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BACKGROUND Skin sensitivity (SS) is a commonly occurring response to a range of stimuli, including environmental conditions (e.g., sun exposure), chemical irritants (e.g., soaps and cosmetics), and mechanical forces (e.g., while shaving). From both industry and academia, many efforts have been taken to quantify the characteristics of SS in a standardised manner, but the study is hindered by the lack of an objective definition. METHODS A review of the scientific literature regarding different parameters attributed to the loss of skin integrity and linked with exhibition of SS was conducted. Articles included were screened for mechanical stimulation of the skin, with objective quantification of tissue responses using biophysical or imaging techniques. Additionally, studies where cohorts of SS and non-SS individuals were reported have been critiqued. RESULTS The findings identified that the structure and function of the stratum corneum and its effective barrier properties are closely associated with SS. Thus, an array of skin tissue responses has been selected for characterization of SS due to mechanical stimuli, including: transepidermal water loss, hydration, redness, temperature, and sebum index. Additionally, certain imaging tools allow quantification of the superficial skin layers, providing structural characteristics underlying SS. CONCLUSION This review proposes a multimodal approach for identification of SS, providing a means to characterise skin tissue responses objectively. Optical coherence tomography (OCT) has been suggested as a suitable tool for dermatological research with clinical applications. Such an approach would enhance the knowledge underlying the multifactorial nature of SS and aid the development of personalised solutions in medical and consumer devices.

Background: Penile compression devices (PCD) or clamps are applied to compress the urethra and prevent urinary incontinence (UI). PCDs are more secure and less likely to leak than pads, allowing men the opportunity to participate in short-term, vigorous activities. However, they are uncomfortable, can cause pressure ulcers (PU) and affect penile blood flow. No objective assessment of tissue health has been undertaken to assess and compare different PCD designs and to provide guidance on safe use. Objective: This study was designed to evaluate existing PCDs in terms of their physiological response and potential for pressure-induced injury. Design, setting and participants: Six men with post-prostatectomy UI tested four selected PCDs at effective pressures, in a random order, in a controlled laboratory setting. Outcome measurements and statistical analysis: Using objective methods for assessing skin injury, PCDs were measured in situ for their effects on circulatory impedance, interface pressures and inflammatory response. Results and limitations: There was evidence for PCD-induced circulatory impedance in most test conditions. Interface pressures varied considerably between both PCDs and participants, with a mean value of 137.4±69.7 mmHg. In some cases, penile skin was noted to be sensitive to loading with elevated concentration of the cytokine IL-1α after 10 mins wear, indicating an inflammatory response. IL-1α levels were restored to baseline 40 mins following PCD removal. Conclusion: Skin health measures indicated tissue and blood flow compromise during the 50 mins of testing using all PCDs. Although there was an elevation in pro-inflammatory cytokines, PCDs did not cause sustained irritation and skin health measures recovered 40 mins after PCD removal. This research indicates that application of a clamp for one hour with an equal clamp free time before reapplication is likely to be safe. Longer periods are often recommended by manufacturers but have yet to be tested.

Since the outbreak of COVID‐19 pandemic, clinicians have had to use personal protective equipment (PPE) for prolonged periods. This has been associated with detrimental effects, especially in relation to the skin health. The present study describes a comprehensive survey of healthcare workers (HCWs) to describe their experiences using PPE in managing COVID‐19 patients, with a particular focus on adverse skin reactions. A 24‐hour prevalence study and multi‐centre prospective survey were designed to capture the impact of PPE on skin health of hospital staff. Questionnaires incorporated demographics of participants, PPE type, usage time, and removal frequency. Participants reported the nature and location of any corresponding adverse skin reactions. The prevalence study included all staff in intensive care from a single centre, while the prospective study used a convenience sample of staff from three acute care providers in the United Kingdom. A total of 108 staff were recruited into the prevalence study, while 307 HCWs from a variety of professional backgrounds and demographics participated in the prospective study. Various skin adverse reactions were reported for the prevalence study, with the bridge of the nose (69%) and ears (30%) being the most affected. Of the six adverse skin reactions recorded for the prospective study, the most common were redness blanching (33%), itchiness (22%), and pressure damage (12%). These occurred predominantly at the bridge of the nose and the ears. There were significant associations (P

