Dynamic Mechanical Loading Research Articles

Deformation and Fracture Behavior of Alumina Particle-Reinforced Al 6061-T6 Composite during Dynamic Mechanical Loading

Alumina particle-reinforced aluminum 6061-T6 composites are subjected to deformation at high strain rates in torsion and in compression using Hopkinson bars. The volume content of alumina particles in the aluminum alloy are 10 and 20 pct. While occurrence of adiabatic shear bands is evident under compression, the specimens fractured rapidly in torsion at high strain rates. Fracture occurs in both testing modes by ductile shear failure with elongated dimples originating mostly from the particle matrix interface. Most of the reinforcing particles along the crack propagation path fractured in torsion. However, excessive thermal softening inside the shear bands in the specimens under compression loading caused debonding rather than fragmentation of most particles as the crack propagates along the shear bands.

The release of nickel from orthodontic NiTi wires is increased by dynamic mechanical loading but not constrained by surface nitridation

The influence of dynamic mechanical loading and of surface nitridation on the nickel release from superelastic nickel-titanium orthodontic wires was investigated under ultrapure conditions. Commercially available superelastic NiTi arch wires (size 0.018 x 0.025'') without surface modification (Neo Sentalloy) and with nitrogen ion implantation surface treatment (Neo Sentalloy Ionguard) were analyzed. Mechanical loading of wire segments with a force similar to the physiological situation was performed with a frequency of 5 Hz in ultrapure water and saline solution, respectively. The release of nickel was monitored by atomic absorption spectroscopy for up to 36 days. The mechanically loaded wires released significantly more nickel ( approximately 45 ng cm(-2) d(-1)) than did nonloaded wires (<1 ng cm(-2) d(-1)). There was no statistically significant effect of the testing solution (water or NaCl) or of the surface nitridation. The total amount of released nickel was small in all cases, but may nevertheless account for the occasional clinical observations of adverse reactions during application of NiTi-based orthodontic appliances. The surface nitridation did not constrain the release of nickel from NiTi under continuous mechanical stress.

Knee loading dynamically alters intramedullary pressure in mouse femora

Dynamic mechanical loads have been known to stimulate bone formation. Many biophysical factors such as number of daily loading cycles, bone strain, strain-induced interstitial fluid flow, molecular transport, and modulation of intramedullary pressure have been considered as potential mediators in mechanotransduction of bone. Using a knee loading modality that enhances anabolic responses in mouse hindlimb, we addressed a question: Do oscillatory loads applied to the knee induce dynamic alteration of intramedullary pressure in the femoral medullary cavity? To answer this question, mechanical loads were applied to the knee with a custom-made piezoelectric loader and intramedullary pressure in the femoral medullary cavity was measured with a fiber optic pressure sensor. We observed that in response to sinusoidal forces of 0.5 Hz and 10 Hz, pressure amplitude increased up to 4-N loads and reached a plateau at 130 Pa. This amplitude significantly decreased with a loading frequency above 20 Hz. To confirm alteration of intramedullary pressure, real-time motion of microparticles in a glass tube inserted to the femoral medullary cavity ex vivo was visualized. Taken together, these data reveal that knee loading dynamically alters intramedullary pressure as a function of loading intensities and frequencies.

Regulation of Cartilaginous ECM Gene Transcription by Chondrocytes and MSCs in 3D Culture in Response to Dynamic Loading

