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Hormonal changes during lactation are associated with profound changes in bone cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger lacuna shape theoretically enhances the transmission of mechanical signals to osteocytes. We aimed to provide experimental evidence supporting this theory by comparing the mechanoresponse of osteocytes in the bone of lactating mice, which have enlarged lacunae due to osteocytic osteolysis, with the response of osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse was measured in excised fibulae that were cultured in hormone-free medium for 24 h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 µε, 5 Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and sclerostin and β-catenin protein expression (immunohistochemistry). Loading decreased Sost expression by ~ threefold in fibulae of lactating mice. The loading-induced decrease in sclerostin protein expression by osteocytes was larger in lactating mice (55% decrease ± 14 (± SD), n = 8) than virgin mice (33% decrease ± 15, n = 7). Mechanical loading upregulated β-catenin expression in osteocytes in lactating mice by 3.5-fold (± 0.2, n = 6) which is significantly (p < 0.01) higher than the 1.6-fold increase in β-catenin expression by osteocytes in fibulae from virgin mice (± 0.12, n = 4). These results suggest that osteocytes in fibulae from lactating mice with large lacunae may respond stronger to mechanical loading than those from virgin mice. This could indicate that osteocytes residing in larger lacuna show a stronger response to mechanical loading.

Safe Underground Gas Storage (UGS) can be achieved in artificial, salt caverns to meet fluctuations in energy demand by providing adequate knowledge on rock salt when subjected to similar cyclic conditions. In this study, we performed cyclic mechanical tests on five rock salt samples with different types and amounts of second-phase mineral content. A confining pressure of 25 MPa was applied, whilst the axial stress was cycled between 4.5 and 7.5 MPa, at 0.5 kN/s loading rate, during 48 h (7200 cycles). The results demonstrate that high second-phase content such as anhydrite layering operates as a strength weakening agent by accommodating larger brittle deformation in comparison to samples with a lower content in secondary minerals. This rheological behavior is further exacerbated by the cycling mechanical conditions and recorded by a marked step on Young’s modulus and Poisson’s ratio value evolution. The microstructure analysis reveals how halite grains accommodate most of the deformation induced by the cyclic mechanical loading conditions through brittle deformation with microfracturing network development. Other structures from different deformation mechanisms are also discussed. Two types of new porosity are observed: (i) pores around isolated crystals of second-phase minerals as a result of grain rotation under cyclic mechanical deformation, and (ii) microcracks in areas with high concentration of secondary minerals (such as anhydrite, polyhalite, carnallite, or kieserite). This porosity change has strong implications for both the mechanical behavior of the material and its potential permeability.

Pressure ulcers are localized sites of tissue damage which form due to the continuous exposure of skin and underlying soft tissues to sustained mechanical loading, by bodyweight forces or because a body site is in prolonged contact with an interfacing object. The latter is the common cause for the specific sub-class of pressure ulcers termed ‘medical device-related pressure ulcers’, where the injury is known to have been caused by a medical device applied for a diagnostic or therapeutic purpose. Etiological research has established three key contributors to pressure ulcer formation, namely direct cell and tissue deformation, inflammatory edema and ischemic damage which are typically activated sequentially to fuel the injury spiral. Here, we visualize and analyze the above etiological mechanism using a new cell-scale modeling framework. Specifically, we consider here the deformation-inflicted and inflammatory contributors to the damage progression in a medical device-related pressure ulcer scenario, forming under a continuous positive airway pressure ventilation mask at the microarchitecture of the nasal bridge. We demonstrate the detrimental effects of exposure to high-level continuous external strains, which causes deformation-inflicted cell damage almost immediately. This in turn induces localized edema, which exacerbates the cell-scale mechanical loading state and thereby progresses cell damage further in a nonlinear, escalating pattern. The cell-scale quantitative description of the damage cascade provided here is important not only from a basic science perspective, but also for creating awareness among clinicians as well as industry and regulators with regards to the need for improving the design of skin-contacting medical devices.

