Continuous Mechanical Loading Research Articles

Osteopontin Upregulation, Induced by the Continuous Mechanical Load in Adipose Tissue-Derived Mesenchymal Stem Cells, is Strongly Restricted in INF-γ/TNF-α/IL-22 Microenvironment.

The osteogenic potential of mesenchymal stem cells (MSc) in axial spondyloarthritis (AxSpA) depends on the interplay of inflammation and multiple hormonal and local mechanical factors. In this study, MCs, derived from the adipose tissue of a healthy donor, were cultured under or without continuous mechanical load in the osteogenic differentiation medium with or without the addition of testosterone, cocktail of INF-γ/TNF-α/IL-22, or both. Real-time PCR for osteogenic transcription factors demonstrated that in the absence of INF-γ/TNF-α/IL-22, mechanical load causes significant upregulation of SPP1 (osteopontin), while the presence of the inflammatory cytokines almost completely abolishes this effect. In addition, exposure to INF-γ/TNF-α/IL-22 slightly upregulated BMP2, but suppressed the expression of ALPL, Col1A1, and SPP1, reinforcing the hypothesis that the inflammatory environment allows MSc to commit toward the IL-22-driven osteogenic differentiation butcan restrict the later stages of osteogenesis. In summary, osteopontin can play a role in the pathogenesis of AxSpA, linking between mechanical load and pathological bone formation.

In-situ coupled mechanical/electrical investigations on conductive TPU/CB composites: Impact of thermo-mechanically induced structural reorganizations of soft and hard TPU domains on the coupled electro-mechanical properties

In-situ coupled mechanical/electrical investigations on TPU-based nanocomposite materials filled with carbon black have been carried-out under continuous and cyclic mechanical loading, with simultaneous measurements of stress, strain and electrical conductivity as function of the strain rate and amplitude. The impact of mechanical deformation and thermal treatment on the structure/properties relationship has been investigated by employing SAXS/WAXS, DSC and TEM measurements. Higher conduction properties were through dynamic percolation induced by TPU soft domains crystallization. The TPU hard domains were found to be more sensitive to thermal treatment: annealing at high temperature led to microcrystalline hard domains that strongly influenced the conductivity evolution upon mechanical deformation. Structural and morphological reorganizations induced by mechanical deformation and thermal treatment can be thus efficiently used to adjust the coupled electro-mechanical behavior of TPU-based composite materials.

Antifungal Effect of Piezoelectric Charges on PMMA Dentures.

Candida-associated denture stomatitis is a recurring disease affecting up to 67% of denture wearers. Poly(methyl methacrylate) (PMMA) remains the main material employed in the fabrication of dentures due to its desirable physical, mechanical, and aesthetic properties. However, the improvement of its antimicrobial properties remains a challenge. To address this need, we developed PMMA composite filled with piezoelectric nanoparticles of barium titanate (BaTiO3) for therapeutic effects. Candida albicans biofilms were cultivated on the surface of the composites under continuous cyclic mechanical loading to activate the piezoelectric charges and to resemble mastication patterns. The interactions between biofilms and biomaterials were evaluated by measuring the biofilm biomass, metabolic activity, and the number of viable cells. To explore the antifungal mechanisms, changes in the expression of genes encoding adhesins and superoxide dismutase were assessed using reverse transcription-polymerase chain reaction. With the addition of piezoelectric nanoparticles, we observed a significant reduction in the biofilm formation and interference in the yeast-to-hyphae transition compared to the standard PMMA. Moreover, we observed that the cyclic deformation of biomaterial surfaces without antifungal agents produced increased biomass, metabolic activity, and a number of viable cells compared to the static/no-deformed surfaces. Cyclic deformation appears to be a novel mechanobiological signal that enables pathogenicity and virulence of C. albicans cells with increased expression of the yeast-to-hyphae transition genes. The outcome of this study opens new opportunities for the design of antifungal dentures for improved clinical service and reduced need for cleaning methods.

The Effect of Rod Pattern, Outrigger, and Multiple Screw-Rod Constructs for Surgical Stabilization of the 3-Column Destabilized Cervical Spine - A Biomechanical Analysis and Introduction of a Novel Technique.

