Search

Cells can sense and respond to different kinds of continuous mechanical strain in the human body. Mechanical stimulation needs to be included within the in vitro culture system to better mimic the existing complexity of in vivo biological systems. Existing commercial dynamic culture systems are generally two-dimensional (2D) which fail to mimic the three-dimensional (3D) native microenvironment. In this study, a pneumatically driven fiber robot has been developed as a platform for 3D dynamic cell culture. The fiber robot can generate tunable contractions upon stimulation. The surface of the fiber robot is formed by a braiding structure, which provides promising surface contact and adequate space for cell culture. An in-house dynamic stimulation using the fiber robot was set up to maintain NIH3T3 cells in a controlled environment. The biocompatibility of the developed dynamic culture systems was analyzed using LIVE/DEAD™ and alamarBlue™ assays. The results showed that the dynamic culture system was able to support cell proliferation with minimal cytotoxicity similar to static cultures. However, we observed a decrease in cell viability in the case of a high strain rate in dynamic cultures. Differences in cell arrangement and proliferation were observed between braided sleeves made of different materials (nylon and ultra-high molecular weight polyethylene). In summary, a simple and cost-effective 3D dynamic culture system has been proposed, which can be easily implemented to study complex biological phenomena in vitro.

To estimate the multiaxial notch local elastic–plastic strains real timely, an online notch elastic–plastic analytical method is proposed coupling with the modified pseudo stress criterion and Chaboche constitutive model. Moreover, for the Ramberg–Osgood material, the non-proportional cyclic strain hardening can be well considered by the proposed unified online accumulation method of equivalent plastic strain increment. Meanwhile, a rapid and effective simulating algorithm for the proposed online method is provided and verified by the experimental data of TC21 titanium alloy and SAE1070 steel notched specimens. Comparisons show that the simulated results can agree with the measured data quite well under multiaxial irregular loading.

The delocalized exciton on conjugated polymers plays a momentous role in efficient charge generation and transport processes. Because the exciton is delocalized over the conjugated backbone, the ex...

The present paper aims to show the ability of the extended overstress subloading surface EOSS theory to model the rate-dependency of metallic materials subjected to different loading conditions. The numerical results were carried out by means of Finite Elements FE simulations reproducing pure creep, stress relaxation, monotonic tensile and cyclic loading conditions. A particular emphasis is given to show the model response under quasi-static and high strain rates loading conditions describing the evolution of the main variables and investigating the convergence rate of the implicit integration scheme. The validation of the EOSS model is carried out against experimental tests, found in the literature, on a lead-free solder material and a SS316L stainless steel. The numerical results are in good agreement with the experimental data proving the ability of the EOSS model to catch a realistic material description.

Plastic deformations of metallic materials depend on the rate of loading or deformation, implying rate-independent constitutive theories cannot catch a realistic response of the material when the loading condition is not quasi-static. Considering the conventional rate-dependent algorithms, the description of irreversible deformations does not show a smooth transition of the so-called viscoplastic strain from the elastic domain to the viscoplastic domain. In fact, a sudden generation of irreversible deformation takes place whenever the stress state exceeds the macroscopic yield stress during loading. Moreover, some models that adopt the overstress concept are not suitable for the description of impact loadings, since they predict an unrealistic elastic response, implying that the material could bear an infinite load. The present paper adopted the overstress subloading surface theory, which overcame the previous drawbacks. The constitutive equations were modified to take into account the movement of the similarity centre with the viscoplastic deformations to extend the description of the rate-dependency of the material to cyclic loading conditions. Moreover, aspects of the finite step accuracy of the algorithm and the local convergence are discussed.

Background The non-uniform distribution of atherosclerosis within the arterial system is widely attributed to variation in haemodynamic wall shear stress. It may also depend on variation in pressure-induced stresses and strains within the arterial wall; these have been less widely investigated, at least in part because of a lack of suitable techniques. Objectives Here we show that local arterial strain can be determined from impressions left by endothelial cells on the surface of vascular corrosion casts made at different pressures, even though only one pressure can be examined in each vessel. The pattern of pits in the cast caused by protruding endothelial nuclei was subject to “retro-deformation” to identify the pattern that would have occurred in the absence of applied stresses. Methods Retaining the nearest-neighbour pairs found under this condition, changes in nearest-neighbour vectors were calculated for the pattern seen in the cast, and the ratio of mean changes at different pressures determined. This approach removes errors in simple nearest-neighbour analyses caused by the nearest neighbour changing as deformation occurs. Results The accuracy, precision and robustness of the approach were validated using simulations. The method was implemented using confocal microscopy of casts of the rabbit aorta made at systolic and diastolic pressures; results agreed well with the ratio of the macroscopic dimensions of the casts. Conclusions Applying the new technique to areas around arterial branches could support or refute the hypothesis that the development of atherosclerosis is influenced by mural strain, and the method may be applicable to other tissues.

Different grain coarsening behaviors (i.e. abnormal and homogeneous) are prevalently observed in gradient nanograined (GNG) Cu under stress controlled high-cycle and strain controlled low-cycle fatigue tests, respectively. In this paper, to comprehensively understand the intrinsic fatigue mechanism of gradient nanograined structures, both high and low cycle fatigue behaviors of GNG Cu are investigated under strain-controlled fatigue tests with a wide strain amplitude ranges. Cyclic behavior transition from abnormal grain coarsening at small strain amplitude to homogeneous grain coarsening at large strain amplitude is observd in GNG Cu. Microstrucural analysis reveals that the grain coarsening behavior in either abnormal or normal (homogeneous) mode is closely related to the spatial distribution of the cyclic plastic strain in the GNG layer (localized or delocalized) under cyclic loading. Such unique cyclic strain amplitude-dependent fatigue behavior is inherent to the gradient nanostructure, which fundamentally differs from the conventional strain localizing mechanism in metals with homogeneous structures under cyclic loading.

The influence of stress rate ( σ ˙ ) on load/strain partitioning between different phases of a micro-alloyed 2.25Cr–Mo steel during stress-controlled fatigue deformation at room temperature (RT) wa...