Resolution of inflammation is essential for normal tissue healing and regeneration, with macrophages playing a key role in regulating this process through phenotypic changes from a pro-inflammatory to an anti-inflammatory state. Pharmacological and mechanical (mechanotherapy) techniques can be employed to polarize macrophages toward an anti-inflammatory phenotype, thereby diminishing inflammation. One clinically relevant pharmacological approach is the inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). This study investigates the effects of various mechanical loading amplitudes (0%, 3%, and 6%) and TRPV4 inhibition (10 µM RN-1734) on the phenotypic commitments of pro-inflammatory (M1) macrophages within three-dimensional (3D) collagen matrices. M1 macrophages exposed to 3% mechanical strain exhibited upregulated pro-inflammatory responses, including increased pro-inflammatory gene expression and enhanced proteolytic activity within the extracellular matrix. TRPV4 inhibition partially mitigated this inflammation. Notably, 6% mechanical strain combined with TRPV4 inhibition suppressed Mitogen-Activated Protein Kinase (MAPK) expression, leading to reduced pro-inflammatory gene expression and increased anti-inflammatory markers such as CD206. Gene expression analysis further demonstrated significant reductions in pro-inflammatory gene expression and a synergistic promotion of anti-inflammatory phenotypes under TRPV4 inhibition at 6% mechanical strain. Surface protein analysis via immunohistochemistry confirmed these phenotypic shifts, highlighting changes in the expression of CD80 (pro-inflammatory) and CD206 (anti-inflammatory) markers, alongside F-actin and nuclear staining. This research suggests that TRPV4 inhibition, combined with specific mechanical loading (6%), can drive macrophages toward an anti-inflammatory state, thereby may promote inflammation resolution and tissue repair.

Background The porous structure in bone tissue is essential for maintaining the physiological functions and overall health of intraosseous cells. The lacunar-canalicular net (LCN), a microscopic porous structure within osteons, facilitates the transport of nutrients and signaling molecules through interstitial fluid flow. However, the transient behavior of fluid flow within these micro-pores under dynamic loading conditions remains insufficiently studied. Methods The study constructs a fluid-solid coupling model including the Haversian canal, canaliculi, lacunae, and interstitial fluid, to examine interstitial fluid flow behavior within the LCN under dynamic loading with varying frequencies and amplitudes. The relationship between changes of LCN pore volume and fluid velocity, and pressure is researched. Results The results demonstrate that increasing strain amplitude leads to significant changes of LCN pore volume within osteons. In a complete loading cycle, with the increase of compressive strain, the pore volume in the osteon gradually shrinks, and the pressure gradient in the LCN increases, which promotes the increase of interstitial fluid velocity. When the compressive strain reaches the peak value, the flow velocity also reaches the maximum. In the subsequent unloading process, the pore volume began to recover, the pressure gradient gradually decreased, the flow rate decreased accordingly, and finally returned to the steady state level. At a loading amplitude of 1000 µε, the pore volume within LCN decreases by 1.1‰. At load amplitudes of 1500 µε, 2000 µε, and 2500 µε, the pore volume decreases by 1.6‰, 2.2‰ and 2.7‰ respectively, and the average flow velocity at the center of the superficial lacuna is 1.36 times, 1.77 times, and 2.14 times that at 1000 µε, respectively. Additionally, at a loading amplitude of 1000 µε under three different loading frequencies, the average flow velocities at the center of the superficial bone lacuna are 0.60 μm/s, 1.04 μm/s, and 1.54 μm/s, respectively. This indicates that high-frequency and high-amplitude dynamic loading can promote more vigorous fluid flow and pressure fluctuations with changes in LCN pore volume. Conclusions Dynamic mechanical loading can significantly enhance the interstitial fluid flow in LCN by the changes of LCN pore volume. and dynamic loading promoted fluid flow in shallow lacunae significantly higher than that in deep lacunae. The relationship between changes of LCN pore volume and interstitial fluid flow behavior has implications for drug delivery and bone tissue engineering research.

