Interstitial Fluid Shear Stress Induces the Synthetic Phenotype Switching of VSMCs to Release Pro-calcified Extracellular Vesicles via EGFR-MAPK-KLF5 Pathway.

Phenotypic switching (from contractile to synthetic) of vascular smooth muscle cells (VSMCs) is essential in the progression of atherosclerosis. The damaged endothelium in the atherosclerotic artery exposes VSMCs to increased interstitial fluid shear stress (IFSS). However, the precise mechanisms by which increased IFSS influences VSMCs phenotypic switching are unrevealed. Here, we employed advanced numerical simulations to calculate IFSS values accurately based on parameters acquired from patient samples. We then carefully investigated the phenotypic switching and extracellular vesicles (EVs) secretion of VSMCs under various IFSS conditions. By employing a comprehensive set of approaches, we found that VSMCs exhibited synthetic phenotype upon atherosclerotic IFSS. This synthetic phenotype is the upstream regulator for the enhanced secretion of pro-calcified EVs. Mechanistically, as a mechanotransducer, the epidermal growth factor receptor (EGFR) initiates the flow-based mechanical cues to MAPK signaling pathway, facilitating the nuclear accumulation of the transcription factor krüppel-like factor 5 (KLF5). Furthermore, pharmacological inhibiting either EGFR or MAPK signaling pathway blocks the nuclear accumulation of KLF5 and finally results in the maintenance of contractile VSMCs even under increased IFSS stimulation. Collectively, targeting this signaling pathway holds potential as a novel therapeutic strategy to inhibit VSMCs phenotypic switching and mitigate the progression of atherosclerosis.

Analysis of cartilage loading and injury correlation in knee varus deformity.

Knee varus (KV) deformity leads to abnormal forces in the different compartments of the joint cavity and abnormal mechanical loading thus leading to knee osteoarthritis (KOA). This study used computer-aided design to create 3-dimensional simulation models of KOA with varying varus angles to analyze stress distribution within the knee joint cavity using finite element analysis for different varus KOA models and to compare intra-articular loads among these models. Additionally, we developed a cartilage loading model of static KV deformity to correlate with dynamic clinical cases of cartilage injury. Different KV angle models were accurately simulated with computer-aided design, and the KV angles were divided into (0°, 3°, 6°, 9°, 12°, 15°, and 18°) 7 knee models, and then processed with finite element software, and the Von-Mises stress distribution and peak values of the cartilage of the femoral condyles, medial tibial plateau, and lateral plateau were obtained by simulating the human body weight in axial loading while performing the static extension position. Finally, intraoperative endoscopy visualization of cartilage injuries in clinical cases corresponding to KV deformity subgroups was combined to find cartilage loading and injury correlations. With increasing varus angle, there was a significant increase in lower limb mechanical axial inward excursion and peak Von-Mises stress in the medial interstitial compartment. Analysis of patients' clinical data demonstrated a significant correlation between varus deformity angle and cartilage damage in the knee, medial plateau, and patellofemoral intercompartment. Larger varus deformity angles could be associated with higher medial cartilage stress loads and increased cartilage damage in the corresponding peak stress area. When the varus angle exceeds 6°, there is an increased risk of cartilage damage, emphasizing the importance of early surgical correction to prevent further deformity and restore knee function.

Finite element analysis of the effect of tibial osteotomy on the stress of polyethylene liner in total knee arthroplasty.