Background: pressure mapping technology has been adapted to monitor over prolonged periods to evaluate pressure ulcer risk in individuals during extended lying postures. However, temporal pressure distribution signals are not currently used to identify posture or mobility. The present study was designed to examine the potential of an automated approach for the detection of a range of staticlying postures and corresponding transitions between postures.Methods: healthy subjects (n=19) adopted a range of sagittal and lateral lying postures. Parameters reflecting both the interactions at the support surface and body movements were continuously monitored. Subsequently, the derivative of each signal was examined to identify transitions between postures. Three machine learning algorithms, namely Naïve-Bayes, k-Nearest Neighbors and Support Vector Machine classifiers, were assessed to predict a range of static postures, established with a training model (n=9) and validated with new input from test data (n=10). Findings: results showed that the derivative signals provided a means to detect transitions between postures, with actimetry providing the most distinct signal perturbations. The accuracy in predicting the range of postures from new test data ranged between 82%-100%, 70%-98% and 69%-100% for Naïve-Bayes, k-Nearest Neighbors and Support Vector Machine classifiers, respectively.Interpretation: the present study demonstrated that detection of both static postures and their corresponding transitions was achieved by combining machine learning algorithms with robust parameters from two monitoring systems. This approach has the potential to provide reliable indicators of posture and mobility, to support personalized pressure ulcer prevention strategies.

Background High strain in soft tissues that overly bony prominences are considered a risk factor for pressure ulcers (PUs) following spinal cord impairment (SCI) and have been computed using Finite Element methods (FEM). The aim of this study was to translate a MRI protocol into ultrasound (US) and determine between-operator reliability of expert sonographers measuring diameter of the inferior curvature of the ischial tuberosity (IT) and the thickness of the overlying soft tissue layers on able-bodied (AB) and SCI using real-time ultrasound. Material and methods Part 1: Fourteen AB participants with a mean age of 36.7 ± 12.09 years with 7 males and 7 females had their 3 soft tissue layers in loaded and unloaded sitting measured independently by 2 sonographers: tendon/muscle, skin/fat and total soft tissue and the diameter of the IT in its short and long axis. Part 2: Nineteen participants with SCI were screened, three were excluded due to abnormal skin signs, and eight participants (42%) were excluded for abnormal US signs with normal skin. Eight SCI participants with a mean age of 31.6 ± 13.6 years and all male with 4 paraplegics and 4 tetraplegics were measured by the same sonographers for skin, fat, tendon, muscle and total. Skin/fat and tendon/muscle were computed. Results AB between-operator reliability was good (ICC = 0.81–0.90) for 3 soft tissues layers in unloaded and loaded sitting and poor for both IT short and long axis (ICC = −0.028 and −0.01). SCI between-operator reliability was good in unloaded and loaded for total, muscle, fat, skin/fat, tendon/muscle (ICC = 0.75–0.97) and poor for tendon (ICC = 0.26 unloaded and ICC = −0.71 loaded ) and skin (ICC = 0.37 unloaded and ICC = 0.10). Conclusion A MRI protocol was successfully adapted for a reliable 3 soft tissue layer model and could be used in a 2-D FEM model designed to estimate soft tissue strain as a novel risk factor for the development of a PU.

BackgroundSpinal immobilisation using a rigid long spineboard is a well-established procedure in trauma care. During immobilisation, the body is exposed to high tissue-interface pressures. This may lead to a localised inflammatory response of the skin, which may be used to monitor the body's response to different types of immobilisation device.AimIn this study we compared the standard rigid spineboard with a new soft-layered spineboard regarding tissue-interface pressures, skin redness as an indicator of reactive hyperaemia and cutaneous IL1α and lactate release.MethodsTwelve healthy male participants were asked to lie supine on both a rigid and a soft-layered spineboard, loading the sacrum for one hour, followed by one hour in unloaded position. Tissue-interface pressures on the buttocks during loading were measured continuously using a pressure mapping mat. Cutaneous IL1α and lactate concentrations were assessed using Sebutapes, during 20-minute periods. After each 20-minute period, a photo of the buttocks was taken, which was later assessed for redness by two observers.ResultsSignificant differences in tissue-interface pressure and reactive hyperaemia were found between the two types of spineboard. Release of IL1α and lactate were found to increase with prolonged exposure to pressure, and to decrease in the unloaded prone position. A significant relationship was found between tissue-interface pressure and reactive hyperaemia, but not with IL1α nor lactate release. Time course of IL1α and lactate release was similar for both types of spineboard.ConclusionsIL1α and lactate both have a strong relationship with pressure exposure time, but not with pressure magnitude. Furthermore, IL1α was measured even in the absence of visible redness of the skin. The study offers the potention of biomarkers, reflecting inflammation and/or tissue metabolism, for use in assessing the effects of prolonged spineboard support.