Healing after tooth extraction involves a series of reparative processes affecting both alveolar bone and soft tissues. The aim of the present study was to investigate whether activation of molecular signals during the healing process confers a regenerative advantage to the extraction socket soft tissue (ESsT) at 8 weeks of healing. Compared to subepithelial connective tissue graft (CTG), qRT-PCR analyses revealed a dramatic enrichment of the ESsT in osteogenic differentiation markers. However, ESsT and CTG shared characteristics of nonspecialized soft connective tissue by expressing comparable levels of genes encoding abundant extracellular matrix (ECM) proteins. Genes encoding the transforming growth factor-β1 (TGF-β1) and its receptors were strongly enriched in the CTG, whereas the transcript for the insulin-like growth factor-1 (IGF-1) showed significantly high and comparable expression in both tissues. Mechanical stimulation, by the means of cyclic strain or matrix stiffness applied to primary ESsT cells (ESsT-C) and CTG fibroblasts (CTG-F) extracted from the tissue samples, revealed that stress-induced TGF-β1 not exceeding 2.3 ng/mL, as measured by ELISA, in combination with IGF-1 up to 2.5 ng/mL was able to induce the osteogenic potential of ESsT-Cs. However, stiff matrices (50 kPa), upregulating the TGF-β1 expression up to 6.6 ng/mL, caused downregulation of osteogenic gene expression in the ESsT-Cs. In CTG-Fs, endogenous or stress-induced TGF-β1 ≥ 4.6 ng/mL was likely responsible for the complete lack of osteogenesis. Treatment of ESsT-Cs with TGF-β1 and IGF-1 proved that, at specific concentrations, the two growth factors exhibited either an inductive-synergistic or a suppressive activity, thus determining the osteogenic and mineralization potential of ESsT-Cs. Taken together, our data strongly warrant the clinical exploration of ESsT as a graft in augmentative procedures during dental implant placement surgeries.

The heart has a dynamic mechanical environment contributed by its unique cellular composition and the resultant complex tissue structure. In pathological heart tissue, both the mechanics and cell composition can change and influence each other. As a result, the interplay between the cell phenotype and mechanical stimulation needs to be considered to understand the biophysical cell interactions and organization in healthy and diseased myocardium. In this work, we hypothesized that the overall tissue organization is controlled by varying densities of cardiomyocytes and fibroblasts in the heart. In order to test this hypothesis, we utilized a combination of mechanical strain, co-cultures of different cell types, and inhibitory drugs that block intercellular junction formation. To accomplish this, an image analysis pipeline was developed to automatically measure cell type-specific organization relative to the stretch direction. The results indicated that cardiac cell type-specific densities influence the overall organization of heart tissue such that it is possible to model healthy and fibrotic heart tissue in vitro. This study provides insight into how to mimic the dynamic mechanical environment of the heart in engineered tissue as well as providing valuable information about the process of cardiac remodeling and repair in diseased hearts.

The neural stem cell (NSC) niche is a highly vascularized microenvironment that supplies stem cells with relevant biological and chemical cues. However, the NSCs’ proximity to the vasculature also means that the NSCs are subjected to permanent tissue deformation effected by the vessels’ heartbeat-induced pulsatile movements. Cultivating NSCs under common culture conditions neglects the—yet unknown—influence of this cyclic mechanical strain on neural stem cells. Under the hypothesis that pulsatile strain should affect essential NSC functions, a cyclic uniaxial strain was applied under biomimetic conditions using an in-house developed stretching system based on cross-linked polydimethylsiloxane (PDMS) elastomer. While lineage commitment remained unaffected by cyclic deformation, strain affected NSC quiescence and cytoskeletal organization. Unexpectedly, cyclically stretched stem cells aligned in stretch direction, a phenomenon unknown for other types of cells in the mammalian organism. The same effect was observed for young astrocytes differentiating from NSCs. In contrast, young neurons differentiating from NSCs did not show mechanoresponsiveness. The exceptional orientation of NSCs and young astrocytes in the stretch direction was blocked upon RhoA activation and went along with a lack of stress fibers. Compared to postnatal astrocytes and mature neurons, NSCs and their young progeny displayed characteristic and distinct mechanoresponsiveness. Data suggest a protective role of young astrocytes in mixed cultures of differentiating neurons and astrocytes by mitigating the mechanical stress of pulsatile strain on developing neurons.

Soft organisms such as earthworms can access confined, narrow spaces, inspiring scientists to fabricate soft robots for in vivo manipulation of cells or tissues and minimally invasive surgery. We report a super-soft and super-elastic magnetic DNA hydrogel-based soft robot (DNA robot), which presents a shape-adaptive property and enables magnetically driven navigational locomotion in confined and unstructured space. The DNA hydrogel is designed with a combinational dynamic and permanent crosslinking network through chain entanglement and DNA hybridization, resulting in shear-thinning and cyclic strain properties. DNA robot completes a series of complex magnetically driven navigational locomotion such as passing through narrow channels and pipes, entering grooves and itinerating in a maze by adapting and recovering its shape. DNA robot successfully works as a vehicle to deliver cells in confined space by virtue of the 3D porous networked structure and great biocompatibility.

Controlling macrophage behavior has become a high-potential target strategy for regenerative therapies, such as in situ tissue engineering (TE). In situ TE is an approach, in which acellular resorbable synthetic scaffolds are used, to induce endogenous tissue regeneration. However, little is known regarding the effect of the biomechanical environment on the macrophage response to a scaffold. Therefore, the aim of this study was to assess the effect of cyclic strains (0%, 8%, and 14% strain) on primary human macrophage polarization in electrospun scaffolds with two different fiber diameters in the micrometer range (4 μm or 13 μm). High strains led to a proinflammatory profile in terms of gene expression, expression of surface proteins, and cytokine secretion. These results were consistent for scaffolds with small and large fiber diameters, indicating that the effect of cyclic strain was not affected by the different scaffold microstructures. Notably, macrophages were identified as direct contributors of early secretion of extracellular matrix proteins, including elastin, which was deposited in a strain-dependent manner. These findings are instrumental for the rational design of scaffolds for in situ TE and underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, for example, in terms of stiffness and compliance, to support a desirable proregenerative macrophage phenotype. Electrospun elastomeric scaffolds are being used for a variety of in situ tissue engineering applications, in which biomechanical loads play a dominant in vivo role, such as cardiovascular replacements (e.g., heart valve and blood vessel prostheses) and pelvic floor reconstruction. The findings of this study underline that immunomodulatory scaffolds for biomechanically loaded applications should be mechanically tailored, for example, in terms of stiffness and compliance, to support a desirable proregenerative macrophage phenotype. Moreover, this research contributes to the general understanding of pathophysiological macrophage phenotypes in cyclically strained tissues (e.g., atherosclerotic plaques), and their role in tissue regeneration and degeneration.