AIM: To explore the effects of tibial osteotomy varus angle combined with posterior tibial slope (PTS) on the stress of polyethylene liner in total knee arthroplasty (TKA) by building finite element model (FEM). METHODS: Established the FEM of standard TKA with tibial osteotomy varus angle 0° to 9° were established and divided into 10 groups. Next, each group was created 10 FEMs with 0° to 9° PTS separately. Calculated the stress on polyethylene liner in each group in Abaqus. Finally, the relevancy between tibial osteotomy angle and polyethylene liner stress was statistically analyzed using multiple regression analysis. RESULTS: As the varus angle increased, the area of maximum stress gradually shifted medially on the polyethylene liner. As the PTS increases, the percentage of surface contact forces on the medial and lateral compartmental of the polyethylene liner gradually converge to the same. When the varus angle is between 0° and 3°, the maximum stress of the medial compartmental surfaces of polyethylene liner rises smoothly with the increase of the PTS. When the varus angle is between 4° and 9°, as the increase of the PTS, the maximum stress of polyethylene liner rises first and then falls, forming a trough at PTS 5° and then rises again. Compared to the PTS, the varus angle has a large effect on the maximum stress of the polyethylene liner (p < .001). CONCLUSION: When the varus angle is 0° to 3°, PTS 0° is recommended, which will result in a more equalized stress distribution of the polyethylene liner in TKA.

Evaluating flexure properties, hardness, roughness and microleakage of high-strength injectable dental composite: an in vitro study.

BACKGROUND: Recently, a new generation of high-strength flowable dental composites has been introduced by manufacturers. The manufacturers claim that these materials have enhanced mechanical and physical properties and are suitable for use in a wide range of direct anterior and posterior restorations, even in high-stress bearing areas. AIM: The objective of this study was to assess certain physical and mechanical properties of these recently introduced high-strength flowable composites in comparison to conventional multipurpose dental composites. METHODS: Four types of high-strength flowable composites (Genial Universal FLO, Gaenial Universal Injectable, Beautifil Injectable, and Beautifil Flow Plus) were tested in experimental groups, while a nanohybrid conventional composite (Filtek Z350 XT) was used as the control. For flexure properties, ten rectangular samples (2 × 2 × 25 mm) were prepared from each composite material and subjected to 5000 cycles of thermocycling. Samples were then subjected to flexural strength testing using the universal testing machine. Another twenty disc-shaped specimens of dimensions (5 mm diameter × 2 mm thickness) were fabricated from each composite material for surface roughness (Ra) (n = 10) and hardness (VHN) test (n = 10). All samples underwent 5000 cycles of thermocycling before testing. Additionally, microleakage testing was conducted on 60 standardized class V cavities prepared on molar teeth and divided randomly into five groups (n = 12). Cavities were then filled with composite according to the manufacturer's instructions and subjected to thermocycling for 1000 cycles before testing using methylene blue solution and a stereomicroscope. RESULTS: All tested materials were comparable to the control group in terms of flexural strength and surface roughness (p > 0.05), with Gaenial Universal FLO exhibiting significantly higher flexural strength compared to the other flowable composite materials tested. However, all tested materials demonstrated significantly lower elastic modulus and surface hardness than the control group (p < 0.05). The control group exhibited higher microleakage scores, while the lowest scores were observed in the Gaenial Universal FLO material (p < 0.05) CONCLUSION: The physical and mechanical behaviors of the different high-strength flowable composites investigated in this study varied. Some of these materials may serve as suitable alternatives to conventional composites in specific applications, emphasizing the importance of dentists being familiar with material properties before making material selections.

Analysis of prefabricated myofunctional appliances with different overjet and bumper designs: a three-dimensional finite element analysis.