Articular cartilage with its inherently poor capacity for self-regeneration represents a primary target for tissue engineering strategies, with approaches focusing on the in vitro generation of neo-cartilage using chondrocyte-seeded 3D scaffolds subjected to mechanical conditioning. Although uniaxial compression regimens have significantly up-regulated proteoglycan synthesis, their effects on the synthesis of collagen have been modest. Articular cartilage is subjected to shear forces during joint motion. Accordingly, this study utilized an apparatus to apply biaxial loading to chondrocytes seeded within agarose constructs with endplates. The chondrocytes yielded a monotonic increase in proteoglycan synthesis both in free swelling culture up to day 8 and when the constructs were subjected to dynamic compression alone (15% amplitude at a frequency of 1 Hz for 48 h). However, when dynamic shear (10% amplitude at 1 Hz) was superimposed on dynamic compression, total collagen synthesis was also up-regulated, within 3 days of culture, without compromising proteoglycan synthesis. Histological analysis revealed marked collagen deposition around individual chondrocytes. A significant proportion (50%) of collagen was released into the culture medium, suggesting that it had only been partially synthesized in its mature state. The overall biosynthetic activity was enhanced more when the biaxial stimulation was applied in a continuous mode as opposed to intermittent loading. Results of the present study strongly suggest that proteoglycan and collagen synthesis may be triggered by uncoupled mechanosensitive cellular responses. The proposed in vitro model and the prescribed conditioning protocols demonstrated that a short pre-culture period is preferable to long free swelling culture condition as it enables a significantly higher up-regulation of collagen. Biotechnol. Bioeng. 2017;114: 1614-1625. © 2017 Wiley Periodicals, Inc.

STUDY DESIGN A biomechanical study using bovine thoracolumbar spines. OBJECTIVE To study investigated whether thread design parameters aimed at altering the state of stress at the screw-bone interface increase the screw's holding power. SUMMARY AND BACKGROUND DATA Internal spinal fixators utilizing transpedicular screw fixation are used to achieve early stabilization of the injured spine in a range of clinical conditions. Despite advances in the design of internal spinal fixation systems, implant loosening, and catastrophic failures at the screw-bone interface remains a serious complication in adult spine surgery. Although the performance of the screws in the vertebral bone critically depends on ability of screw thread design to provide and maintain adequate bone purchase, the effect of individual thread design parameters on screw performance and the failure process of the screw-bone interface, remains unclear. METHODS On the basis of the AO Schanz thread, this parametric study used 96 lumbar bovine vertebrae instrumented with 19 screw designs to investigate the effects of pitch, ratio of major to minor diameter, screw insertion depth, and major diameter, on screw performance under pure tensile loading. The effect of vertebral morphometry on screw performance and the extent of damage within the failed screw-bone interface were evaluated. RESULTS The increase in screw insertion depth, screw pitch, and the ratio of major to minor diameter, significantly affected screw performance under tensile loads. Complex interactions existed between the major diameter and each of the design variables. Vertebral morphometry had little effect on screw performance while the damage within the failed bone-screw interface confined to the immediate region of the screw threads. CONCLUSIONS Design variables, able to reduce shear stresses or modify the complex stress profile at the bone-screw interface, are more effective in preventing early failure of the interface.

Pressure mapping systems have been traditionally used to assess load distributions in individuals at risk of pressure ulcers. Recently, the technology has been adapted to monitor pressures over prolonged periods. The present study aims to investigate the predictive ability of selected biomechanical parameters estimated from pressure distributions for detecting postural changes in lying. Healthy participants (n = 11) were recruited and positioned in different lying postures, by utilizing the head of bed (HOB) angle and an automated tilting system to achieve evoked movements in the sagittal and transverse planes, respectively. Measurements included continuous monitoring of interface pressures and accelerations from the trunk and waist. Selected interface pressure parameters included; centre of pressure, contact area and pressure gradient. A threshold range for all parameters was established and Receiver Operating Characteristic (ROC) curves presented to determine the sensitivity and specificity for detecting postural changes. Temporal trends in the data revealed significant variance in the signal perturbations during each evoked postural change. Indeed, sensitivity and specificity were influenced by the specific threshold values and the relative position of the individual. As an example, sensitivity of some parameters exhibited a compromised trend at higher HOB angles, with low corresponding area under the ROC curve. By contrast, contact area provided the highest values, with 7/12 signals achieve AUC >0.5. This corresponded with actimetry signals, which provided high discrimination between postures. Parameters estimated from a commercial pressure monitoring can have the potential to detect postural changes. Further research is required to convert the data into meaningful clinical information, to inform patient repositioning strategies.