ObjectiveAnterior-only reconstructions for cervical multilevel corpectomies are prone to fail under continuous mechanical loading. This study sought to define the mechanical characteristics of different constructs in reducing a range of motion (ROM) of the 3-column destabilized cervical spine, including posterior cobalt-chromium (CoCr)-rods, outrigger-rods (OGR), and a novel triple rod construct using lamina screws (6S3R). The clinical implications of biomechanical findings are discussed in depth from the perspective of the challenges surgeons face cervical deformity correction. MethodsThree-column deficient cervical spinal models were produced based on reconstructed computed tomography scans. The corpectomy defect between C3 and C7 end-level vertebrae was restored with anterior titanium (Ti) mesh-cage. The ROM was evaluated in a customized 6-degree of freedom spine tester. Tests were performed with different rod materials (Ti vs. CoCr), varying diameter rods (3.5 mm vs. 4.0 mm), with and without anterior plating, and using different construct patterns: bilateral rod fixation (standard-group), OGR-group, and 6S3R-Group. Construct stability was expressed in changes and differences of ROM (°). ResultsThe largest reduction of ROM was noticed in the 6S3R-group compared to the standard- and the OGR-group. All differences observed were emphasized with an increasing number of corpectomy levels and if anterior plating was not added. For all simulated 1-, 2-, and 3-level corpectomy constructs, the OGR-group revealed decreased ROM for all motion directions compared to the standard-group. An increase of construct stiffness was also recorded for increased rod diameter (4.0 mm) and stiffer rod material (CoCr), though these effects lacked behind the more advanced construct pattern. ConclusionA novel reconstructive technique, the 6S3R-construct, was shown to outperform all other constructs and might resemble a new standard of reference for advanced posterior fixation.

Saving energy on meat air convection drying with pulsed electric field coupled to mechanical press water removal

The present study analyses the effects of low intensity pulsed electric fields (PEFs), coupled to mechanical press dewatering on meat drying with air convection. Process parameter optimization using Taguchi design showed that the number of pulses had most significant effect on meat dewatering. A maximum effective diffusivity of 2.31 × 10−9 m2 s−1 was observed for PEF assisted drying of chicken meat at 80 °C. An overall energy saving of 933.18 ± 22 J g−1 was observed for drying at 60 °C when the meat was treated with a voltage of 75 V with initial distance between electrodes of 6.917 ± 0.38 mm, pulse length 7 ms, 300 pulses with a frequency of 2 Hz under 125.44 kPa continuous mechanical load. Our study suggests that PEF coupled to mechanical dewatering saves energy in conventional meat drying with air convection. Such a strategy could provide a scalable model for PEF assisted drying of various food products with higher energy efficiency and improved diffusivity.

Abstract 3481: Continuous load bearing exercise inhibits the development of prostate cancer bone metastasis

Abstract Background: Prostate cancer (PCa) preferentially metastasizes to bone, causing considerable mortality and morbidity. Exercise is a widely accepted intervention for improving bone health and can benefit overall health in patients with PCa. However, there are no direct studies defining the impact of various exercise regimens on the development of PCa bone metastasis. Hypothesis: Exercise regimens that induce osteogenic responses inhibit the growth of PCa cells in bone. Methods: Human PCa cells (PC3, 1x105 cells per injection) were intracardiacally injected into 8-week-old male BALB/c nude mice which were then subjected to right tibial dynamic mechanical loading (mimicking load bearing exercise, 9N peak force, 40 cycles with 10 second intervals, three times a week) or treadmill exercise (12 meters/minute, 30 minutes/day, 5 days/week) for 3 weeks. Another cohort of mice were firstly subjected to one week of mechanical loading before the inoculation of PC3 cells and then withdrawn from exercise regimen. The growth of skeletal tumours was tracked by bioluminescence for 3 weeks post-injection and bone structure was examined by micro-CT ex vivo. For mechanical loading experiments, comparison was made between loaded and contra-lateral non-loaded tibias, while treadmill exercise group was compared to sedentary controls in the treadmill study. Results: In the continuous mechanical loading group, tumours were detected in non-loaded tibias in all 12 mice (100%), whilst 8 out of 12 mice showed reduced skeletal tumours in the loaded tibias (67%), with 4 having no tumour in the loaded leg (33%). Tumour burden (Flux: photon/second) in the non-loaded tibias was 134% higher than that in the loaded tibias. Micro-CT analysis suggested that loaded tibias had significantly increased trabecular (BV/TV) and cortical bone volume and trabecular thickness (Tb.Th) (p<0.001). Surprisingly, treadmill exercised mice had higher tumour burden (~91%) in the hind limbs compared to the sedentary controls (P<0.05), with no statistically significant improvement in bone mass examined by micro-CT. In the loading withdrawal group, 6 out of 8 mice (75%) showed larger tumour size in the loading withdrawal tibias than in the non-loaded tibias, while only two mice (25%) had smaller or no tumour in the loading withdrawal tibias. Tumor burden were ~90% higher in the loading withdrawal tibias (p<0.05, t-test). This is associated with fast diminishing osteogenic response within a week after ceasing the loading stimulus, confirmed using micro-CT analysis by comparing percentage changes of BV/TV and Tb.Th among baseline, 1-week loading, and loading withdrawn groups. Conclusion: The continuity of high-intensity load bearing exercise is critical to prevent PCa growth in bone, possibly via maintaining the balance of bone remodelling towards osteoblastic bone formation. Mild aerobic exercise evaluated here was unable to significantly improve bone mass or achieve the benefits in inhibiting PCa bone metastases observed with high intensity loading. Citation Format: Ning Wang, Hector M. Arredondo, Alexandria R. Sprules, Colby L. Eaton. Continuous load bearing exercise inhibits the development of prostate cancer bone metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3481.

