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Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo . In this study, we propose that rolling–sliding–compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers often ignore the importance of biochemical factors to the growth and development of engineered cartilage. In our point of view, only by fully considering synergistic effects of mechanical and biochemical factors can we find appropriate culture conditions for functional cartilage constructs. Once again, rolling–sliding–compression load under appropriate biochemical conditions may be conductive to realize the adaptive development between the structure and function of engineered cartilage in vitro .

Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules, decellularized extracellular matrix (ECM) may trigger and enhance stem cell proliferation and differentiation. Here, we investigated the controlled release of transforming growth factor beta (TGF-β1) as an active mediator of mesenchymal stromal cells (MSCs) in a biocompatible scaffold and mechanical stimulation for cartilage tissue engineering. ECM-derived hydrogel with TGF-β1-loaded alginate-based microspheres (MSs) was created to promote human MSC chondrogenic development. Ex vivo explants and a complicated multiaxial loading bioreactor replicated the physiological conditions. Hydrogels with/without MSs and TGF-β1 were highly cytocompatible. MSCs in ECM-derived hydrogel containing TGF-β1/MSs showed comparable chondrogenic gene expression levels as those hydrogels with TGF-β1 added in culture media or those without TGF-β1. However, constructs with TGF-β1 directly added within the hydrogel had inferior properties under unloaded conditions. The ECM-derived hydrogel group including TGF-β1/MSs under loading circumstances formed better cartilage matrix in an ex vivo osteochondral defect than control settings. This study demonstrates that controlled local delivery of TGF-β1 using MSs and mechanical loading is essential for neocartilage formation by MSCs and that further optimization is needed to prevent MSC differentiation towards hypertrophy.

Damage accumulation in the bone under continuous daily loading causes local mechanical overloading known to induce osteocyte apoptosis, which promotes bone resorption to repair bone damage. However, only a few studies have investigated the mechanism of apoptosis in mechanically overloaded osteocytes. As mechanically stimulated osteocytes produce nitric oxide (NO), which triggers apoptosis in various cell types, we aimed to elucidate the mechanism underlying apoptosis in mechanically overloaded osteocytes, focusing on intracellular NO. To investigate the effects of force magnitude on apoptosis and intracellular NO production, we isolated osteocytes from DMP1-EGFP mice and subjected them to quantitative local forces via fibronectin-coated micro beads targeting integrin on the cell surface using a magnetic tweezer. Cell shrinkage was microscopically examined, and intracellular NO production was visualized using DAR-4 M. Mechanical stimulation revealed relationships between force magnitude, apoptosis, and intracellular NO production. The application of a smaller force resulted in no significant cell shrinkage or intracellular NO production; however, a larger force caused a rapid increase in intracellular NO production followed by cell shrinkage. Besides, intracellular NOS (NO synthase) inhibition and NO donation revealed the pro-apoptotic roles of NO in osteocytes. L-NAME (NOS inhibitor)-treated cells displayed no significant shrinkage under a larger force, whereas SNP (NO donor)-treated cells showed cell shrinkage and Annexin V fluorescence, indicating apoptosis. Collectively, our study demonstrates that larger force leads to NO production-mediated osteocyte shrinkage, implying an initial apoptotic response and highlighting the importance of NO production in bone damage.

Objectives To identify molecular clusters and establish a scoring model based on mechanical stimulus-related genes (MSRGs) for predicting the prognosis of breast cancer patients and understanding the role of mechanical stimuli in the breast tumor microenvironment (TME). Methods We utilized bulk and single-cell RNA sequencing analysis to characterize MSRGs associated with breast cancer prognosis. Unsupervised consensus molecular clustering was applied to identify distinct clusters based on overall survival-associated MSRGs from The Cancer Genome Atlas (TCGA) database. The scoring model was constructed by LASSO-Cox method and validated. Additionally, single-cell RNA sequencing analysis, along with in vitro and in vivo experiments, were conducted to further investigate the role of the model in breast cancer. Results We identified 23 overall survival-associated MSRGs and established two molecular subgroups with distinct survival outcomes. A prognostic signature incorporating 15 MSRGs was developed and validated, demonstrating its predictive capability for overall survival of breast cancer patients. The nomogram integrating clinical characteristics and the mechanical stimulus-related risk score exhibited promising predictive accuracy. The low-risk group displayed an immune \"hot\" phenotype with increased immune cell infiltration, while the high-risk group exhibited resistance to conventional chemotherapy but potential sensitivity to Sepantronium bromide. By using the SCISSOR algorithm, we provide evidence at single-cell resolution for the impact of mechanical stimulation on tumor immune microenvironment. The in vivo and in vitro assays demonstrated that knockdown of TEX19 significantly suppressed breast tumor proliferation. Conclusion We developed a pioneering prognostic signature incorporating MSRGs in breast cancer, with a particular focus on mechanical stimuli may influence breast cancer prognosis by remodeling the immune microenvironment. The findings highlighted the importance of personalized treatment strategies and provide new insights into the role of mechanical forces in breast tumor biology.