BACKGROUND: Prefabricated myofunctional appliance can guide tooth eruption, improve dentition alignment, correct myofunctional disorders and harmful oral habits. However, its application to skeletal discrepancy may result in unsatisfactory tooth inclination. This study aimed to construct a novel appliance with overjet design to avoid this side effect and investigated its shape and mechanical changes under occlusion using three-dimensional finite element method. METHODS: We established three samples of prefabricated myofunctional appliances. The first one was edge to edge without overjet, and the outer shield of both jaws were flattened. The second one was 3 mm overjet with stepped the outer shield. The last one was 3 mm overjet, and the outer shield of both jaws were flatted, which meant the front wall of lower jaw was strengthened with bumper, termed as lower bumper. A complete dentition model was applied to the study. 150 N occlusal force was applied to each type of appliance and the deformation displacement and the changes in stress was recorded. RESULTS: The deformation was significant in the incisors regions, especially in the vertical and lateral dimensions. The maximum displacements of 3 mm overjet with step shield group were 7.08 mm (vertical), 3.99 mm (lateral), and 2.90 mm (sagittal), while it decreased to 3.92 mm(vertical), 1.94 mm (lateral), and 1.55 mm (sagittal) in overjet with bumper group. Moreover, the upper molar regions exhibited higher vertical and sagittal displacement in 3 mm overjet with step shield group, which were 3.03 mm (vertical) and 1.99 mm (sagittal), and the bumper design could decrease the maximum displacement to 1.72 mm (vertical) and 0.72 mm (sagittal). In addition, the Von Mises stress of appliances was analyzed, and results indicated that 3 mm overjet with step shield generated higher stress than other groups, with the maximum Von Mises stress was 0.9387 MP, which were 0.5858 and 0.5657 MP in edge to edge group and 3 mm overjet with lower bumper group, respectively. CONCLUSION: The prefabricated myofunctional appliances may cause deformation during occlusion. Compared to step shield group, the application of lower bumper exhibited better resistance to occlusal force.

Shear stress and pathophysiological PI3K involvement in vascular malformations.

Molecular characterization of vascular anomalies has revealed that affected endothelial cells (ECs) harbor gain-of-function (GOF) mutations in the gene encoding the catalytic α subunit of PI3Kα (PIK3CA). These PIK3CA mutations are known to cause solid cancers when occurring in other tissues. PIK3CA-related vascular anomalies, or "PIKopathies," range from simple, i.e., restricted to a particular form of malformation, to complex, i.e., presenting with a range of hyperplasia phenotypes, including the PIK3CA-related overgrowth spectrum. Interestingly, development of PIKopathies is affected by fluid shear stress (FSS), a physiological stimulus caused by blood or lymph flow. These findings implicate PI3K in mediating physiological EC responses to FSS conditions characteristic of lymphatic and capillary vessel beds. Consistent with this hypothesis, increased PI3K signaling also contributes to cerebral cavernous malformations, a vascular disorder that affects low-perfused brain venous capillaries. Because the GOF activity of PI3K and its signaling partners are excellent drug targets, understanding PIK3CA's role in the development of vascular anomalies may inform therapeutic strategies to normalize EC responses in the diseased state. This Review focuses on PIK3CA's role in mediating EC responses to FSS and discusses current understanding of PIK3CA dysregulation in a range of vascular anomalies that particularly affect low-perfused regions of the vasculature. We also discuss recent surprising findings linking increased PI3K signaling to fast-flow arteriovenous malformations in hereditary hemorrhagic telangiectasias.

Biomechanical impact of different isthmus positions in mandibular first molar root canals: a finite element analysis.

OBJECTIVE: This study used image-based finite element analysis (FEA) to assess the biomechanical changes in mandibular first molars resulting from alterations in the position of the root canal isthmus. METHODS: A healthy mandibular first molar, characterized by two intact root canals and a cavity-free surface, was selected as the subject. A three-dimensional model for the molar was established using scanned images of the patient's mandibular teeth. Subsequently, four distinct finite element models were created, each representing varied root canal morphologies: non-isthmus (Group A), isthmus located at the upper 1/3 of the root (Group B), middle 1/3 of the root (Group C), and lower 1/3 of the root (Group D). A static load of 200 N was applied along the tooth's longitudinal axis on the occlusal surface to simulate regular chewing forces. The biomechanical assessment was conducted regarding the mechanical stress profile within the root dentin. The equivalent stress (Von Mises stress) was used to assess the biomechanical features of mandibular teeth under mechanical loading. RESULTS: In Group A (without an isthmus), the maximum stress was 22.2 MPa, while experimental groups with an isthmus exhibited higher stresses, reaching up to 29.4 MPa. All maximum stresses were concentrated near the apical foramen. The presence of the isthmus modified the stress distribution in the dentin wall of the tooth canal. Notably, dentin stresses at specific locations demonstrated differences: at 8 mm from the root tip, Group B: 13.6 MPa vs. Group A: 11.4 MPa; at 3 mm from the root tip, Group C: 14.2 MPa vs. Group A: 4.5 MPa; at 1 mm from the root tip, Group D: 25.1 MPa vs. Group A: 10.3 MPa. The maximum stress in the root canal dentin within the isthmus region was located either at the top or bottom of the isthmus. CONCLUSION: A root canal isthmus modifies the stress profile within the dentin. The maximum stress occurs near the apical foramen and significantly increases when the isthmus is located closer to the apical foramina.