A 12-month continuous and intermittent high-impact exercise intervention and its effects on bone mineral density in early postmenopausal women: a feasibility randomized controlled trial.

Intermittent mechanical loading generates greater bone adaptations than continuous mechanical loading in rodents but has never been evaluated in humans. This study aimed to evaluate the feasibility of a continuous and intermittent countermovement jump (CMJ) intervention for attenuating early postmenopausal BMD loss. 41 healthy early postmenopausal women (age=54.6±3.4 years) were randomly assigned to a continuous countermovement jumping group, an intermittent countermovement jumping group or a control group for 12 months. Adherence and dropout rates were recorded along with bone mineral density (BMD) at lumbar spine, femoral neck and trochanter sites at baseline, 6 months and 12 months. 28 participants completed the study. Dropout rate during the intervention (from the initiation of exercise) was 36% from continuous and 38% from intermittent countermovement jumping groups. For the participants that completed the intervention, adherence was 60.0±46.8% for continuous and 68.5±32.3% for intermittent countermovement jumping. The control group lost significant lumbar spine BMD (% difference=-2.7 [95%CI: -3.9 to -1.4]) and femoral neck BMD (% difference=-3.0% [95%CI: -5.1 to -0.8]). There was no statistically significant change in BMD for either countermovement jumping group. There was no statistically significant difference in BMD change between continuous or intermittent countermovement jumping groups when compared with the control group. Adherence and dropout rates were in line with previous similar interventions. To evaluate the effect of continuous and intermittent exercise on BMD, future studies should focus on maintaining participant engagement and adherence to the exercise intervention.

The expression of anaerobic metabolites in sweat and sebum from human skin subjected to intermittent and continuous mechanical loading

Pressure ulcers (PUs) represent a substantial burden to both patients and healthcare providers. Accordingly, effective prevention strategies should follow early detection of PUs. Anaerobic metabolites, such as lactate and pyruvate, are promising noninvasive biomarkers indicative of tissue ischaemia, one of the major mechanisms leading to PU development. The aim of this study was to investigate if the temporal release profile of these metabolites in sweat and sebum is sensitive to detect local tissue changes resulting from prolonged mechanical loads.The sacrum of healthy volunteers was subjected to two different loading protocols. After a baseline measurement, the left and right side of the sacrum were subjected to continuous and intermittent loading regimen, respectively, at a pressure of 100 mmHg. Biomarker samples were collected every 20 min, with a total experimental time of 140 min. Sweat was collected at 37 ∘C and 80% relative humidity, and sebum at ambient conditions, from 11 to 13 volunteers, respectively. Both samples were analysed for lactate and pyruvate concentrations using ultra-high performance supercritical fluid chromatography mass spectrometry. Prior to analysis metabolite concentrations were normalized to individual baseline levels and, in the case of sweat, additional normalization was performed to an unloaded control site to account for fatigue of sweat glands.Although substantial variability was present, the temporal release profiles of both sweat and sebum metabolites reflected the applied loading regimen with increased levels upon load application, and recovery to baseline levels following load removal. Highest relative increases were 20% and 30% for sweat lactate and pyruvate, respectively, and 41% for sebum lactate. Sebum pyruvate was not present in quantifiable amounts. There was a linear correlation between the individual responses to intermittent and continuous loading.The present study revealed that metabolite biomarkers in both sweat and sebum were sensitive to the application of mechanical loads, indicative of local ischaemia within skin and soft tissues. Similar trends in metabolic biomarkers were observed in response to intermittent and continuous loading regimens in both sweat and sebum. Metabolites represent a potential means to monitor the health of loaded skin and soft tissues informing timely interventions of PU prevention.