This study explored the biologic response of chondrocytes and mesenchymal stem cells (MSCs) to a dynamic mechanical loading regime. We developed a time-efficient methodology for monitoring regional changes in extracellular matrix gene transcription using reporter promoter constructs. Specifically, transfected cells were homogenously distributed throughout agarose hydrogel constructs, and spatial and temporal gene expression and the ability to form functional ECM were analyzed in response to dynamic mechanical stimuli. Theoretical analyses were used to predict the physical signals generated within the gel in response to these loading regimes. Using a custom compression bioreactor system, changes in aggrecan and type II collagen promoter activity in transfected chondrocyte-laden cylindrical constructs were evaluated in response to a range of loading frequencies and durations. In general, aggrecan promoter activity increased with increasing duration of loading, particularly in the outer annulus region. Interestingly, type II collagen promoter activity decreased in this annular region under identical loading conditions. In addition, we explored the role of mechanical compression in directing chondrogenic differentiation of MSCs by monitoring short-term aggrecan promoter activity. As an example of long-term utility, a specific loading protocol was applied to MSC-laden constructs for 5 days, and the resultant changes in glycosaminoglycan (GAG) production were evaluated over a 4-week period. This dynamic loading regime increased not only short-term aggrecan transcriptional activity but also GAG deposition in long-term culture. These results demonstrate the utility of a new reporter promoter system for optimizing loading protocols to improve the outcome of engineered chondrocyte- and MSC-laden cartilaginous constructs.

Spectral Analysis of Impact Accelerations Using Bone Versus Surface Mounted Accelerometers

The heel-strike transient, during running, results in an impact acceleration that gets propagated up the musculoskeletal system. Depending on its magnitude, rate, and frequency the acceleration may have positive or negative physiological effects. Traditionally, impact acceleration has been measured by skin-mounted accelerometers fixed to the distal anteriomedial tibia. Previous research using accelerometers attached to pins inserted in bone suggested that skin-mounted accelerometers may overestimate impact acceleration by 8 to 50%. PURPOSE: To determine if skin-mounted accelerometers result in attenuation or gain in impact acceleration when compared to bone-mounted accelerometers. METHODS: Two human cadaver lower extremities were mounted via an intra-medullary rod to a dynamic gait simulator. Ankle angle was controlled prior to impact by applying tension to the anterior tibialis muscle. Two uniaxial accelerometers were attached to the distal anteriomedial tibia, one directly to the bone and another to the skin. A Fast Fourier Transformation was used to determine the power spectra of the impact phase accelerations for 24 trials. The power spectral densities (PSD) of the bone-mounted accelerometer (BA) and skin-mounted accelerometer (SA) were used to calculate transfer functions for impact frequencies between 15 and 25 Hz. The overall transfer was calculated as the average transfer for the impact frequencies. Effect size was also calculated to determine the strength of difference between the average PSDs of the BA and SA for the impact frequencies. RESULTS: The dynamic gait simulator produced peak impact accelerations equivocal to those observed during normal walking/running ranging from 1.6 to 5.3 g. Peak impact acceleration for BA was 0.5 ± 0.4 g larger than SA and the transfer functions revealed that the SA impact attenuation was −1.9 dB. Effect size for average PSDs was −0.56 indicating a moderate difference between BA and SA. CONCLUSION: Although an overall impact attenuation was found in SA, the difference is small. If dynamic mechanical loading on bone is an underlying mechanism in bone adaptation, these preliminary results suggest that SAs may be a good predictor of skeletal impact acceleration. Future research will look to increase sample size as well as peak impact accelerations to see if this relationship can be applied to all subjects and impact accelerations typically seen at faster running velocities.

In Vitro Tendon Engineering with Avian Tenocytes and Polyglycolic Acids: A Preliminary Report