Interface stress transfer model and modulus parameter equivalence method for composite materials embedded with tensile pre-strain shape memory alloy fibers.

The constitutive model and modulus parameter equivalence of shape memory alloy composites (SMAC) serve as the foundation for the structural dynamic modeling of composite materials, which has a direct impact on the dynamic characteristics and modeling accuracy of SMAC. This article proposes a homogenization method for SMA composites considering interfacial phases, models the interface stress transfer of three-phase cylinders physically, and derives the axial and shear stresses of SMA fiber phase, interfacial phase, and matrix phase mathematically. The homogenization method and stress expression were then used to determine the macroscopic effective modulus of SMAC as well as the stress characteristics of the fiber phase and interface phase of SMA. The findings demonstrate the significance of volume fraction and tensile pre-strain in stress transfer between the fiber phase and interface phase at high temperatures. The maximum axial stress in the fiber phase is 705.05 MPa when the SMA is fully austenitic and the pre-strain increases to 5%. At 10% volume fraction of SMA, the fiber phase's maximum axial stress can reach 1000 MPa. Ultimately, an experimental verification of the theoretical calculation method's accuracy for the effective modulus of SMAC lays the groundwork for the dynamic modeling of SMAC structures.

Investigating the effect of anatomical variations in the response of the neonatal brachial plexus to applied force: Use of a two-dimensional finite element model.

The brachial plexus is a set of nerves that innervate the upper extremity and may become injured during the birthing process through an injury known as Neonatal Brachial Plexus Palsy. Studying the mechanisms of these injuries on infant cadavers is challenging due to the justifiable sensitivity surrounding testing. Thus, these specimens are generally unavailable to be used to investigate variations in brachial plexus injury mechanisms. Finite Element Models are an alternative way to investigate the response of the neonatal brachial plexus to loading. Finite Element Models allow a virtual representation of the neonatal brachial plexus to be developed and analyzed with dimensions and mechanical properties determined from experimental studies. Using ABAQUS software, a two-dimensional brachial plexus model was created to analyze how stresses and strains develop within the brachial plexus. The main objectives of this study were (1) to develop a model of the brachial plexus and validate it against previous literature, and (2) to analyze the effect of stress on the nerve roots based on variations in the angles between the nerve roots and the spinal cord. The predicted stress for C5 and C6 was calculated as 0.246 MPa and 0.250 MPa, respectively. C5 and C6 nerve roots experience the highest stress and the largest displacement in comparison to the lower nerve roots, which correlates with clinical patterns of injury. Even small (+/- 3 and 6 degrees) variations in nerve root angle significantly impacted the stress at the proximal nerve root. This model is the first step towards developing a complete three-dimensional model of the neonatal brachial plexus to provide the opportunity to more accurately assess the effect of the birth process on the stretch within the brachial plexus and the impact of biological variations in structure and properties on the risk of Neonatal Brachial Plexus Palsy.

Analysis of sinusoidal post-buckling deformation of horizontal coiled tubing with initial residual bending.