Formation of a barrier capable of protecting tissue from external damage, chemical factors, and pathogens is one of the main functions of the epidermis. Furthermore, upon development and during aging, mechanoprotective epidermal functions change dramatically. However, comparative studies between embryonic and adult skin in comparison to skin equivalents are still scarce which is especially due to the lack of appropriate measurement systems with sufficient accuracy and long-term tissue compatibility. Our studies fill this gap by developing a combined bioreactor and tensile testing machine for biomechanical analysis of living epithelia. Based on this tissue stretcher, our data clearly show that viscoelastic and plastic deformation behavior of embryonic and adult skin differ significantly. Tissue responses to static strain compared to cyclic strain also show a clear dependence on differentiation stage. Multilayered unkeratinized epidermis equivalents, on the other hand, respond very similar to mechanical stretch as adult tissue. This mechanical similarity is even more evident after a single cycle of mechanical preconditioning. Our studies therefore suggest that skin equivalents are well suited model systems to analyze cellular interactions of epidermal cells in natural tissues.

This paper investigated the application of the cyclic strain approach to the analysis of ocean wave liquefaction. The threshold shear strain concept was conceived in the early 1980s for the...

Overuse tendon injuries are a major cause of musculoskeletal morbidity in both human and equine athletes, due to the cumulative degenerative damage. These injuries present significant challenges as the healing process often results in the formation of inferior scar tissue. The poor success with conventional therapy supports the need to search for novel treatments to restore functionality and regenerate tissue as close to native tendon as possible. Mesenchymal stem cell (MSC)-based strategies represent promising therapeutic tools for tendon repair in both human and veterinary medicine. The translation of tissue engineering strategies from basic research findings, however, into clinical use has been hampered by the limited understanding of the multifaceted MSC mechanisms of action. In vitro models serve as important biological tools to study cell behavior, bypassing the confounding factors associated with in vivo experiments. Controllable and reproducible in vitro conditions should be provided to study the MSC healing mechanisms in tendon injuries. Unfortunately, no physiologically representative tendinopathy models exist to date. A major shortcoming of most currently available in vitro tendon models is the lack of extracellular tendon matrix and vascular supply. These models often make use of synthetic biomaterials, which do not reflect the natural tendon composition. Alternatively, decellularized tendon has been applied, but it is challenging to obtain reproducible results due to its variable composition, less efficient cell seeding approaches and lack of cell encapsulation and vascularization. The current review will overview pros and cons associated with the use of different biomaterials and technologies enabling scaffold production. In addition, the characteristics of the ideal, state-of-the-art tendinopathy model will be discussed. Briefly, a representative in vitro tendinopathy model should be vascularized and mimic the hierarchical structure of the tendon matrix with elongated cells being organized in a parallel fashion and subjected to uniaxial stretching. Incorporation of mechanical stimulation, preferably uniaxial stretching may be a key element in order to obtain appropriate matrix alignment and create a pathophysiological model. Together, a thorough discussion on the current status and future directions for tendon models will enhance fundamental MSC research, accelerating translation of MSC therapies for tendon injuries from bench to bedside.

With increasing vehicular traffic on the roads, the production of rubber is steeply increased over the years. Consequently, more and more scrapped rubber tires are discarded every year, and most of them are ended up in municipal landfills. As a remedy to this, researchers are trying to use these wastes in better ways, such as filling material in earthen embankments, rather than letting them get dumped in landfills. This study aims to investigate the effect of dynamic loads on the performance of rubber tire chips, a scrap tire derivative, in its saturated state. For the study, a series of strain-controlled cyclic triaxial tests were performed. The parameters like cyclic strain amplitude (0.075, 0.1125, 0.15, 0.1875, 0.225, 0.2625, and 0.3%) and confining pressure (50, 75, and 100 kPa) were selected as variables. The rubber tire chips with average dimension of 12 mm x 20 mm were considered for the study. The dynamic properties obtained are compared with that of the Indian standard sand. The number of loading cycles for initiation of liquefaction is used to compare the liquefaction potential of the rubber tire chips with that of the standard sand. The cyclic tests showed that the tire chips do not liquefy for large number of loading cycles. The tire chips showed very high damping ratios in comparison with sand but are considerably low in their shear modulus.

The most advanced in vitro cardiac models are today based on the use of induced pluripotent stem cells (iPSCs); however, the maturation of cardiomyocytes (CMs) has not yet been fully achieved. Therefore, there is a rising need to move towards models capable of promoting an adult-like cardiomyocytes phenotype. Many strategies have been applied such as co-culture of cardiomyocytes, with fibroblasts and endothelial cells, or conditioning them through biochemical factors and physical stimulations. Here, we focus on mechanical stimulation as it aims to mimic the different mechanical forces that heart receives during its development and the post-natal period. We describe the current strategies and the mechanical properties necessary to promote a positive response in cardiac tissues from different cell sources, distinguishing between passive stimulation, which includes stiffness, topography and static stress and active stimulation, encompassing cyclic strain, compression or perfusion. We also highlight how mechanical stimulation is applied in disease modelling.

This paper refers to cyclic shear strains (&gamma, c) and permanent shear strains (&gamma, p) of a soft cohesive soil, when both monotonic shear stresses (&tau, o) and cyclic shear stresses (&tau, c) are applied. The research is backed by an extensive experimental program with 139 cyclic simple shear tests that included identification and classification tests. These cyclic simple shear tests were conducted under different levels of stresses, &tau, o, before the cyclic phase. Laboratory tests were carried out on undisturbed samples from the Port of Barcelona, located in Spain on the Mediterranean coast, and characterized by a monotonic strength (&tau, max) approximately equal to 30% of the initial effective vertical stress (&sigma, &prime, ov). The samples were taken at depths between 29 and 52 m and correspond to an initial effective vertical stress between 277 and 413 kPa, respectively. In general, the results indicate that: (a) the combination of &tau, o and &tau, c controls the generation of &gamma, c and &gamma, p, (b) it is not always true that when &tau, o/&sigma, ov + &tau, c/&sigma, ov &asymp, &tau, max/&sigma, ov, the soil reaches failure cyclically, and (c) empirical relations useful for design can be established between &gamma, c, &gamma, p, and the number of cycles (N), for different relationships varying (&tau, ov) between 0% and 25%.