Although there are many reports of in vivo tendon engineering using different animal models, only a few studies involve the short-term investigation of in vitro tendon engineering. Our previous study demonstrated that functional tendon tissue could be engineered in vivo in a hen model using tenocytes and polyglycolic acid (PGA) fibers. This current study explored the feasibility of in vitro tendon engineering using the same type of cells and scaffold material. Tenocytes were extracted from the tendons of a hen's foot with enzyme digestion and cultured in DMEM plus 10% FBS. Unwoven PGA fibers were arranged into a cord-like construct and fixed on a U-shape spring, and tenocytes were then seeded on PGA fibers to generate a cell-PGA construct. In experimental group 1, 22 cell-scaffold constructs were fixed on the spring with no tension and collected at weeks 4 (n = 7), 6 (n = 7) and 10 (n = 8); in experimental group 2, five cell-scaffold constructs were fixed on the spring with a constant strain and collected after 6 weeks of culture. In the control group, three cell-free scaffolds were fixed on the spring without tension. The collected engineered tendons were subjected to gross and histological examinations and biomechanical analysis. The results showed that tendon tissue could be generated during in vitro culture. In addition, the tissue structure and mechanical property became more mature and stronger with the increase of culture time. Furthermore, application of constant strain could enhance tissue maturation and improve mechanical property of the in vitro engineered tendon (1.302 +/- 0.404 Mpa with tension vs 0.406 +/- 0.030 Mpa without tension at 6 weeks). Nevertheless, tendon engineered with constant strain appeared much thinner in its diameter than tendon engineered without mechanical loading. Additionally, its collagen fibers were highly compacted when compared to natural tendon structure, suggesting that constant strain may not be the optimal means of mechanical load. Thus, application of dynamic mechanical load with a bioreactor to the construction of tendon tissue will be our next goal in this series of in vitro tendon engineering study.

Migration of two different cementless hip arthroplasty stems in combination with two different heads: a biomechanical in vitro study

The aim of the present in vitro study was to evaluate migrational characteristics of cementless primary hip arthroplasty stems in combination with a diameter 50 mm head (hemiarthroplasty) and a diameter 28 mm head in and with a polyethylene cup (total hip arthroplasty) in fresh-frozen human specimens. Two different types (Endo SL, FMT) were implanted into seven pairs of fresh-frozen human femoral specimens. The implanted stems were combined with a diameter 50 mm head (hemiarthroplasty) on one side and with a polyethylene cup and a 28 mm head (total hip arthroplasty) on the other side. Dynamic mechanical loading was applied for 50,000 cycles while recording relative motions between stem and bone stock using a 3-D motion analysis system. The Endo SL stem showed a significantly higher amplitude of relative motion in all translational and rotational components regardless of the head used. In both stem types a strong tendency for higher axial migration with the diameter 50 mm head in comparison to the THA head was found. The lowest axial migration was found in the FMTstem in combination with the small head and a PE cup. The highest axial migration was found in the Endo SL stem combined with the diameter 50 mm head. Our results indicate that the head might play an important role for axial migration of cementless stems.

Impact of sarcoglycan complex on mechanical signal transduction in murine skeletal muscle

Loss of the dystrophin glycoprotein complex (DGC) or a subset of its components can lead to muscular dystrophy. However, the patterns of symptoms differ depending on which proteins are affected. Absence of dystrophin leads to loss of the entire DGC and is associated with susceptibility to contractile injury. In contrast, muscles lacking gamma-sarcoglycan (gamma-SG) display little mechanical fragility and still develop severe pathology. Animals lacking dystrophin or gamma-SG were used to identify DGC components critical for sensing dynamic mechanical load. Extensor digitorum longus muscles from 7-wk-old normal (C57), dystrophin- null (mdx), and gamma-SG-null (gsg(-/-)) mice were subjected to a series of eccentric contractions, after which ERK1/2 phosphorylation levels were determined. At rest, both dystrophic strains had significantly higher ERK1 phosphorylation, and gsg(-/-) muscle also had heightened ERK2 phosphorylation compared with wild-type controls. Eccentric contractions produced a significant and transient increase in ERK1/2 phosphorylation in normal muscle, whereas the mdx strain displayed no significant proportional change of ERK1/2 phosphorylation after eccentric contraction. Muscles from gsg(-/-) mice had no significant increase in ERK1 phosphorylation; however, ERK2 phosphorylation was more robust than in C57 controls. The reduction in mechanically induced ERK1 phosphorylation in gsg(-/-) muscle was not dependent on age or severity of phenotype, because muscle from both young and old (age 20 wk) animals exhibited a reduced response. Immunoprecipitation experiments revealed that gamma-SG was phosphorylated in normal muscle after eccentric contractions, indicating that members of the DGC are modified in response to mechanical perturbation. This study provides evidence that the SGs are involved in the transduction of mechanical information in skeletal muscle, potentially unique from the entire DGC.