Aim: prolonged mechanical loading on soft tissues adjacent to bony prominences can lead to pressure ulcers. The presence of moisture at the skin interface will lower the tolerance to load. Absorbent pads manage moisture in individuals with incontinence, although their role in maintaining skin health is unknown. The present study investigated the effects of moist incontinence pads on skin physiology after periods of mechanical loading.Material and methods: twelve healthy participants were recruited to evaluate a single incontinence pad design under three moisture conditions: 0% (dry), 50% and 100% fluid capacity. For each pad condition, pressure (9 kPa) or pressure in combination with shear (3 N) was applied to the sacrum, followed by a period of off-loading. Measures included trans-epidermal water loss (TEWL) and inflammatory biomarkers sampled at the skin interface.Results: results revealed no change in TEWL in the loaded dry pad condition. By contrast, when the pads contained moisture, significant increases in TEWL were observed. These increases were reversed during off-loading. Inflammatory biomarkers, specifically IL-1α/total protein ratio, were up-regulated during dry pad loading, which recovered during off-loading. Loaded moist pads caused a significant increase in biomarkers, which remained elevated throughout the test period.Conclusion: the study revealed a marked compromise to stratum corneum integrity when the skin was exposed to moist incontinence pads in combination with mechanical loads. These physiological changes were largely reversed during off-loading. Incontinence pads provided some protection in the dry state, although more research is required to determine optimal clinical guidance for their use.

BackgroundMechanical conditioning has been widely used to attempt to enhance chondrocyte metabolism for the evolution of functionally competent cartilage. However, although upregulation of proteoglycans have been reported through the application of uniaxial compression, minimal collagen has been produced. The study is designed to examine whether alternative loading regimens, equivalent to physiological conditions, involving shear in addition to compression can enhance collagen production.MethodsFinite element models were developed to determine how the local chondrocyte environments within agarose constructs were influenced by a range of static and dynamic loading regimens. 3-D poro-viscoelastic models were validated against experimental data. In particular, these models were used to characterise chondrocyte deformation in compression with and without shear superimposed, with special reference to the formation of pericellular matrix around the cells.FindingsThe models of the hydrogel constructs under stress relaxation and dynamic cyclic compression conditions were highly correlated with the experimental data. The cell deformation (y/z) in the constructs was greatest in the centre of the constructs, increasing with magnitude of compression up to 25%. The superposition of shear however did not produce significant additional changes in deformation, with the presence of PCM reducing the chondrocyte deformation.InterpretationThe use of FE models can prove important in the definition of appropriate, optimised mechanical conditioning regimens for the synthesis and organisation of mature extra cellular matrix by chondrocyte-seeded constructs. They will also provide insight into the mechanisms relating cell deformation to mechanotransduction pathways, thereby progressing the development of functionally competent tissue engineered cartilage.

Objective and design: Oxygen tension and biomechanical signals are factors that regulate inflammatory mechanisms in chondrocytes. We examined whether low oxygen tension influenced the cells response to TNF? and dynamic compression.Materials and methods: Chondrocyte/agarose constructs were treated with varying concentrations of TNF? (0.1–100 ng/ml) and cultured at 5 and 21 % oxygen tension for 48 h. In separate experiments, constructs were subjected to dynamic compression (15 %) and treated with TNF? (10 ng/ml) and/or L-NIO (1 mM) at 5 and 21 % oxygen tension using an ex vivo bioreactor for 48 h. Markers for catabolic activity (NO, PGE2) and tissue remodelling (GAG, MMPs) were quantified by biochemical assay. ADAMTS-5 and MMP-13 expression were examined by real-time qPCR. 2-way ANOVA and a post hoc Bonferroni-corrected t test were used to analyse data.Results: TNF? dose-dependently increased NO, PGE2 and MMP activity (all p < 0.001) and induced MMP-13 (p < 0.05) and ADAMTS-5 gene expression (pp < 0.01) with values greater at 5 % oxygen tension than 21 %. The induction of catabolic mediators by TNF? was reduced by dynamic compression and/or L-NIO (all p < 0.001), with a greater inhibition observed at 5% than 21 %. The stimulation of GAG synthesis by dynamic compression was greater at 21 % than 5 % oxygen tension and this response was reduced with TNF? or reversed with L-NIO.Conclusions: The present findings revealed that TNF? increased production of NO, PGE2 and MMP activity at 5 % oxygen tension. The effects induced by TNF? were reduced by dynamic compression and/or the NOS inhibitor, linking both types of stimuli to reparative activities. Future therapeutics should develop oxygen-sensitive antagonists which are directed to interfering with the TNF?-induced pathways.

