Effect Of Mechanical Loading Research Articles

Mechanical loading modulates phosphate related genes in rat bone.

Mechanical loading determines bone mass and bone structure, which involves many biochemical signal molecules. Of these molecules, Mepe and Fgf23 are involved in bone mineralization and phosphate homeostasis. Thus, we aimed to explore whether mechanical loading of bone affects factors of phosphate homeostasis. We studied the effect of mechanical loading of bone on the expression of Fgf23, Mepe, Dmp1, Phex, Cyp27b1, and Vdr. Twelve-week old female rats received a 4-point bending load on the right tibia, whereas control rats were not loaded. RT-qPCR was performed on tibia mRNA at 4, 5, 6, 7 or 8 hours after mechanical loading for detection of Mepe, Dmp1, Fgf23, Phex, Cyp27b1, and Vdr. Immunohistochemistry was performed to visualise FGF23 protein in tibiae. Serum FGF23, phosphate and calcium levels were measured in all rats. Four-point bending resulted in a reduction of tibia Fgf23 gene expression by 64% (p = 0.002) and a reduction of serum FGF23 by 30% (p<0.001), six hours after loading. Eight hours after loading, Dmp1 and Mepe gene expression increased by 151% (p = 0.007) and 100% (p = 0.007). Mechanical loading did not change Phex, Cyp27b1, and Vdr gene expression at any time-point. We conclude that mechanical loading appears to provoke both a paracrine as well as an endocrine response in bone by modulating factors that regulate bone mineralization and phosphate homeostasis.

Multi-material topology optimization for maximizing structural stability under thermo-mechanical loading

Mechanical structures are often simultaneously subjected to thermal and mechanical loading, both of which can lead to buckling failure. Developing efficient structural forms with better capacity for stability is important to keep structures safe. This study aims to optimize structural buckling capacity by using a density-based topology optimization scheme. Instead of treating the mechanical and thermal loadings as a single coupled part in the linearized buckling analysis, the effects of mechanical and thermal loadings are decoupled, which allows to separately analyze and optimize buckling aspects induced by mechanical or thermal loading. Two optimization models based on the decoupled analysis models are developed to respectively maximize the critical load factor of buckling induced by mechanical loading under a specified thermal loading and buckling induced by thermal loading under a specified mechanical loading. Further, based on a three-phase material model, a multi-material topology optimization scheme is employed to optimize the buckling capacity of active structures made of structural and actuating materials and prestressed structures containing prestressed components. The actuation effects are mimicked by the thermal loading of active material. The sensitivities of the objective functions and constraints are derived through the adjoint technique, and the method of moving asymptotes (MMA) is employed to solve the topology optimization problems. Numerical examples are adopted to verify the effectiveness of the proposed approach.

Blocking toll-like receptor 4 mitigates static loading induced pro-inflammatory expression in intervertebral disc motion segments

While the anabolic effects of mechanical loading on the intervertebral disc (IVD) have been extensively studied, inflammatory responses to loading have not been as well characterized. Recent studies have highlighted a significant role of innate immune activation, particularly that of toll-like receptors (TLRs), in IVD degeneration. Biological responses of intervertebral disc cells to loading depend on many factors that include magnitude and frequency. The goals of this study were to characterize the inflammatory signaling changes in response to static and dynamic loading of IVD and investigate the contributions of TLR4 signaling in response to mechanical loading. Rat bone-disc-bone motion segments were loaded for 3 hr under a static load (20 % strain, 0 Hz) with or without an additional low-dynamic (4 % dynamic strain, 0.5 Hz) or high-dynamic (8 % dynamic strain, 3 Hz) strain, and results were compared to unloaded controls. Some samples were also loaded with or without TAK-242, an inhibitor of TLR4 signaling. The magnitude of NO release into the loading media (LM) was correlated with the applied frequency and strain magnitudes across different loading groups. Injurious loading profiles, such as static and high-dynamic, significantly increased Tlr4 and Hmgb1 expression while this result was not observed in the more physiologically relevant low-dynamic loading group. TAK-242 co-treatment decreased pro-inflammatory expression in static but not dynamic loaded groups, suggesting that TLR4 plays a direct role in mediating inflammatory responses of IVD to static compression. Overall, the microenvironment induced by dynamic loading diminished the protective effects of the TAK-242, suggesting that TLR4 plays a direct role in mediating inflammatory responses of IVD to static loading injury.