Creep deformation in shale rocks is an important factor in many applications, such as the sustainability of geostructures, wellbore stability, evaluation of land subsidence, CO2 storage, toxic waste containment, and hydraulic fracturing. One mechanism leading to this time-dependent deformation under a constant load is the dissolution/formation processes accompanied by chemo-mechanical interactions with a reactive environment. When dissolution/formation processes occur within the material phases, the distribution of stress and strain within the material microstructure changes. In the case of the dissolution process, the stress carried by the dissolving phase is distributed into neighboring voxels, which leads to further deformation of the material. The aim of this study was to explore the relationship between the microstructural evolution and time-dependent creep behavior of rocks subjected to chemo-mechanical loading. This work uses the experimentally characterized microstructural and mechanical evolution of a shale rock induced by interactions with a reactive brine (CO2-rich brine) and a non-reactive brine (N2-rich brine) under high-pressure and high-temperature conditions to compute the resulting time-dependent deformation using a time-stepping finite-element-based modeling approach. Sample microstructure snapshots were obtained using segmented micro-CT images of the rock samples before and after the reactions. Coupled nanoindentation/EDS provided spatial alteration of the mechanical properties of individual material phases due to the dissolution and precipitation processes as a result of chemo-mechanical loading of the samples. The time-dependent mechanically informed microstructures were then incorporated into a mechanical model to calculate the creep behavior caused by the dissolution/precipitation processes independent of the inherent viscous properties of the mineral phases. The results indicate the substantial role of the dissolution/precipitation processes on the viscous behavior of rocks subjected to reactive environments.HighlightsA computational scheme incorporating experimental data calculated time-dependent creep strain in shale rock due to chemo-mechanical loading.A time-dependent microstructural model and time-stepping finite element model were coupled to build the computational framework.Micro-CT imaging and coupled nanoidentation/EDS techniques were utilized in the microstructural model to study the evolution of shale rock exposed to CO2- and N2-rich brine, at high-pressure and high-temperature conditions.Creep deformation distribution varied based on the extent and spatial variability of the reaction, with different behavior observed under CO2 and N2 conditions.The results highlight the important role of the interplay between the dissolution and precipitation processes on the VE/VP behavior of rocks in reactive environments.

Abstract A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous. In addition, TRPV4 is involved in bone development. Therefore, this study aims to construct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical environment on the osteogenic differentiation of stem cells and bone repair in vivo. The role of TRPV4 in the mechanobiology process was also assessed. A sodium alginate–gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained. The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%. TRPV4 was activated in the hydrogel with fast stress relaxation time, followed by the increase in intracellular Ca2+ level and the activation of the Wnt/β-catenin pathway. The inhibition of TRPV4 induced a decrease in the intracellular Ca2+ level, down-regulation of β-catenin and reduced osteogenesis differentiation of BMSCs, suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment. The fast stress relaxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model. The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration, which TRPV4 being involved in this mechanobiological process. Our study not only provided important guidance for the mechanical design of new biomaterials, but also provided a new perspective for the understanding of the interaction between cells and materials, the role of mechanical loading in tissue regeneration and the use of mechanical regulation in tissue engineering. Graphical Abstract