Background: Ultrasonography may have potential as an effective diagnostic tool for deep tissue injury (DTI) in tissues overlying bony prominences that are vulnerable when under sustained loading in sitting. Methods: Three cases of DTI in the fat and muscle layers overlying the ischial tuberosity of the pelvis in 3 persons with spinal cord injury (SCI) with different medical histories and abnormal tissue signs are described. Conclusion: There is a need for prospective studies using a reliable standardized ultrasonography protocol to diagnose DTI and to follow its natural history to determine its association with the development of pressure injuries.

Background The ankle joint is a common site of musculoskeletal pathology. Measurement of its functional range of motion is a primary indicator for rehabilitation outcomes in therapy settings. The present study was designed to assess reliability and validity of a new standardised method using a D-Flex device to assess ankle range of motion. Methods A cohort of 20 healthy volunteers were recruited to measure the weight-bearing ankle range of motion using three assessment tools, namely, a goniometer, inclinometer and the D-Flex measurement devices. Repeated measures were performed both between and within observers for each device over a 48 h period. Performance evaluation of each device and their reliability was assessed using intra-class correlation coefficients and Bland and Altman plots. Results Although significant correlations (p

Triceps surae eccentric exercise is more effective than concentric exercise for treating Achilles tendinopathy, however the mechanisms underpinning these effects are unclear. This study compared the biomechanical characteristics of eccentric and concentric exercises to identify differences in the tendon load response. Eleven healthy volunteers performed eccentric and concentric exercises on a force plate, with ultrasonography, motion tracking, and EMG applied to measure Achilles tendon force, lower limb movement, and leg muscle activation. Tendon length was ultrasonographically tracked and quantified using a novel algorithm. The Fourier transform of the ground reaction force was also calculated to investigate for tremor, or perturbations. Tendon stiffness and extension did not vary between exercise types (P = .43). However, tendon perturbations were significantly higher during eccentric than concentric exercises (25%–40% higher, P = .02). Furthermore, perturbations during eccentric exercises were found to be negatively correlated with the tendon stiffness (R2 = .59). The particular efficacy of eccentric exercise does not appear to result from variation in tendon stiffness or extension within a given session. However, varied perturbation magnitude may have a role in mediating the observed clinical effects. This property is subject-specific, with the source and clinical timecourse of such perturbations requiring further research.

Lymphedema is a chronic peripheral swelling caused by a dysfunction of the lymphatic system, leading to discomfort and loss of upper limb movement. Therapies to treat or manage this swelling have limited evidence, partly because of a paucity in objective lymphatic measures. This study explored the role of near-infrared (NIR) imaging in evaluating interventions.Nine healthy volunteers underwent NIR fluoroscopy using a microdose (50 μL, 0.05% w/v) of indocyanine green to quantify lymphatic behavior before and after a 15-minute period of manual lymph drainage followed by compression garment (CG) therapy for a 10-minute period. Images were taken at the forearm and elbow after each intervention. Lymphatic function was defined by the number, size, displacement, and speed of lymph packets. The lymph parameters were analyzed to assess the effects of the interventions compared with basal values.Baseline (BL) parameters of lymph function revealed high variability in the number, size, and speed of packets between individuals. Despite this variance, both interventions showed statistically significant improvement (p 0.05) in displacement and speed at the forearm compared with BL. The velocity of transient lymph packets increased from a median of 6.7 mm/s at BL to 13.3 mm/s after manual lymphatic drainage (MLD) and 10.5 mm/s after CG.Lymphatic activity increased significantly after MLD, with relative increases being maintained after a short time period of CG application. NIR fluoroscopy has the potential to both monitor lymph pathology and provide robust parameters in the assessment of interventions.

Physiological loading is essential for the maintenance of articular cartilage by regulating tissue remodelling, in the form of both catabolic and anabolic processes. To promote the development of tissue engineered cartilage which closely matches the long term functionality of native tissue, bioreactors have been developed to provide a combination of loading modalities, which reflect the nature of normal physiological loads. This study describes the design and validation of an in vitro mechanical system for the controlled application of bi-axial loading regimes to chondrocyte-seeded agarose constructs. The computer-controlled system incorporates a robust gripping system, which ensures the delivery of precise values of cyclic compressive and shear strain to 3D cell-seeded constructs. Sample prototypes were designed, optimised using finite element analysis and validated performing compressive and shear fatigue mechanical tests. The horizontal and vertical displacements within the bioreactor are precisely controlled by a dedicated programme that can be easily implemented. The synchronisation of the orthogonal displacements was shown to be accurate and reproducible. Constructs were successfully loaded with a combined compressive and shear loading regimen at 1 Hz for up to 48 h with no appreciable loss of cell viability or mechanical integrity. These features along with the demonstrated high consistency make the system ideally suitable for a systematic investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.