Background MicroRNAs (miRNAs) play a role in regulating osteogenic differentiation (OD) of mesenchymal stem cells by inhibiting mRNAs translation under cyclic strain. miR-503-3p was downregulated in OD of human adipose-derived stem cells (hASCs) in vivo under cyclic strain in our previous study, while it might target the Wnt/β-catenin (W-β) pathway. In this study, we explored miR-503-3p’s role in OD of hASCs under cyclic strain. Methods OD of hASCs was induced by cyclic strain. Bioinformatic and dual luciferase analyses were used to confirm the relationship between Wnt2/Wnt7b and miR-503-3p. Immunofluorescence was used to detect the effect of miR-503-3p on Wnt2/Wnt7b and β-catenin in hASCs transfected with miR-503-3p mimic and inhibitor. Mimic, inhibitor, and small interfering RNA (siRNA) transfected in hASCs to against Wnt2 and Wnt7b. Quantitative real-time PCR (RT-PCR) and western blot were used to examine the OD and W-β pathway at the mRNA and protein levels, respectively. Immunofluorescence was performed to locate β-catenin. ALP activity and calcium were detected by colorimetric assay. Results Results of immunophenotypes by flow cytometry and multi-lineage potential confirmed that the cultured cells were hASCs. Results of luciferase reporter assay indicated that miR-503-3p could regulate the expression levels of Wnt2 and Wnt7b by targeting their respective 3′-untranslated region (UTR). Under cyclic strain, gain- or loss-function of miR-503-3p studies by mimic and inhibitor revealed that decreasing expression of miR-503-3p could significantly bring about promotion of OD of hASCs, whereas increased expression of miR-503-3p inhibited OD. Furthermore, miR-503-3p high-expression reduced the activity of the W-β pathway, as indicated by lowering expression of Wnt2 and Wnt7b, inactive β-catenin in miR-503-3p-treated hASCs. By contrast, miR-503-3p inhibition activated the W-β pathway. Conclusions Collectively, our findings indicate that miR-503-3p is a negative factor in regulating W-β pathway by Wnt2 and Wnt7b, which inhibit the OD of hASCs under cyclic strain.

Objectives: Common autografts for ACL reconstruction include patellar (PT), hamstring (HT), and quadriceps tendons (QT). Various adverse outcomes, including osteoarthritis and revision risk, have been associated with different graft choices. While the time-zero material properties of autograft tissues are known, there is limited information on the biologic properties of autografts. In addition, the early differential responses of autograft fibroblasts to the biomechanical environment after surgery are not known. Our study objective was therefore to evaluate the in vitro responses of common ACL graft fibroblasts to clinically relevant strain levels. We hypothesized that fibroblasts from common autografts would exhibit differential gene expression and production of inflammatory biomarkers in response to cyclic strain. Methods: 12 QT, 12 PT, and 9 HT were harvested from skeletally mature dogs (n=12) (ACUC #9163, 9164). Tissues were digested and ACL graft fibroblasts were seeded onto BioFlex® plates (1 × 105 cells/well), and cultured for 48h prior to application of strain. Cells were subjected to mechanical stimulation (2-s strain, 10-s relaxation, 0.5 Hz frequency) with a biaxial sinusoidal waveform with 3 strains (stress deprivation-0%, physiologic-4%, and high-10%) for 5 days using a Flexcell. On day 5, media was collected for inflammatory biomarker analysis (PGE2, IL-8, KC, MCP-1) and RNA was extracted from cells for gene expression analysis with RT-PCR (COL1, COL2, COL3, MMP2, MMP3, MMP13, ELASTIN, SCX). Significant differences among graft types were set at pResults: Gene expression: QT had higher COL1 expression at 0% strain (pConclusion: Our study showed that fibroblasts from common ACL graft tissues exhibited different cellular responses to strain levels. At 4% strain, PT tended to have higher expression of extracellular matrix (ECM) genes and may have a more robust remodeling response under physiologic strain. Furthermore, the data from this study indicates that all autografts have a similar inflammatory metabolism at 4% strain, but the QT and PT may have a higher inflammatory response in stress deprivation (0%) and over strain (10%) conditions. Based on these data, we conclude that production of ECM and inflammatory response from ACL grafts are not only dependent on the mechanical environment, but also graft source.

Although mutations in the Lamin A/C gene (LMNA) cause a variety of devastating diseases, the pathological mechanism is often unknown. Lamin A/C proteins play a crucial role in forming a meshwork under the nuclear membrane, providing the nucleus with mechanical integrity and interacting with other proteins for gene regulation. Most LMNA mutations result in heart diseases, including some types that primarily have heart disease as the main pathology. In this study, we used cells from patients with different LMNA mutations that primarily lead to heart disease. Indeed, it is a mystery why a mutation to the protein in every nucleus of the body manifests as a disease of primarily the heart in these patients. Here, we aimed to investigate if strains mimicking those within the myocardial environment are sufficient to cause differences in cells with and without the LMNA mutation. To test this, a stretcher device was used to induce cyclic strain upon cells, and viability/proliferation, cytoskeleton and extracellular matrix organization, and nuclear morphology were quantified. The properties of cells with Hutchinson-Gilford progeria syndrome (HGPS) were found to be significantly different from all other cell lines and were mostly in line with previous findings. However, the properties of cells from patients who primarily had heart diseases were not drastically different when compared to individuals without the LMNA mutation. Our results indicated that cyclic strain alone was insufficient to cause any significant differences that could explain the mechanisms that lead to heart diseases in these patients with LMNA mutations.