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair.

The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.

The Effects of Mechanical Load on Chondrogenic Responses of Bone Marrow Mesenchymal Stem Cells and Chondrocytes Encapsulated in Chondroitin Sulfate-Based Hydrogel.

Articular cartilage is vulnerable to mechanical overload and has limited ability to restore lesions, which leads to the development of chronic diseases such as osteoarthritis (OA). In this study, the chondrogenic responses of human bone marrow mesenchymal stem cells (BMMSCs) and OA cartilage-derived chondrocytes in 3D chondroitin sulfate-tyramine/gelatin (CS-Tyr)/Gel) hydrogels with or without experimental mechanical load have been investigated. Chondrocytes were smaller in size, had slower proliferation rate and higher level of intracellular calcium (iCa2+) compared to BMMSCs. Under 3D chondrogenic conditions in CS-Tyr/Gel with or without TGF-β3, chondrocytes more intensively secreted cartilage oligomeric matrix protein (COMP) and expressed collagen type II (COL2A1) and aggrecan (ACAN) genes but were more susceptible to mechanical load compared to BMMSCs. ICa2+ was more stably controlled in CS-Tyr/Gel/BMMSCs than in CS-Tyr/Gel/chondrocytes ones, through the expression of L-type channel subunit CaV1.2 (CACNA1C) and Serca2 pump (ATP2A2) genes, and their balance was kept more stable. Due to the lower susceptibility to mechanical load, BMMSCs in CS-Tyr/Gel hydrogel may have an advantage over chondrocytes in application for cartilage regeneration purposes. The mechanical overload related cartilage damage in vivo and the vague regenerative processes of OA chondrocytes might be associated to the inefficient control of iCa2+ regulating channels.

Electrochemical Response of Alkaline Batteries Subject to Quasi-Static and Dynamic Loading

Electrochemical changes were successfully monitored through the coupling of external loading, electrochemical impedance spectroscopy (EIS), and distribution of relaxation times (DRT) analysis. The development of the testing methods allows for detailed observation of changes due to mechanical loading and distinguishes responses between different cell geometries. Comparison of the force vs displacement, voltage vs displacement, and distribution of relaxation times plots to the different cell geometries display failure modes specific to geometry as well as the impact of different loading profiles. Numerical modeling confirmed the movement within individual cells and predicted locations with the most deformation based on the external loading condition applied. The results gathered from combining mechanical loading, electrochemical response, and numerical modeling, yield a viable approach to establishing an improved understanding of the effects of mechanical loading on the electrochemical response of multiple battery geometries and the methods herein may be extensible to additional battery chemistries.

Forecasting the Durability of Composite Materials Products under the Combined Action of Mechanical Loads and Chemically Aggressive Media

Structures made of composite materials with a complex structure during operation are subjected to the combined effects of mechanical loads and aggressive media, which initiate the accumulation of damage in the material. As a result, premature destruction of structures, buildings, structures are possible. To prevent emergencies, it is necessary to be able to assess the resource of structures at any time. The article analyzes the previously proposed methodology of mathematical modeling of degradation processes, calculation and prediction of durability, resource structures, based on the application of the fundamental laws of mechanics of deformable solids and physico-chemical kinetics. The mechanisms of degradation of composites, methods of experimental determination of the main degradation parameters, conditions for calculating the durability of two groups of limit states are considered.