AIMS Prostate cancer is the most frequently diagnosed male cancer and urinary incontinence represents a major consequence following surgery. Penile compression clamps (PCCs) which externally occlude the urethra may be used to manage the incontinence. Despite potential complication of PCCs, such as deformation-inflicted tissue damage, to date, there are no reported biomechanical criteria for design of PCCs, in terms of quantitative parameters for evaluating the safety-versus-efficacy of existing or future designs. METHODS We developed a set of computational three-dimensional models of the penis, to which compression was applied using five generic PCC designs. The internal mechanical states of the soft tissues of the penis were then analysed using finite element simulations. RESULTS Stresses in skin, fat, and tunica albuginea regularly exceeded 10 kPa (75 mmHg). Cuff-type and knurl-type PCCs pose the highest potential risks to tissue health with elevated tissue stresses around the entire penile perimeter (cuff) or urethral stress concentrations (knurl). The soft and contoured PCCs produced the lowest values of these mechanical parameters. CONCLUSIONS The present study identified design characteristics, including envelopment, adaptability, and durability which provide the safest mechanical conditions in the penis and thus minimize the risk of tissue damage while still managing incontinence. Such data should help to design a safer clamp.

Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. Tissue deformation may play an important role in the aetiology, which can be investigated using an experimental–numerical approach. Recently, an animal-specific finite element model has been developed to simulate experiments in which muscle tissue was compressed with an indenter. In this study, the material behaviour and boundary conditions were adapted to improve the agreement between model and experiment and to investigate the influence of these adaptations on the predicted strain distribution. The use of a highly nonlinear material law and including friction between the indenter and the muscle both improved the quality of the model and considerably influenced the estimated strain distribution. With the improved model, the required sample size to detect significant differences between loading conditions can be diminished, which is clearly relevant in experiments involving animals.

It is proposed that direct mechanical loading can impair dermal lymphatic function, contributing to the causal pathway of pressure ulcers. The present study aims to investigate the effects of loading on human dermal lymphatic vessels. Ten participants were recruited with ages ranging from 24-61 years. Participants had intradermal indocyanine green injections administrated between left finger digits. Fluorescence was imaged for 5 minute sequences with an Infra-Red camera prior to lymph vessel loading, immediately after axial loading (60mmHg) and following a recovery period. Image processing was employed to defined transient lymph packets and compare lymph function between each test phase. The results revealed that between 1-8 transient events (median =4) occurred at baseline, with a median velocity of 8.1mm/sec (range 4.1-20.1mm/sec). Immediately post-loading, there was a significant (p The present study revealed that some individuals present with impaired dermal lymphatic function immediately after uniaxial mechanical loading. More research is needed to investigate the effects of pressure and shear on lymphatic vessel patency.

Contains fulltext : 172112.pdf (Publisher’s version ) (Open Access) AIM: The study aimed to characterize demographic and clinical practice factors associated with community (CAPU) and hospital acquired pressure ulcers (HAPU). DESIGN: A comparative retrospective evaluation of pressure ulcer data, collected from a district general hospital. METHODS: Demographic and pressure ulcer related data were collected from patients at risk of developing a pressure ulcer, collated by a single observer using a standardized tool. Comparisons were made within and between patient groups (no PU, CAPU and HAPU). RESULTS: CAPU and HAPU patient groups were significantly (P < 0.001) older, had extended lengths of hospital stay and were less likely to be provided quickly with a pressure relieving support surface than those with no PU. HAPU patients had a longer length of stay and a higher proportion of heel PUs compared to CAPU.

This study adopts a combined computational and experimental approach to determine the mechanical, structural, and metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series of linear elastic and hyperelastic finite-element models demonstrated that chondrocytes cultured for 24 h in gels for which the relaxation modulus is

Biomechanical signals play an important role in normal disc metabolism and pathology. For instance, nucleus pulposus (NP) cells will regulate metabolic activities and maintain a balance between the anabolic and catabolic cascades. The former involves factors such as transforming growth factor-β (TGFβ) and mechanical stimuli, both of which are known to regulate matrix production through autocrine and paracrine mechanisms. The present study examined the combined effect of TGFβ and mechanical loading on anabolic activities in NP cells cultured in agarose constructs. Stimulation with TGFβ and dynamic compression reduced nitrite release and increased matrix synthesis and gene expression of aggrecan and collagen type II. The findings from this work has the potential for developing regenerative treatment strategies which could either slow down or stop the degenerative process and/or promote healing mechanisms in the intervertebral disc.

Delivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the outer layer of the skin in therapeutic amounts, but also macromolecules. To provide insight into the administration of these molecules into the skin, the aim of this study was to assess the transport of macromolecules within and between its various layers. The diffusion coefficients in the epidermis and several locations in the papillary and reticular dermis were determined for fluorescein dextran of 40 and 500 kDa using a combination of fluorescent recovery after photobleaching experiments and finite element analysis. The diffusion coefficient was significantly higher for 40 kDa than 500 kDa dextran, with median values of 23 and 9 µm(2)/s in the dermis, respectively. The values only marginally varied within and between papillary and reticular dermis. For the 40 kDa dextran, the diffusion coefficient in the epidermis was twice as low as in the dermis layers. The adopted method may be used for other macromolecules, which are of interest for dermal and transdermal drug delivery. The knowledge about diffusion in the skin is useful to optimize (trans)dermal drug delivery systems to target specific layers or cells in the human skin.

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.

Gap junction communication is an essential component in the mechanosensitive response of tenocytes. However, little is known about direct mechanoregulation of gap junction turnover and permeability. The present study tests the hypothesis that mechanical loading alters gap junction communication between tenocyte within tendon fascicles. Viable tenocytes within rat tail tendon fasicles were labelled with calcein-AM and subjected to a fluorescent loss induced by photobleaching (FLIP) protocol. A designated target cell within a row of tenocytes was continuously photobleached at 100% laser power whilst recording the fluorescent intensity of neighbouring cells. A mathematical compartment model was developed to estimate the intercellular communication between tenocytes based upon the experimental FLIP data. This produced a permeability parameter, k, which quantifies the degree of functioning gap functions between cells as confirmed by the complete inhibition of FLIP by the inhibitor 18α-glycyrrhentic acid. The application of 1N static tensile load for 10 min had no effect on gap junction communication. However, when loading was increased to 1 h, there was a statistically significant reduction in gap junction permeability. This coincided with suppression of connexin 43 protein expression in loaded samples as determined by confocal immunofluorescence. However, there was an upregulation of connexin 43 mRNA. These findings demonstrate that tenocytes remodel their gap junctions in response to alterations in mechanical loading with a complex mechanosensitive mechanism of breakdown and remodelling. This is therefore the first study to show that tenocyte gap junctions are not only important in transmitting mechanically activated signals but that mechanical loading directly regulates gap junction permeability.

Pressure ulcers are localized areas of soft tissue breakdown due to mechanical loading. Susceptible individuals are subjected to pressure relief strategies to prevent long loading periods. Therefore, ischemia-reperfusion injury may play an important role in the etiology of pressure ulcers. To investigate the inter-relation between postischemic perfusion and changes in skeletal muscle integrity, the hindlimbs of Brown Norway rats were subjected to 4-h ischemia followed by 2-h reperfusion. Dynamic contrast-enhanced MRI was used to examine perfusion, and changes in skeletal muscle integrity were monitored with T2-weighted MRI. The dynamic contrast-enhanced MRI data showed a heterogeneous postischemic profile in the hindlimb, consisting of areas with increased contrast enhancement (14-76% of the hindlimb) and regions with no-reflow (5-77%). For T2, a gradual increase in the complete leg was observed during the 4-h ischemic period (from 34 to 41 msec). During the reperfusion phase, a heterogeneous distribution of T2 was observed. Areas with increased contrast enhancement were associated with a decrease in T2 (to 38 msec) toward preischemic levels, whereas no-reflow areas exhibited a further increase in T2 (to 42 msec). These results show that reperfusion after prolonged ischemia may not be complete, thereby continuing the ischemic condition and aggravating tissue damage.