Cell & tissue research (2021). doi:10.1007/s00441-021-03416-9, Published by Springer, Berlin ; Heidelberg

The microstructural stability during aging at 750 &deg, C of the &gamma, /&gamma, &prime, nickel-based superalloy AD730TM is investigated in this work. Strain-free aging and aging during fatigue tests are conducted, with a focus on the influence of the strain ratio, the maximum applied strain, and the cycle waveform (with or without dwell). Two classical mechanisms of &gamma, precipitates aging are identified at 750 &deg, C: the coarsening of small spherical &gamma, precipitates via the thermally-activated Ostwald ripening process and the coalescence of at least two precipitates into one. These mechanisms appeared to be concomitant during aging. It has been demonstrated that the coarsening kinetics of &gamma, precipitates can be described by a classical Lifshitz-Slyozow-Wagner (LSW) equation. The introduction of a cyclic strain during aging at 750 &deg, C increases the coarsening kinetics by means of changes in the volume diffusion of &gamma, forming elements and of constraint misfit effects. More precisely, it is shown that the higher the maximum applied strain and/or the strain rate, the higher the coarsening rates. Finally, dwell-fatigue promotes the activation of the &gamma, coalescence at 750 &deg, C.

Background/Aims: Increasing wall stress or biomechanical stretch experienced by arteries influences the initiation of atherosclerotic lesions. This initiation is mediated by Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), which are both effectors of the Hippo pathway. In this study, the functional roles of YAP/TAZ proteins in the regulation of the stretch-mediated programing of human umbilical arterial smooth muscle cells (HUASMCs) to a proliferative phenotype were examined. Methods: HUASMCs were seeded on a Matrigel-coated silicone chamber and subjected to biomechanical stretch for 24 h after 48 h of growth. YAP/TAZ small interfering RNA was used to specifically knockdown YAP/ TAZ expression in HUASMCs. Results: We observed that YAP/TAZ activation via biomechanical stretching is involved in the regulation of critical aspects of the HUASMC phenotypic switch. YAP/TAZ knockdown significantly attenuated the stretch-induced proliferative and pro-inflammatory phenotypes in HUASMCs. Furthermore, treatment with atorvastatin, an anti-atherosclerotic drug, attenuated the stretch-induced phenotypic switch of HUASMCs from the contractile to synthetic state by suppressing YAP/TAZ expression. Additional investigations demonstrated the role of stretch in inhibiting the Hippo pathway, leading to the activation of PI3-kinase (PI3K) and phosphoinositide dependent kinase (PDK1); the key molecule for the regulation of the PDK1 and Hippo complex interaction was Sav1. These results showed the importance of YAP/TAZ activation, induced by biomechanical stretch, in promoting atheroprone phenotypes in HUASMCs. Conclusion: Taken together, our findings revealed a mechanism by which YAP/TAZ activation contributes to the pathogenesis of atherosclerosis.

The cyclic strain approach was proposed in the 1980s as a potential alternative to the stress-based simplified liquefaction evaluation procedure. However, despite its fundamental basis and many positive attributes, it has not been embraced by practice. One reason for this may be the need to perform cyclic laboratory tests on undisturbed/reconstituted samples to develop a relationship among excess pore water pressure, cyclic strain amplitude, and number of applied strain cycles. Herein an alternative implementation of the strain-based procedure is proposed that circumvents this requirement, using a strain-based pore pressure generation model in lieu of laboratory test data. To assess the efficacy of the alternative implementation, several hundred small strain shear wave velocity (Vs) and Standard Penetration Test (SPT) field liquefaction case histories are evaluated. The results are compared with both field observations and with predictions from the stress-based procedures. It was found that the stress-based approach yielded considerably more accurate predictions compared to the cyclic strain approach. One likely reason for this is the strain-based procedure's inherent and potentially fatal limitation of ignoring the decrease in soil stiffness due to excess pore pressure when representing the earthquake loading in terms of shear strain amplitude and number of equivalent cycles.

Elber assumed a long time ago that ΔKeff is the driving force for fatigue crack growth (FCG), and his hypothesis is the basis for strip-yield models widely used to predict residual lives of cracked components. However, this hypothesis cannot explain many load sequence effects observed in practice. Hence, it is at least worth to verify if FCG models based on ΔKeff are indeed intrinsically better than concurrent models based on other principles. To do so, the same mechanics is used to predict FCG rates based both on Elber's ideas and on the alternative view that FCG is instead due to damage accumulation caused by the cyclic strain history ahead of the crack tip, an idea does not need or use the ΔKeff hypothesis. To compare both approaches fairly, FCG rates are estimated by damage accumulation using the cyclic strain ranges induced by plastic displacements calculated by the very same procedures used by strip-yield models, assuming there are strain limits associated both with FCG thresholds and with material toughness. Despite based on apparently conflicting principles, both models can reproduce quite well FCG curves, a somewhat surprising result. Besides confirming that data fitting cannot be used to prove any model superiority, this result indicates that the ΔKeff hypothesis is not a necessary requirement to explain the FCG behavior.

Purpose The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences.Methods The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 +/- 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging.Results No between-leg differences in triceps surae muscle strength were identified between dominant (2798 +/- 566 N) and non-dominant limb (2667 +/- 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P Conclusions These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size.

A wide range of techniques and methods are actively invented by clinicians and scientists who are dedicated to the field of musculoskeletal tissue regeneration. Biological, chemical, and physiological factors, which play key roles in musculoskeletal tissue development, have been extensively explored. However, physical stimulation is increasingly showing extreme importance in the processes of osteogenic and chondrogenic differentiation, proliferation and maturation through defined dose parameters including mode, frequency, magnitude, and duration of stimuli. Studies have shown manipulation of physical microenvironment is an indispensable strategy for the repair and regeneration of bone and cartilage, and biophysical cues could profoundly promote their regeneration. In this article, we review recent literature on utilization of physical stimulation, such as mechanical forces (cyclic strain, fluid shear stress, etc.), electrical and magnetic fields, ultrasound, shock waves, substrate stimuli, etc., to promote the repair and regeneration of bone and cartilage tissue. Emphasis is placed on the mechanism of cellular response and the potential clinical usage of these stimulations for bone and cartilage regeneration.