Investigating the influence of intermittent and continuous mechanical loading on skin through non-invasive sampling of IL-1α

Pressure ulcers (PUs) are a major burden to both patients, carers and the healthcare system. It is therefore important to identify patients at risk and detect pressure ulcers at an early stage of their development. The pro-inflammatory cytokine IL-1α is a promising indicator of tissue damage. The aim of this study was to compare the temporal skin response, by means of IL-1α expression, to different loading regimens and to investigate the presence of individual variability. The sacrum of eleven healthy volunteers was subjected to two different loading protocols. After a baseline measurement, the left and right side of the sacrum were subjected to continuous and intermittent loading regimen, respectively, at a pressure of 100 mmHg. Data was collected every 20 min, allowing for a total experimental time of 140 min. Sebum, collected at ambient conditions using Sebutape, was analyzed for the pro-inflammatory cytokine IL-1α. Most robust results were obtained using a baseline normalization approach on individual data. The IL-1α level significantly changed upon load application and removal (p<0.05) for both loading regimens. Highest IL-1α ratio increase, 3.7-fold, was observed for 1 h continuous loading. During the refractory periods for both loading regimen the IL-1α levels were still found to be up-regulated compared to baseline (p<0.05). The IL-1α level increased significantly for the two initial loading periods (p<0.05), but stabilized during the final loading period for both loading regimens. Large individual variability in IL-1α ratio was observed in the responses, with median values of 1.91 (range 1.49–3.08), and 2.52 (range 1.96–4.29), for intermittent and continuous loading, respectively, although the differences were not statistically significant. Cluster analysis revealed the presence of two distinct sub-populations, with either a low or high response to the applied loading regimen. The measurement after the first loading period proved to be representative for the subsequent measurements on each site. This study revealed that trends in normalized IL-1α provided an early indicator for tissue status following periods of mechanical loading and refractory unloaded conditions. Additionally, the observed individual variability in the response potentially identifies patients at risk of developing PUs.

Anisotropic mechanosensitive pathways in the diaphragm and their implications in muscular dystrophies.

The diaphragm is the "respiratory pump;" the muscle that generates pressure to allow ventilation. Diaphragm muscles play a vital function and thus are subjected to continuous mechanical loading. One of its peculiarities is the ability to generate distinct mechanical and biochemical responses depending on the direction through which the mechanical forces applied to it. Contractile forces originated from its contractile components are transmitted to other structural components of its muscle fibers and the surrounding connective tissue. The anisotropic mechanical properties of the diaphragm are translated into biochemical signals that are directionally mechanosensitive by mechanisms that appear to be unique to this muscle. Here, we reviewed the current state of knowledge on the biochemical pathways regulated by mechanical signals emphasizing their anisotropic behavior in the normal diaphragm and analyzed how they are affected in muscular dystrophies.

Fatigue study on the sensor performance of macro fiber composite (MFC): Theoretical and experimental approach

Due to its high flexibility and enhanced electro-mechanical coupling, macro fiber composite (MFC) is widely used in the area of sensing, vibration control and structural control. While in application, MFCs are subjected to continuous cyclic mechanical load which may lead to the deterioration of piezoelectric coupling coefficient, thereby affecting its sensing performance. In order to predict the life cycle of MFC (d31&d31 type) subjected to mechanical loading, an experimental setup has been devised and the tests are carried out for various loading conditions. For lowering the effort and cost involved in the experiments, a non-linear finite element model along with cumulative damage theory is introduced. The degradation in the piezoelectric coupling coefficient obtained using the current theoretical model are in good comparison with the experimental observations. The current non-linear FE model is also extended to predict the stiffnesses and strengths of the MFC as a function of fatigue cycles.