In the process of horizontal well construction, the working environment in the well is very complicated. It is difficult to determine the actual deformation and force of the coiled tubing in the wellbore from the load change at the wellhead along. In addition, the coiled tubing wrapped around the reel and entering the wellbore through the injection head may cause an initial residual bending. In this paper, the mathematical model of the coiled tubing under axial load during buckling deformation is established, and the analytical solution with the time term is derived by reasonable simplification of the model. The effect of residual bending on the post-sinusoidal buckling of the coiled tubing in the horizontal well was investigated using the separation variable method. The effect of residual bending variations on the well wall contact forces is analyzed. The research shows that the initial parameter Г is the main factor influencing the post-sinusoidal buckling of the coiled tubing with residual bending. The larger the parameter value Г, the greater the effect of the residual bending on the post-sinusoidal buckling deformation of the coiled tubing, and the earlier the critical point of the mixed sinusoidal-helical buckling of the coiled tubing appears. The compression velocity of the coiled tubing has a significant effect on the well wall contact force. The faster the compression, the greater the contact force. By introducing the time term and the separation variable, this paper provides a new method and theoretical basis for further study of the process of entering sinusoidal-helical buckling of the coiled tubing with initial residual bending.

Compositional, Structural, and Biomechanical Properties of Three Different Soft Tissue-Hard Tissue Insertions: A Comparative Review.

Connective tissue attaches to bone across an insertion with spatial gradients in components, microstructure, and biomechanics. Due to regional stress concentrations between two mechanically dissimilar materials, the insertion is vulnerable to mechanical damage during joint movements and difficult to repair completely, which remains a significant clinical challenge. Despite interface stress concentrations, the native insertion physiologically functions as the effective load-transfer device between soft tissue and bone. This review summarizes tendon, ligament, and meniscus insertions cross-sectionally, which is novel in this field. Herein, the similarities and differences between the three kinds of insertions in terms of components, microstructure, and biomechanics are compared in great detail. This review begins with describing the basic components existing in the four zones (original soft tissue, uncalcified fibrocartilage, calcified fibrocartilage, and bone) of each kind of insertion, respectively. It then discusses the microstructure constructed from collagen, glycosaminoglycans (GAGs), minerals and others, which provides key support for the biomechanical properties and affects its physiological functions. Finally, the review continues by describing variations in mechanical properties at the millimeter, micrometer, and nanometer scale, which minimize stress concentrations and control stretch at the insertion. In summary, investigating the contrasts between the three has enlightening significance for future directions of repair strategies of insertion diseases and for bioinspired approaches to effective soft-hard interfaces and other tough and robust materials in medicine and engineering.

Biomechanical changes in the proximal femur before and after removal of femoral neck system.

BACKGROUND: As an innovative internal fixation system, FNS (femoral neck system) is increasingly being utilized by surgeons for the treatment of femoral neck fractures. At present, there have been numerous finite element analysis experiments studying the immediate stability of FNS and CSS in treating femoral neck fractures. However, there is scarce mechanical analysis available regarding the effects post internal fixation removal. This study aimed to investigate the alterations in mechanical parameters of the proximal femur before and after the removal of FNS (femoral neck system), and to assess potential distinctions in indicators following the extraction of CSS (Cannulated Screws). METHODS: A proximal femur model was reconstructed using finite element numerical techniques. The models for CSS and FNS were formulated utilizing characteristics and parametric definitions. The internal fixation was combined with a normal proximal femur model to simulate the healing state after fracture surgery. Within the framework of static analysis, consistent stress burdens were applied across the entirety of the models. The total deformation and equivalent stress of the proximal femur were recorded before and after the removal of internal fixation. RESULTS: Under the standing condition, the total deformation of the model before and after removing CSS was 0.99 mm and 1.10 mm, respectively, indicating an increase of 12%. The total deformation of the model before and after removing FNS was 0.65 mm and 0.76 mm, respectively, indicating an increase of 17%. The equivalent stress for CSS and FNS were 55.21 MPa and 250.67 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of CSS was 7.76 MPa and 6.11 MPa, respectively. The average equivalent stress on the cross-section of the femoral neck before and after removal of FNS was 9.89 MPa and 8.79 MPa, respectively. CONCLUSIONS: The retention of internal fixation may contribute to improved stability of the proximal femur. However, there still existed risks of stress concentration in internal fixation and stress shielding in the proximal femur. Compared to CSS, the removal of FNS results in larger bone tunnels and insufficient model stability. Further clinical interventions are recommended to address this issue.