Adherent cells are generally able to reorient in response to cyclic strain. In three-dimensional tissues, however, extracellular collagen can affect this cellular response. In this study, a computational model able to predict the combined effects of mechanical stimuli and collagen on cellular (re)orientation was developed. In particular, a recently proposed computational model (which only accounts for mechanical stimuli) was extended by considering two hypotheses on how collagen influences cellular (re)orientation: collagen contributes to cell alignment by providing topographical cues (contact guidance); or collagen causes a spatial obstruction for cellular reorientation (steric hindrance). In addition, we developed an evolution law to predict cell-induced collagen realignment. The hypotheses were tested by simulating bi- or uniaxially constrained cell-populated collagen gels with different collagen densities, subjected to immediate or delayed uniaxial cyclic strain with varying strain amplitudes. The simulation outcomes are in agreement with previous experimental reports. Taken together, our computational approach is a promising tool to understand and predict the remodeling of collagenous tissues, such as native or tissue-engineered arteries and heart valves.

Two sets of strain-controlled cyclic triaxial tests were conducted to investigate soil liquefaction of clean sands. The first set involved conventional uniform strain amplitude cyclic tests, while the second set examined non-uniform strain amplitude cyclic tests. Comparisons were made between the two sets of results with respect to the generation of excess pore pressure and relationship between strain amplitude and stress path. In the case of uniform strain-controlled cyclic tests, larger strain amplitude produced more rapid generation of excess pore pressure. Conversely, for non-uniform strain-controlled tests, larger strain amplitudes may generate lower excess pore pressure instead. Such counter-intuitive phenomenon has design implications if irregular earthquake loadings in the field are incorrectly represented as equivalent uniform loading in the laboratory. Details are described in this paper.

This paper modified an Armstrong–Frederick-type plasticity model for investigating the stable cyclic deformation behavior of metallic materials with different sensitivity to nonproportional loadings. In the modified model, the nonproportionality factor and nonproportional cyclic hardening coefficient coupled with the Jiang–Sehitoglu incremental plasticity model were used to estimate the stable stress–strain responses of the two materials (1045HR steel and 304 stainless steel) under various tension–torsion strain paths. A new equation was proposed to calculate the nonproportionality factor on the basis of the minimum normal strain range. Procedures to determine the minimum normal strain range were presented for general multiaxial loadings. Then, the modified model requires only the cyclic strain hardening exponent and cyclic strength coefficient to determine the material constants. It is convenient for predicting the stable stress–strain responses of materials in engineering application. Comparisons showed that the modified model can reflect the effect of nonproportional cyclic hardening well.

Fatigue behaviors of the CoCrFeMnNi-based high-entropy alloy thin foils with different Al addition were investigated under dynamical bending fatigue loading. The results reveal that the Al addition can effectively decrease the cyclic strain localization and improve the fatigue resistance, which is associated with the reduced cyclic slip irreversibility. The physical reasons for such reduction can be attributed to the enhanced planar-slip ability induced by Al addition. Furthermore, the formation of BCC phases caused by 10 at.% Al addition also leads to a delay in the fatigue crack propagation.

Performance based seismic design (PBSD) procedures have been developed in recent years. Studies conducted in the past revealed that strain hardening ratio (SHR) used in numerical modeling can be influential on the performance of steel structural systems. In this paper, the effects of SHR on the performance assessment of eccentrically braced frame (EBF) buildings were studied by using FEMA P-58 methodology. The numerical model was validated using the pseudo-dynamic test results of the DUAREM structure. Seismic performance of six archetype EBFs with different number of stories and link length to bay width (e/L) ratios were evaluated under design basis earthquake (DBE), maximum considered earthquake (MCE), and collapse level earthquake (CLE). Irreparable residual drift, repair cost and unsafe placards were calculated for SHR ranging between 0 and 0.01. The results showed that the residual interstory drift ratio is more influenced by the SHR when compared with the interstory drift ratio, link rotation angle and story acceleration. The replacement decision was found to depend on the SHR, the number of stories, the e/L ratio, and the seismic hazard. Under MCE and CLE level events, almost all of the archetypes with SHR ≤ 0.003 required replacement while replacement can be avoided for some of the archetypes with SHR > 0.003. Under DBE level events, 3-story archetypes and 6-story archetypes with SHR ≥ 0.002 did not require replacement. Nine-story archetype with e/L = 0.08 required replacement for SHR = 0 only, while archetypes with e/L = 0.12 required replacement for SHR ≤ 0.003. The study demonstrated the strong influence and sensitivity of the repair cost to the SHR.

This paper presents test results of the effect of thermomechanical aging conducted at 100 °C, 200 °C and 300 °C on the fatigue life of EN AW-2024 alloy at ambient temperature. The results of fatigue tests conducted on specimens with no preliminary thermal and mechanical loadings (as-received specimens) are discussed. These results were accepted as a point of reference for the results of fatigue life tests of material previously subjected to simultaneous, preliminary thermal and mechanical loads. Conducted tests made it possible to determine the effect of creep pre-deformation at elevated temperature on the cyclic properties of the tested alloy. The shape of the hysteresis loop obtained for material subjected to different thermomechanical loadings was analyzed in detail. The character of obtained fatigue life curves and cyclic strain curves is also discussed. The direct relationship between these curves and material properties shaped in the process of preliminary creep, at different temperatures and under different load values, was indicated. At the same time, comparative analysis was conducted for fatigue fractures in as-received specimens and fractures obtained in specimens burdened by pre-deformation-related effects.

Thermomechanical fatigue (TMF) behavior of nitrogen enhanced 316LN stainless steel (with 0.14 wt.% N) is investigated under in-phase (IP) and out-of-phase (OP) conditions at cyclic strain amplitudes of ±0.25 to ±0.8% and with a temperature interval of 623–873 K. The study elucidates the differences in cyclic stress-strain response, TMF lives and fracture behavior of the material under IP and OP-TMF in the light of dynamic strain aging, thermal recovery and creep. The manifestations of these factors/phenomena are found to vary along stress-strain hysteresis loops, thereby leading to differences in cyclic strain hardening exponent ( n′ ) and coefficient ( K′ ) between the tensile and compressive branches of hysteresis loops. Irrespective of the imposed cyclic strain, transgranular fatigue failure is observed under OP-cycling in contrast to mixed-mode fracture under IP-cycling. The IP-cycling led to considerably lower cyclic life (i.e. 34–49%) compared to those under OP-TMF, with the life reduction being more significant (∼48.5%) at intermediate mechanical strain amplitudes of ±0.4 and ±0.6%. A comparison of the fatigue design curves under TMF with the corresponding isothermal fatigue curves (as per the RCC-MR design code) revealed a lack of conservatism in the latter.