Mechanical and Thermal Load Effect on Piston Crown of a Biogas Engine: A Simulation Approach

This paper presents the study results on stress and deformation of the piston crown of a biogas engine converted from a conventional diesel engine using dedicated software. The original diesel engine was modified to reduce the compression ratio to suit biogas fuel. The original engine's combustion chamber and compression ratio were changed by modifying the piston crown to a heron type. The parameters of in-cylinder pressure and temperature were determined by the thermodynamic simulation software AVL Boost. Research results show that the in-cylinder pressure decreased compared to diesel when using biogas fuel, but the temperature increased. The infinite element method-based software was used to simulate the effects of mechanical and thermal load on stress and deformation on the piston crown of the biogas engine. As modeling with maximum pressure and temperature, the maximum stress on the piston crown was 3.425x109 N/m2 and 4.224x109 N/m2 for diesel and biogas. However, the maximum deformation in the biogas case was lesser than diesel, 0.3037 and 0.4186 mm. The minimum safety factor was 0.1012 and 0.0891 for diesel and biogas models, respectively.

THE ROLE OF PPARδ-DRIVEN β-OXIDATION IN BONE HEALTH DURING AGING

Abstract Musculoskeletal disorders are a significant complication of aging, leading to increased morbidity and mortality. However, current understanding of the mechanisms by which aging affects skeletal health is limited. Osteocytes are the most numerous and long-lived bone cells and play key roles in maintaining bone mass by responding to anabolic signals such as mechanical loading. Energy metabolism is dysregulated in many cells with aging, however regulation of energy metabolism in osteocytes and how this is affected during aging and by mechanical loading remains undefined. To investigate this, we first used IDG-SW3 osteocyte cells to determine the effects of mechanical loading on osteocytes in vitro by applying fluid flow shear stress (FFSS). FFSS increased Pparδ and Cpt1 expression, key promoters of fatty acid β-oxidation (FAO). Pharmacological antagonism of PPARδ or CPT1 resulted in dysregulated expression of key bone remodeling genes and impaired ATP release in response to FFSS. In vivo, mechanical loading significantly increased FAO in tibia cortical bone. However, FAO was impaired in the bones from aged mice. To further elucidate the role of osteocyte FAO, we deleted PPARδ specifically in osteocytes (PPARδ cKO), which resulted in decreased FAO and bone volume in female PPARδ cKO mice. Lastly, treatment of aging mice with the PPARδ activator GW0742 resulted in significantly increased bone mineral content, density and trabecular bone volume. These findings suggest important functions of osteocyte energy metabolism during aging and with mechanical loading on bone and identify PPARδ-driven FAO as a novel therapeutic target for improving skeletal health with aging.

Applied-strain-promoted oxidation of Nickel: Insights from ReaxFF molecular dynamic simulation

Ni-based superalloy components are often subjected to applied stress in service. Besides creep and fatigue, the impact of applied stress on metal oxidation corrosion should not be underestimated. In this work, we studied the oxidation behavior of Ni under different applied strains by molecular dynamics simulation with ReaxFF potential. Results show that the oxidation begins with the outward diffusion of random Ni atoms from the surface, and both applied compressive strain and applied tensile strain can activate the Ni surface, advancing the oxidation start time and promoting oxidation. The applied tensile strain promotes oxidation by promoting the inward diffusion of oxygen atoms and inhibiting the outward diffusion of nickel atoms, while the applied compression strain does the opposite. This work provides a better understanding of the effect of mechanical loading on oxidation kinetics, which is helpful for the improvement of anti-corrosion measures of Ni-based superalloys.

Mechanical loading effect on the hydrogen uptake of tempered martensite steel: Elastic strain effect vs. plastic strain effect

The effects of mechanical loading on hydrogen uptake were investigated by thermal desorption experiments under various combinations of hydrogen charging and loading conditions. The diffusible hydrogen content increased with increasing elastic and plastic strains. The increase in diffusible hydrogen content per elastic strain was larger than that per plastic strain.