Bond performance between hybrid fiber-reinforced concrete and BFRP bars under freeze-thaw cycle.

This study applied the pull-out test to examine the influence of freeze-thaw cycles and hybrid fiber incorporation on the bond performance between BFRP bars and hybrid fiber-reinforced concrete. The bond-slip curves were fitted by the existing bond-slip constitutive model, and then the bond strength was predicted by a BP neural network. The results indicated that the failure mode changed from pull-out to splitting for the BFRP bar ordinary concrete specimens when the freeze-thaw cycles exceeded 50, while only pull-out failure occurred for all BFRP bar hybrid fiber-reinforced concrete specimens. An increasing trend was shown on the peak slip, but a decreasing trend was shown on the bond stiffness and bond strength when freeze-thaw cycles increased. The bond strength could be increased significantly by the incorporation of basalt fiber (BF) and cellulose fiber (CF) under the same freezing and thawing conditions as compared to concrete specimens without fibers. The Malvar model and the Continuous Curve model performed best in fitting the ascending and descending sections of the bond-slip curves, respectively. The BP neural network also accurately predicted the bond strength, with relative errors of predicted bond strengths ranging from 3.75% to 13.7%, and 86% of them being less than 10%.

Effects of various load magnitudes on ACL: an in vitro study using adolescent porcine stifle joints.

INTRODUCTION: The escalating incidence of anterior cruciate ligament (ACL) injuries, particularly among adolescents, is a pressing concern. The study of ACL biomechanics in this demographic presents challenges due to the scarcity of cadaveric specimens. This research endeavors to validate the adolescent porcine stifle joint as a fitting model for ACL studies. METHODS: We conducted experiments on 30 fresh porcine stifle knee joints. (Breed: Yorkshire, Weight: avg 90 lbs, Age Range: 2-4 months). They were stored at - 22 °C and a subsequent 24-h thaw at room temperature before being prepared for the experiment. These joints were randomly assigned to three groups. The first group served as a control and underwent only the load-to-failure test. The remaining two groups were subjected to 100 cycles, with forces of 300N and 520N, respectively. The load values of 300N and 520N correspond to three and five times the body weight (BW) of our juvenile porcine, respectively. RESULT: The 520N force demonstrated a higher strain than the 300N, indicating a direct correlation between ACL strain and augmented loads. A significant difference in load-to-failure (p = 0.014) was observed between non-cyclically loaded ACLs and those subjected to 100 cycles at 520N. Three of the ten samples in the 520N group failed before completing 100 cycles. The ruptured ACLs from these tests closely resembled adolescent ACL injuries in detachment patterns. ACL stiffness was also measured post-cyclical loading by applying force and pulling the ACL at a rate of 1 mm per sec. Moreover, ACL stiffness measurements decreased from 152.46 N/mm in the control group to 129.42 N/mm after 100 cycles at 300N and a more significant drop to 86.90 N/mm after 100 cycles at 520N. A one-way analysis of variance (ANOVA) and t-test were chosen for statistical analysis. CONCLUSIONS: The porcine stifle joint is an appropriate model for understanding ACL biomechanics in the skeletally immature demographic. The results emphasize the ligament's susceptibility to injury under high-impact loads pertinent to sports activities. The study advocates for further research into different loading scenarios and the protective role of muscle co-activation in ACL injury prevention.