A high‐temperature multi‐axial test is carried out to characterize the thermo‐mechanical behaviour of a 3D‐woven SiC/SiC composite aeronautical part under loads representative of operating conditions. The sample is L‐shaped and cut out from the part. It is subjected to severe thermal gradients and a superimposed mechanical load that progressively increases up to the first damage. The sample shape and its associated microstructure, the heterogeneity of the stress field and the limited accessibility to regions susceptible to damage require non‐contact imaging modalities. An in situ experiment, conducted with a dedicated testing machine at the SOLEIL synchrotron facility, provides the sample microstructure from computed micro‐tomographic imaging and thermal loads from infrared thermography. Experimental constraints lead to non‐ideal acquisition conditions for both measurement modalities. This article details the procedure of correcting artefacts to use the volumes for quantitative exploitation (i.e. full‐field measurement, model validation and identification). After proper processing, despite its complexity, the in situ experiment provides high‐quality data about a part under realistic operating conditions. The influence of the mesostructure on fracture phenomena can be inferred from the tomography in the damaged state. Experiments show that the localization of damage initiation is driven by the geometry, while the woven structure moderates the crack propagation. This study widens the scope of in situ thermo‐mechanical experiments to more complex loading states, closer to in‐service conditions. An in situ corner bending test under a high thermal gradient is followed by both computed tomography and thermography. Experimental procedure, image processing and preliminary conclusion are presented.

In this study, effects of combining optimized tissue engineering bone (TEB) implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits were investigated. Physiological characteristics of bone marrow mesenchymal stem cells (BMMSCs), compact bone cells (CBCs), and bone marrow and compact bone coculture cells (BMMSC-CBCs) were compared to select the optimal seed cells for optimized TEB construction. Rabbits with segmental bone defects were treated in different ways (cancellous bone scaffold for group A, cancellous bone scaffold and mechanical loading for group B, optimized TEB for group C, optimized TEB and mechanical loading for group D, n = 4), and the bone repair were compared. BMMSC-CBCs showed better proliferation capacity than CBCs (p < 0.01) and stronger osteogenic differentiation ability than BMMSCs (p < 0.05). Heel-strike like mechanical loading improved proliferation and osteogenic differentiation ability and expression levels of TGFβ1 as well as BMP2 of seed cells in vitro (p < 0.05). At week 12 post-operation, group D showed the best bone repair, followed by groups B and C, while group A finished last (p < 0.05). During week 4 to 12 post-operation, group D peaked in terms of expression levels of TGFβ1, BMP2, and OCN, followed by groups B and C, while group A finished last (p < 0.05). Thus, BMMSC-CBCs showed good proliferation and osteogenic differentiation ability, and they were thought to be better as seed cells than BMMSCs and CBCs. The optimized TEB implantation combined with heel-strike like mechanical loading had a synergistic effect on bone defect healing, and enhanced expression of TGFβ1 and BMP2 played an important role in this process.

Purpose The present research aimed to assess the impact of endodontic access cavity preparation on the fracture resistance of CAD-CAM crowns. Materials and methods A total of 40 extracted human upper first premolars were utilized in present research. All premolars were affixed in epoxy resin blocks, prepared by utilizing a CNC milling machine to receive full coverage ceramic crowns, and evenly split into two primary groups based on the type of ceramic; Group LD: teeth restored with lithium-disilicate (LD) crowns, and Group PIC: teeth restored with polymer-infiltrated ceramic (PIC) crowns. Every group was subdivided into 2 subgroups ( n =10); Subgroup LDI: Intact LD crowns, Subgroup LDR: Repaired LD crowns, Subgroup PICI: Intact vita PIC crowns, and Subgroup PICR: Repaired PIC crowns. Crowns were cemented using Calibra Universal resin cement. The repaired subgroups received a standardized access cavity at the center of the occlusal surface and then repaired with direct composite resin. All samples were exposed to thermo-mechanical loading in a chewing simulator for 118,000 cycles, loaded until failure, and then statistically analyzed. Results For intact control subgroups, the greatest mean scores were showed in PICI (1308.71±244.15 N) compared to LDI (1154.38±133.83 N), and the variation was not statistically significant ( P =0.097). For repaired subgroups, the highest mean values were recorded for PICR (727.84±240.52 N) compared to LDR (707.03±298.28 N), and the variation was not statistically significant ( P =0.866). Conclusions Both LD and PIC crowns perform the same after exposure to an endodontic access cavity, suggesting their repairability and useability.