Effect of Mechanical Loading of Senescent Myoblasts on Their Myogenic Lineage Progression and Survival

During aging, muscle cell apoptosis increases and myogenesis gradually declines. The impaired myogenic and survival potential of the aged skeletal muscle can be ameliorated by its mechanical loading. However, the molecular responses of aged muscle cells to mechanical loading remain unclear. This study examined the effect of mechanical loading of aged, proliferating, and differentiated myoblasts on the gene expression and signaling responses associated with their myogenic lineage progression and survival. Control and aged C2C12 cells were cultured on elastic membranes and underwent passive stretching for 12 h at a low frequency (0.25 Hz) and different elongations, varying the strain on days 0 and 10 of myoblast differentiation. Activation of ERK1/2 and Akt, and the expression of focal adhesion kinase (FAK) and key myogenic regulatory factors (MRFs), MyoD and Myogenin, were determined by immunoblotting of the cell lysates derived from stretched and non-stretched myoblasts. Changes in the expression levels of the MRFs, muscle growth, atrophy, and pro-apoptotic factors in response to mechanical loading of the aged and control cells were quantified by real-time qRT-PCR. Mechanical stretching applied on myoblasts resulted in the upregulation of FAK both in proliferating (day 0) and differentiated (day 10) cells, as well as in increased phosphorylation of ERK1/2 in both control and aged cells. Moreover, Akt activation and the expression of early differentiation factor MyoD increased significantly after stretching only in the control myoblasts, while the late differentiation factor Myogenin was upregulated in both the control and aged myoblasts. At the transcriptional level, mechanical loading of the proliferating myoblasts led to an increased expression of IGF-1 isoforms and MRFs, and to downregulation of muscle atrophy factors mainly in control cells, as well as in the upregulation of pro-apoptotic factors both in control and aged cells. In differentiated cells, mechanical loading resulted in an increased expression of the IGF-1Ea isoform and Myogenin, and in the downregulation of atrophy and pro-apoptotic factors in both the control and aged cells. This study revealed a diminished beneficial effect of mechanical loading on the myogenic and survival ability of the senescent muscle cells compared with the controls, with a low strain (2%) loading being most effective in upregulating myogenic/anabolic factors and downregulating atrophy and pro-apoptotic genes mainly in the aged myotubes.

The role of mechanical loading in bcc-hcp phase transition: tension-compression asymmetry and twin formation

In response to temperature or pressure changes, many body-centered cubic (bcc) materials undergo martensitic bcc-hcp phase transformation, which is known to produce rich martensite microstructure with internal twins. Mechanical loading is also known to have a huge impact on martensitic phase transformation. In this work, we integrate atomistic simulations with theoretical calculations to investigate the effect of mechanical loading on the martensite microstructure. The calculations of deformation gradients and transformation strains reveal that the {101¯1} transformation twins and {101¯2} transformation twins are favored by opposite loading directions. Furthermore, the initial {112} twin in the bcc phase is transformed into {112¯2} and {112¯1} twins after the phase transformation. The results reveal the critical role of mechanical loading in the formation of the specific transformation twinning, which could offer a novel strategy to engineer twin microstructure using designed thermomechanical processing.

Effects of hindlimb unloading and subsequent reloading on the structure and mechanical properties of Achilles tendon-to-bone attachment.