Understanding osteokine biology.

Bone is an endocrine organ that participates in whole-body homeostasis. The biology of bone-derived osteokines, however, remains unclear. Liang et al. integrate experimental and computational methods to discover new osteokines, establish their cell of origin and target site, and study their role in aging and during mechanical stress.

Finite element analysis of kangaroo astragali: A new angle on the ankle.

Using finite element analysis on the astragali of five macropodine kangaroos (extant and extinct hoppers) and three sthenurine kangaroos (extinct proposed bipedal striders) we investigate how the stresses experienced by the ankle in similarly sized kangaroos of different hypothesized/known locomotor strategy compare under different simulation scenarios, intended to represent the moment of midstance at different gaits. These tests showed a clear difference between the performance of sthenurines and macropodines with the former group experiencing lower stress in simulated bipedal strides in all species compared with hopping simulations, supporting the hypothesis that sthenurines may have utilized this gait. The Pleistocene macropodine Protemnodon also performed differently from all other species studied, showing high stresses in all simulations except for bounding. This may support the hypothesis of Protemnodon being a quadrupedal bounder.

Short-range correlation of stress chains near solid-to-liquid transition in active monolayers.

Using a three-dimensional model of cell monolayers, we study the spatial organization of active stress chains as the monolayer transitions from a solid to a liquid state. The critical exponents that characterize this transition map the isotropic stress percolation onto the two-dimensional random percolation universality class, suggesting short-range stress correlations near this transition. This mapping is achieved via two distinct, independent pathways: (i) cell-cell adhesion and (ii) active traction forces. We unify our findings by linking the nature of this transition to high-stress fluctuations, distinctly linked to each pathway. The results elevate the importance of the transmission of mechanical information in dense active matter and provide a new context for understanding the non-equilibrium statistical physics of phase transition in active systems.

Effects of hexagonal boron nitride on mechanical properties of bone cement (Polymethylmethacrylate).

OBJECTIVES: The aim of this study was to investigate the effects of adding hexagonal boron nitride at four different concentrations to polymethylmethacrylate (PMMA) bone cement, which is commonly used in orthopedic surgeries, on the mechanical properties and microarchitecture of the bone cement. MATERIALS AND METHODS: The study included an unaltered control group and groups containing four different concentrations (40 g of bone cement with 0.5 g, 1 g, 1.5 g, 2 g) of hexagonal boron nitride. The samples used for mechanical tests were prepared at 20±2ºC in operating room conditions, using molds in accordance with the test standards. As a result of the tests, the pressure values at which the samples deformed were determined from the load-deformation graphs, and the megapascal (MPa) values at which the samples exhibited strength were calculated. RESULTS: The samples with 0.5 g boron added to the bone cement had significantly increased mechanical strength, particularly in the compression test. In the group where 2 g boron was added, it was noted that, compared to the other groups, the strength pressure decreased and the porosity increased. The porosity did not change particularly in the group where 0.5 g boron was added. CONCLUSION: Our study results demonstrate that adding hexagonal boron nitride (HBN) to bone cement at a low concentration (0.5 g / 40 g PPMA) significantly increases the mechanical strength in terms of MPa (compression forces) without adversely affecting porosity. However, the incorporation of HBN at higher concentrations increases porosity, thereby compromising the biomechanical properties of the bone cement, as evidenced by the negative impact on compression and four-point bending tests. Boron-based products have gained increased utilization in the medical field, and HBN is emerging as a promising chemical compound, steadily growing in significance.

Mechanically strained osteocyte-derived exosomes contained miR-3110-5p and miR-3058-3p and promoted osteoblastic differentiation.

BACKGROUND: Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important. RESULTS: A mechanical tensile strain of 2500 µÎµ at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR). CONCLUSIONS: In osteocytes, a mechanical tensile strain of 2500 µÎµ at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.

Actomyosin-II protects axons from degeneration induced by mild mechanical stress.

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.