At present, injuries or rupture of tendons are treated by surgical repair or conservative approaches with unpredictable clinical outcome. Alternative strategies to repair tendon defects without the undesirable side effects associated with the current options are needed. With this in mind, a tissue engineering approach has gained considerable attention as a promising strategy. Here we investigated a synthetic three-dimensional (3D) microenvironment able to interact with stem cells and inducing, via coupled biochemical and physical signals, their early commitment toward the tenogenic lineage. This multiphase 3D construct consisted of a braided hyaluronate elastic band merged with human bone marrow mesenchymal stem cells (hBMSCs) and poly-lactic-co-glycolic acid microcarriers loaded with human growth differentiation factor 5 (hGDF-5) by means of fibrin hydrogel. The multiphase structure allowed hBMSC culture under cyclic strain within a microenvironment where a controlled amount of hGDF-5 was regularly delivered. The cooperative biochemical and physical stimuli induced significantly increased expression of tenogenic markers, such as collagen type I and III, decorin, scleraxis, and tenascin-C, within only 3 days of dynamic hBMSC culture. This approach opens exciting perspectives for future development of engineered tendon tissue substitutes.

Elber's hypothesis that DeltaKeff can be assumed as the driving force for fatigue crack growth (FCG) is the basis for strip-yield models widely used to predict fatigue lives under variable amplitude loads, although it does not explain all load sequence effects observed in practice. To verify if these models are indeed intrinsically better, the mechanics of a typical strip-yield model is used to predict FCG rates based both on Elber's ideas and on the alternative view that FCG is instead due to damage accumulation induced by the cyclic strain history ahead of the crack tip, which does not need or use DeltaKeff ideas. The main purpose here is to predict FCG using the cyclic strains induced by the plastic displacements calculated by strip-yield procedures, assuming there are strain limits associated both the with the FCG threshold and with the material toughness. Despite based on conflicting principles, both models can reproduce quite well FCG data, a somewhat surprising result that deserves to be carefully analyzed.

Post-cyclic undrained shear strength is primarily controlled by the cyclic loading parameters and loading conditions. In the present paper, series of undrained constant strain cyclic triaxial test followed by strain-controlled monotonic shearing was carried out on normally consolidated marine clay specimens. An attempt was made to study the variation of post-cyclic undrained shear strength with the cyclic loading conditions namely staged cyclic loading and continuous cyclic loading. The effect of cyclic loading parameters such as cyclic strain amplitude, cyclic loading frequency and drainage after the undrained cyclic loading on post-cyclic strength and stiffness is also presented. It is observed from test results that the post-cyclic undrained strength and stiffness of the specimen is greatly influenced by the cyclic loading condition and drainage after cyclic loading. It was noted that due to the multiple stages of cyclic loading followed by pore pressure dissipation, the induced apparent overconsolidation ratio is higher for staged cyclic loading than the continuous cyclic loading conditions.

Rho GTPase-activating protein (Rho-GAP) and Rho GDP dissociation inhibitor (Rho- GDI) are two main negative regulators of Rho GTPase. Our previous work has found that Rho-GDI and Rho GTPase are involved in the response of human periodontal ligament (PDL) cells to mechanical stress. However, whether Rho-GAP also has a role in this process remains unknown. Here, we attempted to find the Rho-GAP gene that may be involved in pathological stretch-induced apoptosis of PDL cells. Human PDL fibroblasts were exposed to 20% cyclic strain for 6 hours or 24 hours, after which the expression levels of ARHGAP10, ARHGAP17, ARHGAP21, ARHGAP24 and ARHGAP28 were determined. Results showed that ARHGAP17 expression decreased the most obviously after treatment of stretch. In addition, ARHGAP17 overexpression abolished 20% cyclic strain-induced apoptosis. Therefore, ARHGAP17 has an important role in pathological stretch-induced apoptosis of human PDL fibroblasts. Moreover, we found that ARHGAP17 overexpression also alleviated cyclic strain-induced activation of Rac1/Cdc42, a major downstream target of ARHGAP17. Furthermore, two Rac1 inhibitors, NSC23766 and EHT 1864, both attenuated ARHGAP17 knockdown-mediated apoptosis in human PDL fibroblasts. Collectively, our data demonstrate that ARHGAP17 inhibits pathological cyclic strain-induced apoptosis in human PDL fibroblasts through inactivating Rac1/Cdc42. This study highlights the importance of Rho signalling in the response of human PDL fibroblasts to mechanical stress.

Cardiovascular tissue engineering offers potential solutions in a variety of clinical conditions such as heart failure, atherosclerosis, myocardial infarction, valve disease, congenital heart defects, and vascular access. While this represents a wide variety of applications, there are significant commonalities across the tissue types in the cardiovascular system that impact approaches to the development of engineered tissues. For example, endothelial cells that line the entire cardiovascular system change function under different shear stress conditions, while vascular smooth muscle cells respond to cyclic strain. This chapter discusses the tissues and cells that comprise the cardiovascular system as well as optimization of biomaterials for these tissue-engineering applications.

Artificial tissue presents a novel therapeutic approach for restoring function in severely damaged tissues. Macrophages have a central role in the vascularization and engraftment of implanted artificial tissue constructs. Our laboratory engineered magnetically responsive alginate scaffolds capable of delivering dynamic mechanical cues to scaffold associated cells in response to remote magnetic stimulation. In the current study, we investigated the ability of magnetically actuated scaffolds to modulate macrophage function in vitro and in vivo. We report that magnetically actuated scaffolds enhance the phenotype of classically activated (M1) macrophages, as shown by the increased expression of the M1 cell-surface marker CD86 and increased secretion of multiple M1 cytokines. Likewise, cyclic stretch applied directly to M1 macrophages using a commercial tension generating cell culture system increased the expression of CD86 and secretion of numerous M1 cytokines, corroborating the impact of cyclic strain on macrophage function. When scaffolds were implanted subcutaneously into mice and treated with magnetic stimulation days 5-8 post-implantation, there was increased infiltration of host macrophages and an increase in macrophage expression of CD86. Analysis of downstream regenerative outcomes revealed a subtle but encouraging trend towards an increase in scaffold vascularization and a decrease in fibrous capsule formation. These results advance our understanding of how remote-controlled mechanical cues, namely cyclic strain, impact macrophage function, and demonstrate the feasibility of using mechanically active materials to modulate the macrophage response in vivo.