While muscle and bone adaptations to deconditioning have been widely described, few studies have focused on the tendon enthesis. Our study examined the effects of mechanical loading on the structure and mechanical properties of the Achilles tendon enthesis. We assessed the fibrocartilage surface area, the organization of collagen, the expression of collagen II, the presence of osteoclasts, and the tensile properties of the mouse enthesis both after 14 days of hindlimb suspension (HU) and after a subsequent 6 days of reloading. Although soleus atrophy was severe after HU, calcified fibrocartilage (CFc) was a little affected. In contrast, we observed a decrease in non-calcified fibrocartilage (UFc) surface area, collagen fiber disorganization, modification of morphological characteristics of the fibrocartilage cells, and altered collagen II distribution. Compared to the control group, restoring normal loads increased both UFc surface area and expression of collagen II, and led to a crimp pattern in collagen. Reloading induced an increase in CFc surface area, probably due to the mineralization front advancing toward the tendon. Functionally, unloading resulted in decreased enthesis stiffness and a shift in site of failure from the osteochondral interface to the bone, whereas 6 days of reloading restored the original elastic properties and site of failure. In the context of spaceflight, our results suggest that care must be taken when performing countermeasure exercises both during missions and during the return to Earth.

Controlled mechanical loading improves bone regeneration by regulating type H vessels in a S1Pr1-dependent manner.

Despite the best treatment, approximately 10% of fractures still face undesirable repair and result in delayed unions or non-unions. Dynamic mechanical stimulation promotes bone formation, when applied at the correct time frame, with optimal loading magnitude, frequency, and repetition. Controlled mechanical loading significantly increases osteogenic cells during the matrix deposition phase of bone repair. In the bone defect, the blood vessel network guides the initial bone formation activities. A unique blood vessel subtype (Type H) exists in bone, which expresses high levels of CD31 and endomucin, and functions to couple angiogenesis and osteogenesis. However, how this form of controlled mechanical loading regulates the Type H vessels and promotes bone formation is still not clear. Sphingosine 1-phosphate (S1P) participates in the bone anabolic process and is a key regulator of the blood vessel. Its receptor, sphingosine 1-phosphate receptor 1 (S1Pr1), is a mechanosensitive protein that regulates vascular integrity. Therefore, we hypothesis that controlled anabolic mechanical loading promotes bone repair by acting on Type H vessels. To study the effect of S1Pr1 on loading induced-bone repair, we utilized a stabilized tibial defect model, which allows for the application of anabolic mechanical loading. Mechanical loading upregulated S1Pr1 within the entire defect, with up to 80% expressed in blood vessels, as observed by deep tissue imaging. Additionally, S1Pr1 antagonism by W146 inhibited the anabolic effects of mechanical loading. We showed that mechanical loading or activating S1Pr1 could induce YAP nuclear translocation, a key regulator in the cell's mechanical response, in endothelial cells (ECs) in vitro. Inhibition of S1Pr1 in endothelial cells by siRNA reduced loading-induced YAP nuclear translocation and expressions of angiogenic genes. In vivo, YAP nuclear translocation in Type H vessels was up-regulated after mechanical loading but was inhibited by antagonizing S1Pr1. S1Pr1 agonist, FTY720, increased bone volume and Type H vessel volume, similar to that of mechanical stimulation. In conclusion, controlled anabolic mechanical loading enhanced bone formation mainly through Type H vessels in a S1Pr1-dependent manner.

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock.

The biomechanical environment plays a key role in regulating cartilage formation, but the current understanding of mechanotransduction pathways in chondrogenic cells is incomplete. Amongthe combination of external factors that control chondrogenesis are temporal cues that are governed by the cell-autonomous circadian clock. However, mechanical stimulation has not yet directly been proven to modulate chondrogenesis via entraining the circadian clock in chondroprogenitor cells. The purpose of this study was to establish whether mechanical stimuli entrain the core clock in chondrogenic cells, and whether augmented chondrogenesis caused by mechanical loading was at least partially mediated by the synchronised, rhythmic expression of the core circadian clock genes, chondrogenic transcription factors, and cartilage matrix constituents at both transcript and protein levels. We report here, for the first time, that cyclic uniaxial mechanical load applied for 1 h for a period of 6 days entrains the molecular clockwork in chondroprogenitor cells during chondrogenesis in limb bud-derived micromass cultures. In addition to the several core clock genes and proteins, the chondrogenic markers SOX9 and ACAN also followed a robust sinusoidal rhythmic expression pattern. These rhythmic conditions significantly enhanced cartilage matrix production and upregulated marker gene expression. The observed chondrogenesis-promoting effect of the mechanical environment was at least partially attributable to its entraining effect on the molecular clockwork, as co-application of the small molecule clock modulator longdaysin attenuated the stimulatory effects of mechanical load. This study suggests that an optimal biomechanical environment enhances tissue homoeostasis and histogenesis during chondrogenesis at least partially through entraining the molecular clockwork.