Effects of Biowastes Released by Mechanically Damaged Muscle Cells on the Propagation of Deep Tissue Injury: A Multiphysics Study.

Deep tissue injuries occur in muscle tissues around bony prominences under mechanical loading leading to severe pressure ulcers. Tissue compression can potentially compromise lymphatic transport and cause accumulation of metabolic biowastes, which may cause further cell damage under continuous mechanical loading. In this study, we hypothesized that biowastes released by mechanically damaged muscle cells could be toxic to the surrounding muscle cells and could compromise the capability of the surrounding muscle cells to withstand further mechanical loadings. In vitro, we applied prolonged low compressive stress (PLCS) and short-term high compressive stress to myoblasts to cause cell damage and collected the biowastes released by the damaged cells under the respective loading scenarios. In silico, we used COMSOL to simulate the compressive stress distribution and the diffusion of biowastes in a semi-3D buttock finite element model. In vitro results showed that biowastes collected from cells damaged under PLCS were more toxic and could compromise the capability of normal myoblasts to resist compressive damage. In silico results showed that higher biowastes diffusion coefficient, higher biowastes release rate, lower biowastes tolerance threshold and earlier timeline of releasing biowastes would cause faster propagation of tissue damage. This study highlighted the importance of biowastes in the development of deep tissue injury to clinical pressure ulcers under prolonged skeletal compression.

Mechanical Stretching of Mouse Calvarial Osteoblasts In Vitro Models Changes in MMP-2 and MMP-9 Expression at the Bone-Implant Interface.

Bone to mechanical loading elicits a biological response that has clinical significance for several areas in dental medicine, including orthodontic tooth movement, tempromandibular joint disease, and endosseous dental implant osseointegration. Human orthopedic studies of failed hip implant sites have identified increased mRNA expression of several collagen-degrading matrix metalloproteinases (MMPs), while in vitro experiments have shown increases in MMP secretion after exposure to inflammatory mediators. This investigation evaluates the effects of mechanical deformation on in vitro osteoblasts by assessing changes in MMP gene expression and enzyme activity. We seeded mouse neonatal calvarial osteoblasts onto flexible 6-well plates and subjected to continuous cyclic mechanical stretching. The expression and activity of mRNA for several MMPs (2, 3, 9, and 10) was assessed. When subjected to mechanical stress in culture, only mRNA specific for MMP-9 was significantly increased compared to nonstretched controls (P < .005). Measurement of MMP activity by gelatin zymography demonstrated that none of the MMPs showed increased activity with stretching; however, MMP-2 activity decreased. Our results suggest that in response to stretch, MMP-2 responds rapidly by inhibiting conversion of a MMP-2 to the active form, while a slower up-regulation of MMP-9 may play a role in the long-term remodeling of extracellular matrix in response to continuous mechanical loading. This study suggests that the regulation of metalloproteinases at both the mRNA and protein level are important in the response of bone to mechanical stress.

Inserted rest period resensitizes MC3T3-E1 cells to fluid shear stress in a time-dependent manner via F-actin-regulated mechanosensitive channel(s).

The underlying cellular mechanism of anabolic effect recovered by inserting rest is not fully understood. In this work, we studied the role of F-actin regulated mechanosensitive channel(s) re-activation in mechanosensitivity modulation in vitro. Results showed that steady fluid shear stress (sFSS) stimulation with 30-min rest period was more potential in increasing alkalinephosphatase (ALP) activity than 10 and 0-min rest periods, and insertion of 30 min, but not 0 or 10 min, recovered the [Ca(2+)]i transient and contribution of the mechanosensitive channel(s). During the rest period, F-actin experienced polymerization (0-10 min), followed by depolymerization (10-30 min); inhibition of F-actin polymerization/depolymerization significantly increased/decreased the [Ca(2+)]i transient, as well as the contribution of the mechanosensitive channel(s) in subsequent sFSS stimulation. Our results demonstrated that the long rest period between sFSS loadings recruited [Ca(2+)]i transient via F-actin depolymerization-induced reactivation of mechanosensitive channel(s), suggesting that F-actin-regulated cellular stiffness could account for the decreased anabolic response during continuous mechanical loading in bone cells.

