composite scaffold using selective sintering technology. First, ZIF-8 characterized by its multiple organic ligands, forms a robust interface with PLLA. Second, SrCO 3 characterized by its negative zeta potential in solution, exhibits the ability to adsorb positively charged zinc ions. This, in turn, promotes the in situ growth of ZIF-8 on SrCO 3 , eventually achieving perfect bonding between the second phase and the PLLA matrix. Our findings indicated that the composite scaffold exhibited the highest compressive strength (21.93 MPa) and significantly promoted the osteogenic differentiation of mouse mesenchymal stem cells. Moreover, the in vivo results established that the SrCO 3 @ZIF-8/PLLA scaffold significantly accelerated bone regeneration efficiency in rat femur defects. The prepared scaffold, with its favorable mechanical properties and osteogenic activity, shows considerable promise for applications in bone repair. [ABSTRACT FROM AUTHOR]