Durability aspects of blended concrete systems subjected to combined mechanical and environmental loading using piezo sensor

• Durability of LC 3 and OPC concrete systems was investigated. • Comparison between combined and ideal chloride effect. • Equivalent structural parameter model was developed to identify the deterioration. • Deterioration of concrete under combined effect is less than ideal chloride effect. • LC 3 concrete system exhibits higher chloride resistance than OPC. In real-life structures, the structural elements are exposed to combined effect of mechanical load and environmental action simultaneously. So, monitoring these structures under combined effect is very crucial to understanding their behaviour under effect. This study compares and monitors the durability aspects of two different concrete systems namely ternary blended concrete and conventional concrete subjected to combined effect of chloride-induced corrosion and compression loading using piezo sensor based electro-mechanical impedance (EMI) technique. Experiments were conducted on two different types of concrete systems, one made with limestone calcined clay cement (LC 3 ) with 50 % by weight as a replacement to ordinary Portland cement (OPC), and the second made with OPC. Chloride penetration, chloride profiles, diffusion coefficient, and surface concentrations were the various parameters considered for the evaluation of durability performance. Further, an equivalent structural parameter (mass, stiffness, and damping) model has been proposed to identify the deterioration in these two concrete systems and an empirical relation has been established between equivalent stiffness and surface concentration for non-destructively monitoring. The results indicate that the percentage loss of equivalent stiffness in OPC concrete system under ideal chloride effect is 27 % more than combined effect, while in LC 3 concrete system it is 40 %. On comparing the deterioration of equivalent stiffness in OPC and LC 3 systems, it is found that in LC 3 concrete system the loss is 20 to 25 % less than that of OPC concrete system. Hence, it is concluded that the deterioration of concrete under the combined effect is significantly less than ideal chloride effect and LC 3 concrete system exhibits higher chloride resistance than the OPC concrete system.

Modelling on the synergy of mechanical and electrical wear in a current line/catenary-pantograph system

The metro system of electrified rolling stock is an important vehicle for partly solving the metropolitan transportation and carbon emission problems. This study aims to analyse the wear of current collector/catenary-pantograph system in the rolling stock. A theoretical wear rate model between the conductor wire and the current collector of the pantograph system was adopted from the literature and further decomposed into mechanical load, electrical current, current arc erosion, and the synergy components. Based on the decomposed model, an experimental protocol for finding the curve-fitted parameters for the theoretical model was proposed. The numerical data adopted from a previous literature was employed in the decomposed model to discuss the effects of mechanical loading, electrical current, and vehicle speed on the wear rate components. From the decomposed wear rate model, the so-called electrical current lubrication on the total wear rate due to the applied electrical current could be observed directly. Moreover, the nonlinear couplings among the control factors in the operation of the system manifested significantly. Thus, in the design phase the optimization analysis should be performed on the control parameters using the theoretical wear rate model to extend the life and reliability of this catenary-pantograph system.