Regulation of RANKL by biomechanical loading in fibrochondrocytes of meniscus

Objective We sought to determine whether fibrochondrocytes from menisci express receptor activator of NF- κB (RANK), its ligand (RANKL), or osteoprotegerin (OPG) and, if so, whether their expression is modulated by dynamic mechanical loading under inflammatory and normal conditions. Methods Fibrochondrocytes from rat menisci were subjected to cyclic tensile strain (CTS) at various magnitudes and frequencies in the presence or absence of interleukin (IL)-1 β for up to 24 h. In order to determine whether a possible regulatory effect of mechanical loading on RANKL and its receptors under inflamed conditions is sustained, cells were stimulated with IL-1 β for 24 h while being subjected to CTS only for the initial 4 and 8 h, respectively. Regulation of RANKL, RANK, and OPG expression and synthesis were determined by semiquantitative and real-time PCR, Western blotting, and immunofluorescence. Result Fibrochondrocytes constitutively expressed low levels of RANKL and RANK but marked levels of OPG. IL-1 β upregulated expression and synthesis of RANKL and RANK significantly ( p < 0.05 ), whereas expression of OPG was unaffected following 4 and 24 h. When fibrochondrocytes were simultaneously subjected to CTS and IL-1 β, expression of RANKL and RANK was significantly ( p < 0.05 ) downregulated as compared to that of IL-1 β-stimulated unstretched cells. The inhibitory effect of CTS on the IL-1 β-induced upregulation of RANKL and RANK was sustained as well as magnitude and frequency dependent. Conclusions Our study provides evidence that RANKL and its receptors are expressed in fibrochondrocytes from meniscus. These data also demonstrate that dynamic mechanical loading can modify the expression of RANKL and RANK in inflammatory conditions.

A cartilage growth mixture model for infinitesimal strains: solutions of boundary-value problems related to in vitro growth experiments

A cartilage growth mixture (CGM) model is linearized for infinitesimal elastic and growth strains. Parametric studies for equilibrium and nonequilibrium boundary-value problems representing the in vitro growth of cylindrical cartilage constructs are solved. The results show that the CGM model is capable of describing the main biomechanical features of cartilage growth. The solutions to the equilibrium problems reveal that tissue composition, constituent pre-stresses, and geometry depend on collagen remodeling activity, growth symmetry, and differential growth. Also, nonhomogeneous growth leads to nonhomogeneous tissue composition and constituent pre-stresses. The solution to the nonequilibrium problem reveals that the tissue is nearly in equilibrium at all time points. The results suggest that the CGM model may be used in the design of tissue engineered cartilage constructs for the repair of cartilage defects; for example, to predict how dynamic mechanical loading affects the development of nonuniform properties during in vitro growth. Furthermore, the results lay the foundation for future analyses with nonlinear models that are needed to develop realistic models of cartilage growth.

Extracellular nucleotides activate Runx2 in the osteoblast-like HOBIT cell line: a possible molecular link between mechanical stress and osteoblasts' response