Dynamic mechanical compression of devitalized articular cartilage does not activate latent TGF-β

A growing body of research has highlighted the role that mechanical forces play in the activation of latent TGF-β in biological tissues. In synovial joints, it has recently been demonstrated that the mechanical shearing of synovial fluid, induced during joint motion, rapidly activates a large fraction of its soluble latent TGF-β content. Based on this observation, the primary hypothesis of the current study is that the mechanical deformation of articular cartilage, induced by dynamic joint motion, can similarly activate the large stores of latent TGF-β bound to the tissue extracellular matrix (ECM).Here, devitalized deep zone articular cartilage cylindrical explants (n=84) were subjected to continuous dynamic mechanical loading (low strain: ±2% or high strain: ±7.5% at 0.5Hz) for up to 15h or maintained unloaded. TGF-β activation was measured in these samples over time while accounting for the active TGF-β that remains bound to the cartilage ECM. Results indicate that TGF-β1 is present in cartilage at high levels (68.5±20.6ng/mL) and resides predominantly in the latent form (>98% of total). Under dynamic loading, active TGF-β1 levels did not statistically increase from the initial value nor the corresponding unloaded control values for any test, indicating that physiologic dynamic compression of cartilage is unable to directly activate ECM-bound latent TGF-β via purely mechanical pathways and leading us to reject the hypothesis of this study.These results suggest that deep zone articular chondrocytes must alternatively obtain access to active TGF-β through chemical-mediated activation and further suggest that mechanical deformation is unlikely to directly activate the ECM-bound latent TGF-β of various other tissues, such as muscle, ligament, and tendon.

OS1105 微小溝内における腱細胞の配列培養と力学応答解析(生体の材料力学,OS-11 生体の材料力学)

Tendon is subjected to continuous mechanical loading, which imposes cyclic tensile strain and interstitial fluid shear stress to tenocytes. Although a number of studies have characterized mechanical responses of tenocytes to cyclic tensile strain, only few studies have been performed to examine tenocyte responses to fluid shear stress. The present study proposes a newly fabricated cell culture device using MEMS technologies, which enables to apply cyclic tensile strain or fluid shear stress, or both simultaneously, to tenocytes seeded onto microgrooves. It was confirmed that tenocytes exhibited a similar morphology as observed in vivo. Numerical analysis of flow patterns within the device demonstrated that a wide range of fluid shear stress, including a previously predicted physiological value, could be applied to cells. In summary, the present study developed a novel experimental model, which will reveal further details of tenocyte mechanotransduction events.

Effects of mechanical load on the degradation of poly( d, l-lactic acid) foam

Degradable behaviors of polymer for implantation in body should be evaluated before clinical application. The effect of continuous mechanical load on the degradation progress of poly( d, l-lactic acid) (PDLLA) foam gasket was investigated in detail by specially designed load-providing devices. While PDLLA degraded in the PBS solution (pH, 7.4) at 37 °C for 3 months, the changes of surface morphology, molecular weight, elastic modulus, tensile strength and mass loss were recorded. The results revealed that the degradation rates of PDLLA under continuous loads were obviously quicker than those without load. Moreover, the influence of tensile plus compressive load was larger than that of tensile load. It was indicated that in vivo degradation of PDLLA would not only be influenced by the local solution, but also by the surrounding load. When regulating the degradation rate of bioabsorbable polymer, one should consider the indispensable effect of load where implanted.

Influence of perfusion and cyclic compression on proliferation and differentiation of bone marrow stromal cells in 3-dimensional culture