It has been reported that cells sense and respond to mechanical stimuli. Mechanical vibration promotes the cell proliferation and the cell differentiation of osteoblast cells at 12.5 Hz and 50 Hz, respectively. It indicates that osteoblast cells have a mechansensing system for mechanical vibration. There may be some mechanosensors and we focus on cellular focal adhesions through which mechanical and biochemical signals may be transmitted from extracellular matrices into a cell. However, it is very difficult to directly apply mechanical stimuli to focal adhesions. We developed a magnetic micropillar substrate on which micron-sized pillars are deflected according to applied magnetic field strength and focal adhesions adhering to the top surface of the pillars are given mechanical stimuli. In this paper, we focus on intracellular calcium ion as a second messenger of cellular mechanosensing and investigate the mechanosensing mechanism of an osteoblast cell at focal adhesions under cyclic strain using a magnetic micropillar substrate. The experimental results indicate that the magnetic micropillars have enough performance to response to an electric current applied to a coil in an electromagnet and to apply the cyclic strain of less than 3% to a cell. In the cyclic strain of less than 3%, the calcium response of a cell was not observed.

Desmoglein 3 (Dsg3) plays a crucial role in cell-cell adhesion and tissue integrity. Increasing evidence suggests that Dsg3 acts as a regulator of cellular mechanotransduction, but little is known about its direct role in mechanical force transmission. The present study investigated the impact of cyclic strain and substrate stiffness on Dsg3 expression and its role in mechanotransduction in keratinocytes. A direct comparison was made with E-cadherin, a well-characterized mechanosensor. Exposure of oral and skin keratinocytes to equiaxial cyclic strain promoted changes in the expression and localization of junction assembly proteins. The knockdown of Dsg3 by siRNA blocked strain-induced junctional remodeling of E-cadherin and Myosin IIa. Importantly, the study demonstrated that Dsg3 regulates the expression and localization of yes-associated protein (YAP), a mechanosensory, and an effector of the Hippo pathway. Furthermore, we showed that Dsg3 formed a complex with phospho-YAP and sequestered it to the plasma membrane, while Dsg3 depletion had an impact on both YAP and phospho-YAP in their response to mechanical forces, increasing the sensitivity of keratinocytes to the strain or substrate rigidity-induced nuclear relocation of YAP and phospho-YAP. Plakophilin 1 (PKP1) seemed to be crucial in recruiting the complex containing Dsg3/phospho-YAP to the cell surface since its silencing affected Dsg3 junctional assembly with concomitant loss of phospho-YAP at the cell periphery. Finally, we demonstrated that this Dsg3/YAP pathway has an influence on the expression of YAP1 target genes and cell proliferation. Together, these findings provide evidence of a novel role for Dsg3 in keratinocyte mechanotransduction.

Endothelial cells (ECs) are continuously subjected to fluid wall shear stress (WSS) and cyclic strain caused by pulsatile blood flow and pressure. It is well established that these hemodynamic forces each play important roles in vascular disease, but their combined effects are not well understood. ECs remodel in response to both WSS and cyclic strain to align along the vessel axis, but in areas prone to atherogenesis, such an alignment is absent. In this perspective, experimental and clinical findings will be reviewed, which have revealed the characteristics of WSS and cyclic strain, which are associated with atherosclerosis, spanning studies on whole blood vessels to individual cells to mechanosensing molecules. Examples are described regarding the use of computational modeling to elucidate the mechanisms by which EC alignment contributes to mechanical homeostasis. Finally, the need to move toward an integrated understanding of how hemodynamic forces influence EC mechanotransduction is presented, which holds the potential to move our currently fragmented understanding to a true appreciation of the role of mechanical stimuli in atherosclerosis.

Background The Wnt/β-catenin pathway is involved in the osteogenic differentiation of human adipose-derived stem cells (hASCs) under cyclic strain. Very little is known about the role of microRNAs in these events. Methods Cells were obtained using enzyme digestion methods, and proliferation was detected using Cell Counting Kit 8. Cell cycles and immunophenotypes were detected by flow cytometry. The multilineage potential of hASCs was induced by induction media. Cyclic strain was applied to hASCs (0.5 Hz, 2 h/day, 6 days) to induce osteogenic differentiation and miRNA changes. Bioinformatic and dual-luciferase analyses confirmed lymphoid enhancer factor 1 (LEF1) as a potential target of let-7i-3p. The effect of let-7i-3p on LEF1 in hASCs transfected with a let-7i-3p mimic and inhibitor was analyzed by immunofluorescence. hASCs were transfected with a let-7i-3p mimic, inhibitor, or small interfering RNA (siRNA) against LEF1 and β-catenin. Quantitative real-time PCR (qPCR) and western blotting were performed to examine the osteogenic markers and Wnt/β-catenin pathway at the mRNA and protein levels, respectively. Immunofluorescence and western blotting were performed to confirm the activation of the Wnt/β-catenin pathway. Results Flow cytometry showed that 82.12% ± 5.83% of the cells were in G1 phase and 17.88% ± 2.59% of the cells were in S/G2 phase; hASCs were positive for CD29, CD90, and CD105. hASCs could have the potential for osteogenic, chondrogenic, and adipogenic differentiation. MicroRNA screening via microarray showed that let-7i-3p expression was decreased under cyclic strain. Bioinformatic and dual-luciferase analyses confirmed that LEF1 in the Wnt/β-catenin pathway was the target of let-7i-3p. Under cyclic strain, the osteogenic differentiation of hASCs was promoted by overexpression of LEF1and β-catenin and inhibited by overexpression of let-7i-3p. hASCs were transfected with let-7i-3p mimics and inhibitor. Gain- or loss-of-function analyses of let-7i-3p showed that the osteogenic differentiation of hASCs was promoted by decreased let-7i-3p expression and inhibited by increased let-7i-3p expression. Furthermore, high LEF1 expression inactivated the Wnt/β-catenin pathway in let-7i-3p-enhanced hASCs. In contrast, let-7i-3p inhibition activated the Wnt/β-catenin pathway. Conclusions Let-7i-3p, acting as a negative regulator of the Wnt/β-catenin pathway by targeting LEF1, inhibits the osteogenic differentiation of hASCs under cyclic strain in vitro.