Dynamic mechanical loading increases bone density and strength and promotes osteoblast proliferation, differentiation and matrix production, by acting at the gene expression level. Molecular mechanisms through which mechanical forces are conversed into biochemical signalling in bone are still poorly understood. A growing body of evidence point to extracellular nucleotides (i.e., ATP and UTP) as soluble factors released in response to mechanical stimulation in different cell systems. Runx2, a fundamental transcription factor involved in controlling osteoblasts differentiation, has been recently identified as a target of mechanical signals in osteoblastic cells. We tested the hypothesis that these extracellular nucleotides could be able to activate Runx2 in the human osteoblastic HOBIT cell line. We found that ATP and UTP treatments, as well as hypotonic stress, promote a significant stimulation of Runx2 DNA-binding activity via a mechanism involving PKC and distinct mitogen-activated protein kinase cascades. In fact, by using the specific inhibitors SB203580 (specific for p38 MAPK) and PD98059 (specific for ERK-1/2 MAPK), we found that ERK-1/2, but not p38, play a major role in Runx2 activation. On the contrary, another important transcription factor, i.e., Egr-1, that we previously demonstrated being activated by extracellular released nucleotides in this osteoblastic cell line, demonstrated to be susceptible to both ERK-1/2 and p38 kinases. These data suggest a possible differential involvement of these two transcription factors in response to extracellularly released nucleotides. The biological relevance of our data is strengthened by the finding that a target gene of Runx2, i.e., Galectin-3, is up-regulated by ATP stimulation of HOBIT cells with a comparable kinetic of that found for Runx2. Since it is known that osteocytes are the primary mechanosensory cells of the bone, we hypothesize that they may signal mechanical loading to osteoblasts through release of extracellular nucleotides. Altogether, these data suggest a molecular mechanism explaining the purinoreceptors-mediated activation of specific gene expression in osteoblasts and could be of help in setting up new pharmacological strategies for the intervention in bone loss pathologies.

Relating Local Bone Stiffness and Calcium Content by Combined Nanoindentation and Backscattered Electron Imaging

AbstractBone is a hierarchically structured mineral-organic composite material that has to bear static and dynamic mechanical loads applied by body weight and locomotion. Bone mechanical properties are influenced by a number of factors, depending on the particular hierarchical levels. The high stiffness of bone material is mainly achieved by reinforcement with calcium phosphate mineral platelets. A model for this elementary structure level consists of an arrangement of staggered mineral bricks, embedded in collagen matrix, which provides both stiffness and toughness. The mechanical properties depend on the amount, shape and arrangement of the mineral particles but also on the properties of the collagen-rich matrix.One of the difficulties in assessing the properties of hierarchical structures is the inherent inhomogeneity of the tissue: Parameters such as stiffness or calcium content vary throughout a bone section. Such type of investigations becomes more meaningful by a combination of two complementary methods e.g. quantitative backscattered electron imaging (qBEI) and nanoindentation. The local Ca-content, representing the degree of the mineralization, is extracted from the qBEI measurements, whereas the local mechanical properties, elastic modulus and hardness, are measured by nanoindentation, a miniaturized hardness testing using a small diamond tip. The measured correlations between local Ca-content and mechanical strength help, for example, to verify biomechanical models based on the nanocomposite structure of bone. They may also shed new light on bone diseases such as osteoporosis or osteogenesis imperfecta.

Modeling of a circular plate with piezoelectric actuators

This paper presents an analytical approach for modeling of circular plate containing distributed piezoelectric actuators under static as well as dynamic mechanical or electrical loadings. The analytical approach used in this paper is based on the Kirchhoff plate model. The equations governing the dynamics of the plate, relating the strains in the piezoelectric elements to the strain induced in the system, are derived for circular plate using the partial differential equation. The natural frequencies and mode shapes of the structures were determined by modal analysis. In addition, the harmonic analysis is performed for analyzing the steady-state behavior of the structures subjected to cyclic sinusoidal loads. Numerical simulation results are obtained using finite element approach. Experiments using a thin circular aluminum plate structure with distributed piezoelectric actuators were also conducted to verify the analysis and the computer simulations. Relatively good agreements between the results of these three approaches are observed. Finally, the results show that the model can predict natural frequencies and modes shapes of the plate very accurately.