Drug delivery carriers can alter cartilage biomechanics

Development of effective osteoarthritis (OA) therapeutics is challenged by difficulties in delivering drug molecules into articular cartilage, owing to the dense nature of cartilage extracellular matrix (ECM) and the fast clearance of drug molecules in the synovial joint ( 1 Bajpayee A.G. Grodzinsky A.J. Cartilage-targeting drug delivery: can electrostatic interactions help?. Nat. Rev. Rheumatol. 2017; 13: 183-193https://doi.org/10.1038/nrrheum.2016.210 Crossref PubMed Scopus (120) Google Scholar ). Cartilage ECM is characterized by a high negative fixed charge density, endowed by the proteoglycan, aggrecan, and its sulfated glycosaminoglycan (sGAG) side chains ( 2 Han L. Grodzinsky A.J. Ortiz C. Nanomechanics of the cartilage extracellular matrix. Annu. Rev. Mater. Res. 2011; 41: 133-168https://doi.org/10.1146/annurev-matsci-062910-100431 Crossref PubMed Scopus (135) Google Scholar ). Building on this knowledge, researchers have developed various cationic drug delivery carriers to promote drug penetration deep into cartilage, targeting chondrocytes throughout the whole tissue depth. A few examples include peptides ( 3 Vedadghavami A. Wagner E.K. Bajpayee A.G. et al. Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues. Acta Biomater. 2019; 93: 258-269https://doi.org/10.1016/j.actbio.2018.12.004 Crossref PubMed Scopus (41) Google Scholar ), proteins ( 4 DiDomenico C.D. Bonassar L.J. The effect of charge and mechanical loading on antibody diffusion through the articular surface of cartilage. J. Biomech. Eng. 2018; 141: 014502https://doi.org/10.1115/1.4041768 Crossref Scopus (4) Google Scholar ), synthetic polymers ( 5 Geiger B.C. Wang S. Hammond P.T. et al. Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis. Sci. Transl. Med. 2018; 10: eaat8800https://doi.org/10.1126/scitranslmed.aat8800 Crossref PubMed Scopus (121) Google Scholar ), and nanoparticles ( 6 Yan H. Duan X. Pham C.T.N. et al. Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc. Natl. Acad. Sci. USA. 2016; 113: E6199-E6208https://doi.org/10.1073/pnas.1608245113 Crossref PubMed Scopus (79) Google Scholar ). Effects of polycationic drug carriers on the electromechanical and swelling properties of cartilageWarren et al.Biophysical JournalJune 27, 2022In BriefCationic nanocarriers offer a promising solution to challenges in delivering drugs to negatively charged connective tissues, such as to articular cartilage for the treatment of osteoarthritis (OA). However, little is known about the effects that cationic macromolecules may have on the mechanical properties of cartilage at high interstitial concentrations. We utilized arginine-rich cationic peptide carriers (CPCs) with varying net charge (from +8 to +20) to investigate the biophysical mechanisms of nanocarrier-induced alterations to cartilage biomechanical properties. Full-Text PDF

Durability of Concrete under Combined Impact Environment and Mechanical Load: Analysis of Experimental Studies

Today, there are several methods for predicting the durability of reinforced concrete structures. In most cases, one of the dominant destruction processes is taken into account – either carbonization or chloride penetration. Experimental results and field observations show that this is an unrealistic approach. Therefore, it is necessary to develop a method for determining the durability of concrete under combined impacts, i. e. with the penetration of chlorides into it and mechanical load. The paper describes in detail an experimental method for studying the effect of mechanical load on the penetration of chlorides into the pore space of cement-based materials. A test method is presented that makes it possible to determine realistic diffusion coefficients of chloride ions in concrete under compressive or tensile stress. As a result of the experiments carried out, it has been determined that the combination of mechanical loads and environmental influences can be much more significant than just environmental influence without the influence of mechanical loading. In fact, the service life of reinforced concrete structures depends on many possible combinations of mechanical loads and environmental influences, including freeze-thaw cycles. Thus, cracks formed during freeze-thaw cycling should be taken into account in tests of combined environmental and mechanical stress in order to better understand and systematically describe the effect of such exposure on the durability of concrete. For reliable prediction of the service life of reinforced concrete structures, it is also necessary to take into account the influence of the applied cyclic stress.