Until now, there has been no in vitro model that duplicates the environment of bone marrow. The purpose of this study was to analyze proliferation and differentiation of human bone marrow stromal cells (hBMSC) under the influence of continuous perfusion and cyclic mechanical loading. hBMSC of seven individuals were harvested, grown in vitro, and combined. 10 6 hBMSC were seeded on a bovine spongiosa disc and incubated in a bioreactor system. Cell culture was continued using three different conditions: Continuous perfusion (group A), 10% cyclic compression at 0.5 Hz (group B) and static controls (group C). After 24 h, 1, 2, and 3 weeks, we determined cell proliferation (MTS-assay) and osteogenic differentiation (osteocalcin ELISA, Runx2 mRNA). Tenascin-C mRNA was quantified to exclude fibroblastic differentiation. In groups A and B, proliferation was enhanced after 2 weeks (48.6±19.6×10 3 (A) and 44.6±14.3×10 3 cells (B)) and after 3 weeks (46.6±15.1×10 3 (A) and 44.8±10.2×10 3 cells (B)) compared with controls (26.3±10.8×10 3 (2 weeks) and 17.1±6.5×10 3 cells (3 weeks), p<0.03). Runx2 mRNA was upregulated in both stimulated groups after 1, 2, and 3 weeks compared to control (group A, 1 week: 5.2±0.7-fold; p<0.01, 2 weeks: 4.4±1.9-fold; p<0.01, 3 weeks: 3.8±1.7-fold; p=0.013; group B, 1 week: 3.6±1.1-fold, p<0.01, 2 weeks: 4.2±2.2-fold, p<0.01; 3 weeks: 5.3±2.7-fold, p<0.01). hBMSC stimulated by cyclic compression expressed the highest amount of osteocalcin at all time points (1 week: 294.5±88.4 mg/g protein, 2 weeks: 294.4±73.3 mg/g protein, 3 weeks: 293.1±83.6 mg/g protein, p⩽0.03). The main stimulus for cell proliferation in a 3-dimensional culture of hBMSC is continuous perfusion whereas mechanical stimulation fosters osteogenic commitment of hBMSC. This study thereby contributes to the understanding of physical stimuli that influence hBMSC in a 3-dimensional cell culture system.

Theoretical model of acoustic emission under mechanical loading of rocks in the maximum compaction region

A theoretical model of changes in acoustic emission activity in a geomaterial under continuous or stepwise mechanical loading is justified. Based on this model, the experimentally found laws of emission in the region of the maximum compaction of rock samples with different rates of mechanical loading of these samples are analyzed.

The transformation of spinal curvature into spinal deformity: pathological processes and implications for treatment

BackgroundThis review summarizes what is known about the pathological processes (e.g. structural and functional changes), by which spinal curvatures develop and evolve into spinal deformities.MethodsComprehensive review of articles (English language only) published on 'scoliosis,' whose content yielded data on the pathological changes associated with spinal curvatures. Medline, Science Citation Index and other searches yielded > 10,000 titles each of which was surveyed for content related to 'pathology' and related terms such as 'etiology,' 'inheritance,' 'pathomechanism,' 'signs and symptoms.' Additional resources included all books published on 'scoliosis' and available through the Arizona Health Sciences Library, Interlibrary Loan, or through direct contact with the authors or publishers.ResultsA lateral curvature of the spine–'scoliosis'–can develop in association with postural imbalance due to genetic defects and injury as well as pain and scarring from trauma or surgery. Irrespective of the factor that triggers its appearance, a sustained postural imbalance can result, over time, in establishment of a state of continuous asymmetric loading relative to the spinal axis. Recent studies support the longstanding hypothesis that spinal deformity results directly from such postural imbalance, irrespective of the primary trigger, because the dynamics of growth within vertebrae are altered by continuous asymmetric mechanical loading. These data suggest that, as long as growth potential remains, evolution of a spinal curvature into a spinal deformity can be prevented by reversing the state of continuous asymmetric loading.ConclusionSpinal curvatures can routinely be diagnosed in early stages, before pathological deformity of the vertebral elements is induced in response to asymmetric loading. Current clinical approaches involve 'watching and waiting' while mild reversible spinal curvatures develop into spinal deformities with potential to cause symptoms throughout life. Research to define patient-specific mechanics of spinal loading may allow quantification of a critical threshold at which curvature establishment and progression become inevitable, and thereby yield strategies to prevent development of spinal deformity.Even within the normal spine there is considerable flexibility with the possibility of producing many types of curves that can be altered during the course of normal movements. To create these curves during normal movement simply requires an imbalance of forces along the spine and, extending this concept a little further, a scoliotic curve is produced simply by a small but sustained imbalance of forces along the spine. In fact I would argue that no matter what you believe to be the cause of AIS, ultimately the problem can be reduced to the production of an imbalance of forces along the spine [1].