Wide Band Tunable Mechanical Resonator Employing the ΔE Effect of Terfenol-D

The control of Terfenol-D’s operational elastic modulus offers opportunities for novel devices and applications capitalizing on real-time changes in material stiffness. This work describes the development and testing of a Terfenol-D transducer employed as a wide-band variable frequency mechanical resonator. The design and construction of such a wide-band mechanical resonator for testing under controlled thermal, magnetic and dynamic mechanical load conditions are described. Changes in Terfenol-D’s elastic modulus, the ΔE effect, approaching 266% are demonstrated in the mechanical resonator utilizing a range of d.c. applied magnetic field levels of less than 61.0 kA/m. The elastic modulus and damping characteristics of Terfenol-D, critical to the successful design of devices employing the ΔE effect, are examined.

Effects of dynamic compressive loading on chondrocyte biosynthesis in self-assembling peptide scaffolds

Dynamic mechanical loading has been reported to affect chondrocyte biosynthesis in both cartilage explant and chondrocyte-seeded constructs. In this study, the effects of dynamic compression on chondrocyte-seeded peptide hydrogels were analyzed for extracellular matrix synthesis and retention over long-term culture. Initial studies were conducted with chondrocyte-seeded agarose hydrogels to explore the effects of various non-continuous loading protocols on chondrocyte biosynthesis. An optimized alternate day loading protocol was identified that increased proteoglycan (PG) synthesis over control cultures maintained in free-swelling conditions. When applied to chondrocyte-seeded peptide hydrogels, alternate day loading stimulated PG synthesis up to two-fold higher than that in free-swelling cultures. While dynamic compression also increased PG loss to the medium throughout the 39-day time course, total PG accumulation in the scaffold was significantly higher than in controls after 16 and 39 days of loading, resulting in an increase in the equilibrium and dynamic compressive stiffness of the constructs. Viable cell densities of dynamically compressed cultures differed from free-swelling controls by less than 20%, demonstrating that changes in PG synthesis were due to an increase in the average biosynthesis per viable cell. Protein synthesis was not greatly affected by loading, demonstrating that dynamic compression differentially regulated the synthesis of PGs. Taken together, these results demonstrate the potential of dynamic compression for stimulating PG synthesis and accumulation for applications to in vitro culture of tissue engineered constructs prior to implantation.

A multi-station dynamic-culture force monitor system to study cell mechanobiology

To study mechanobiological responses of cells, a dynamic-culture force monitor (D-CFM) system has been developed. The D-CFM extends our previous work to measure contractile forces of a cell-populated collagen gel (CPCG) using a cantilever beam with semiconductor strain gauges. Linear actuators are used in the system and are computer controlled using a LabVIEW interface to independently apply precise motion waveforms to multiple CPCGs. The feasibility tests showed that the new system can detect the differences in force patterns resulting from different motion waveforms imparted to the CPCG. This new system will facilitate the study of the effects of dynamic mechanical loading on cells, remodeling of extracellular matrix, and cell–matrix interactions in vitro.

Acousto-optical Characterization of the Viscoelastic Nature of a Nuchal Elastin Tissue Scaffold

A nondestructive, acousto-optical method for characterizing the mechanical loss factor of biological tissues and tissue scaffolds is presented and applied to the characterization of an elastin tissue scaffold derived from bovine nuchal ligament. The method relies on launching guided surface acoustic waves into the tissue scaffold with a small speaker and simultaneously illuminating a small region of the scaffold distant from the speaker with a low-power HeNe laser. The phase lag between the driving acoustic wave and the shift in the backscattered laser speckle pattern is determined as a measure of the mechanical loss factor of the scaffold, tan delta. Measurements of tan delta and elastic modulus were also made by traditional dynamic mechanical loading techniques. Through the central portion of the loading cycle, the elastic modulus of the elastin scaffold was 1.2 x 10(6) +/- 1 x 10(5) N x m(-2) (parallel to fiber orientation). The estimated value of tan delta in the direction parallel to the elastin fibers was 0.03 +/- 0.017 by traditional methods and 0.029 +/- 0.03 when using the acousto-optical method. In the direction perpendicular to fiber orientation, tan delta was measured as 0.14 +/- 0.056 by the acousto-optical method. Because of a lack of mechanical integrity, it was not possible to measure tan delta in the direction perpendicular to fiber orientation by traditional methods. The acousto-optical method may prove to be useful in the mechanical characterization of developing engineered tissues.