In this work, we propose a mechanobiological atheroma growth model modulated by a new haemodynamic stimulus. To test this model, we analyse the development of atheroma plaques in patient-specific bifurcations of carotid arteries for a total time of 30 years. In particular, eight geometries (left or right carotid arteries) were segmented from clinical images and compared with the solutions obtained computationally to validate the model. The influence of some haemodynamical stimuli on the location and size of plaques is also studied. Plaques predicted by the mechanobiological models using the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and a new index proposed in this work are compared. The new index predicts the shape index of the endothelial cells as a combination of TAWSS and OSI values and was fitted using data from the literature. The mechanobiological model represents an evolution of the one previously proposed by the authors. This model uses Navier-Stokes equations to simulate blood flow along the lumen in the transient mode. It also employs Darcy's law and Kedem-Katchalsky equations for plasma and substance flow across the endothelium using the three-pore model. The mass balances of all the substances that have been considered in the model are implemented by convection-diffusion-reaction equations, and finally the growth of the plaques has been computed. The results show that by using the new mechanical stimulus proposed in this study, prediction of plaques is, in most cases, better than only using TAWSS or OSI with a minimal and maximal errors on stenosis ratio of 2.77 and 32.89 %, respectively. However, there are a few geometries in which haemodynamics cannot predict the location of plaques, and other biological or genetic factors would be more relevant than haemodynamics. In particular, the model predicts correctly eleven of the fourteen plaques presented in all the geometries considered. Additionally, a healthy geometry has been computed to check that plaque is not developed with the model in this case.

The material bone has attracted the attention of material scientists due to its fracture resistance and ability to self-repair. A mechanoregulated exchange of damaged bone using newly synthesized material avoids the accumulation of fatigue damage. This remodeling process is also the basis for structural adaptation to common loading conditions, thereby reducing the probability of material failure. In the case of fracture, an initial step of tissue formation is followed by a mechanobiological controlled restoration of the pre-fracture state. The present perspective focuses on these mechanobiological aspects of bone remodeling and healing. Specifically, the role of the control function is considered, which describes mechanoregulation as a link between mechanical stimulation and the local response of the material through changes in structure or material properties. Mechanical forces propagate over large distances leading to a complex non-local feedback between mechanical stimulation and material response. To better understand such phenomena, computer models are often employed. As expected from control theory, negative and positive feedback loops lead to entirely different time evolutions, corresponding to stable and unstable states of the material system. After some background information about bone remodeling and healing, we describe a few representative models, the corresponding control functions, and their consequences. The results are then discussed with respect to the potential design of synthetic materials with specific self-repair properties.

The response of the metal–organic framework aluminum-1,4-cyclohexanedicarboxylate or Al-CAU-13 (CAU: Christian Albrecht University) to the application of thermal and mechanical stimuli was investigated using synchrotron powder X-ray diffraction (SPXRD). Variable temperature in situ SPXRD data, over the range 80–500 K, revealed a complex evolution of the structure of the water guest containing Al-CAU-13•H2O, the dehydration process from ca. 310 to 370 K, and also the evolution of the guest free Al-CAU-13 structure between ca. 370 and 500 K. Rietveld refinement allowed this complexity to be rationalized in the different regions of heating. The Berman thermal Equation of State was determined for the two structures (Al-CAU-13•H2O and Al-CAU-13). Diamond anvil cell studies at elevated pressure (from ambient to up to ca. 11 GPa) revealed similarities in the structural responses on application of pressure and temperature. The ability of the pressure medium to penetrate the framework was also found to be important: non-penetrating silicone oil caused pressure induced amorphization, whereas penetrating helium showed no plastic deformation of the structure. Third-order Vinet equations of state were calculated and show Al-CAU-13•H2O is a hard compound for a metal–organic framework material. The mechanical response of Al-CAU-13, with tetramethylpyrazine guests replacing water, was also investigated. Although the connectivity of the structure is the same, all the linkers have a linear e,e-conformation and the structure adopts a more open, wine-rack-like arrangement, which demonstrates negative linear compressibility (NLC) similar to Al-MIL-53 and a significantly softer mechanical response. The origin of this variation in behavior is attributed to the different linker conformation, demonstrating the influence of the S-shaped a,a-conformation on the response of the framework to external stimuli.

In nature, terrestrial plants experience many kinds of external mechanical stimulation and respond by triggering a network of signaling events to acclimate their growth and development. Some environmental cues, especially wind, recur on time scales varying from seconds to days. Plants thus have to adapt their sensitivity to such stimulations to avoid constitutive activation of stress responses. The study of plant mechanosensing has been attracting more interest in the last two decades, but plant responses to repetitive mechanical stimulation have yet to be described in detail. In this mini review, alongside classic experiments we survey recent descriptions of the kinetics of plant responses to recurrent stimulation. The ability of plants to modulate their responses to recurrent stimulation at the molecular, cellular, or organ scale is also relevant to other abiotic stimuli. It is possible that plants reduce their responsiveness to environmental signals as a function of their recurrence, recovering full sensitivity several days later. Finally, putative mechanisms underlying mechanosensing regulation are discussed.

Electronic skins (e-skins) are devices that can respond to mechanical stimuli and enable robots to perceive their surroundings. A great challenge for existing e-skins is that they may easily fail under extreme mechanical conditions due to their multilayered architecture with mechanical mismatch and weak adhesion between the interlayers. Here we report a flexible pressure sensor with tough interfaces enabled by two strategies: quasi-homogeneous composition that ensures mechanical match of interlayers, and interlinked microconed interface that results in a high interfacial toughness of 390 J·m −2 . The tough interface endows the sensor with exceptional signal stability determined by performing 100,000 cycles of rubbing, and fixing the sensor on a car tread and driving 2.6 km on an asphalt road. The topological interlinks can be further extended to soft robot-sensor integration, enabling a seamless interface between the sensor and robot for highly stable sensing performance during manipulation tasks under complicated mechanical conditions. E-skins often have poor interfaces that lead to unstable performances. Here, authors report e-skins with a quasi-homogeneous composition and bonded micro-structured interfaces, through which both the sensitivity and stability of the devices are improved.