Mapping liquid distribution in absorbent incontinence products.

This paper reviews methods available for mapping the distribution of fluid in incontinence pad materials to assist with evaluating existing products and developing new ones, and to provide data for building and validating predictive models. Specifically, the following technologies are considered and their strengths and limitations described: discrete sensors based on conductance, temperature or optical measurements, optical imaging, gravimetric methods, X-ray imaging and magnetic resonance imaging. It is suggested that the ideal method would enable fluid distribution to be mapped in three dimensions with good spatial and time resolution in single materials and composite structures of simple and complex geometries under static and dynamic mechanical loading. It would also allow liquid to be mapped in products when worn by users. It is concluded that, although each existing method meets some of these requirements, and each requirement is met, at least reasonably well, by at least one method, improved techniques are needed. The particular need for methods that can provide some measurement of liquid saturation within absorbent products, both in the laboratory and in real use, is highlighted. In many cases, simple methods used appropriately are sufficient to elicit the important aspects of liquid transport and storage within absorbent products.

New insight into deformation-dependent hydraulic permeability of gels and cartilage, and dynamic behavior of agarose gels in confined compression

Equilibrium, creep, and dynamic behaviors of agarose gels (2.0–14.8%) in confined compression were investigated in this study. The hydraulic permeabilities of gels were determined by curve-fitting creep data to the biphasic model (J. Biomech. Eng. 102 (1980) 73) and found to be similar in value to those published in the literature (AIChE J. 42 (1996) 1220). A new relationship between intrinsic permeability and volume fraction of water was found for agarose gel, capable of predicting deformation-dependent permeabilities of bovine articular cartilage and 2% agarose gel published in literature. This relationship is accurate for gels and cartilage over a wide range of permeabilities (four orders of magnitude variation). The dynamic stiffness of the gels increases with gel concentration and loading frequency (0.01–1.0 Hz). The increase in dynamic stiffness with loading frequency is less pronounced for gels with higher concentrations. The results of this study provide a new insight into deformation-dependent permeability behavior of agarose gel and cartilage, and are important for understanding biological responses of cells to interstitial fluid flow in gel or in cartilage under dynamic mechanical loading.

Rapid regulation of collagen but not metalloproteinase 1, 3, 13, 14 and tissue inhibitor of metalloproteinase 1, 2, 3 expression in response to mechanical loading of cartilage explants in vitro

This study analyzes the molecular response of articular chondrocytes to short-term mechanical loading with a special focus on gene expression of molecules relevant for matrix turnover. Porcine cartilage explants were exposed to static and dynamic unconfined compression and viability of chondrocytes was assessed to define physiologic loading conditions. Cell death in the superficial layer correlated with mechanical loading and occurred at peak stresses ⩾6 MPa and a cartilage compression above 45%. Chondrocytes in native cartilage matrix responded to dynamic loading by rapid and highly specific suppression of collagen expression. mRNA levels dropped 11-fold (collagen 2; 6 MPa, P=0.009) or 14-fold (collagen 1; 3 and 6 MPa, P=0.009) while levels of aggrecan, tenascin-c, matrix metalloproteinases (MMP1, 3, 13, 14), and their inhibitors (TIMP1-3) did not change significantly. Thus, dynamic mechanical loading rapidly shifted the balance between collagen and aggrecan/tenascin/MMP/TIMP expression. A better knowledge of the chondrocyte response to mechanical stress may improve our understanding of mechanically induced osteoarthrits.