Extracellular matrix (ECM) in chondrocytes-seeded agarose aggregates to form islands of matrix. These islands need to coalesce to develop functional cartilage. Hence, macroscopic properties are determined by transport and aggregation of macromolecules at the microscale, which varies temporally and spatially. This study evaluates the importance of the mutual interaction between matrix components and matrix development. Fluorescence recovery after photobleaching measurements demonstrates that diffusivity depends on the presence and density of ECM. A reaction-diffusion model describing synthesis, transport and immobilisation of ECM predicts steep gradients in ECM around chondrocytes, resembling histology. Steric hindrance of diffusion by ECM is essential for the formation of these gradients. Finally, microscopic ECM concentration is linked with macroscopic mechanical properties. Construct softening is predicted when temporal and spatial variations in diffusivity are considered. In conclusion, non-constant diffusion renders significant effects on both the microscopic ECM development and the macroscopic mechanical properties of developing tissue-engineered cartilage.

Objective: To compare in vivo effects of eccentric and concentric calf muscle training on Achilles tendon stiffness, in subjects without tendinopathy.Methods: Thirty-eight recreational athletes completed 6 weeks eccentric (6 males, 13 females, 21.6 ± 2.2 years) or concentric training (8 males, 11 females, 21.1 ± 2.0 years). Achilles tendon stiffness, tendon modulus and single-leg jump height were measured before and after intervention. Exercise adherence was recorded using a diary.Results: All data are reported as mean ± SD. Groups were matched for height and weight but the eccentric training group were more active at baseline ( P Conclusions: Six weeks of eccentric training can alter Achilles tendon stiffness while a matched concentric programme shows no similar effects. Studies in patients with Achilles tendinopathy are warranted.

Pulsed low intensity ultrasound (PLIUS) has been used successfully for bone fracture repair and has therefore been suggested for cartilage regeneration. However, previous in vitro studies with chondrocytes show conflicting results as to the effect of PLIUS on the elaboration of extracellular matrix. This study tests the hypothesis that PLIUS, applied for 20 min/day, stimulates the synthesis of sulphated glycosaminoglycan (sGAG) by adult bovine articular chondrocytes cultured in either monolayer or agarose constructs. For both culture models, PLIUS at either 30 or 100 mW/cm(2) intensity had no net effect on the total sGAG content. Although PLIUS at 100 mW/cm(2) did induce a 20% increase in sGAG content at day 2 of culture in agarose, this response was lost by day 5. Intensities of 200 and 300 mW/cm(2) resulted in cell death probably due to heating from the ultrasound transducers. The lack of a sustained up-regulation of sGAG synthesis may reflect the suggestion that PLIUS only induces a stimulatory effect in the presence of a tissue injury response. These results suggest that PLIUS has a limited potential to provide an effective method of stimulating matrix production as part of a tissue engineering strategy for cartilage repair.

Sustained mechanical loading of skeletal muscle may result in the development of a severe type of pressure ulcer, referred to as deep tissue injury. Recently it was shown that the diffusion of large molecules (10-150 kDa) is impaired during deformation of tissue-engineered skeletal muscle, suggesting a role for impaired diffusion in the aetiology of deep tissue injury. However, the influence of deformation on diffusion of smaller molecules on its aetiology is less clear. This motivated the present study designed to investigate the influence of deformation of skeletal muscle on the diffusion of water, which can be measured with diffusion tensor magnetic resonance imaging (MRI). It could be predicted that this approach will provide valuable information on the diffusion of small molecules. Additionally the relationship between muscle temperature and diffusion was investigated. During deformation of the tibialis anterior a decrease of the apparent diffusion coefficient (ADC) was observed (7.2±3.9%). The use of a finite element model showed that no correlation existed between the maximum shear strain and the decrease of the ADC. The ADC in the uncompressed gastrocnemius muscle decreased with 5.9±3.7%. In an additional experiment a clear correlation was obtained between the decrease of the ADC and the relative temperature change of skeletal muscle tissue as measured by MRI. Taken together, it was concluded that (1) the decreased diffusion of water was not a direct effect of tissue deformation and (2) that it is likely that the observed decreased ADC during deformation was a result of a decreased muscle temperature. The present study therefore provides evidence that diffusion of small molecules, particularly oxygen and carbon dioxide, is not impaired during deformation of skeletal muscle tissue. © 2009 Elsevier Ltd. All rights reserved.

Summary Reasons for performing study: Chondrocytes within articular cartilage respond to the mechanical stresses associated with normal joint loading via a series of signalling pathways. Specific biomolecules, such as nitric oxide (NO), have been implicated in these mechanotransduction processes. It has been shown that the synthesis of NO can be inhibited by dynamic compressive strain of chondrocytes in vitro which, in turn, leads to an up-regulation of specific metabolic parameters. Hypothesis: Chondrocytes isolated from different joint locations and seeded in agarose constructs respond in a distinct manner to the application of dynamic compression. Methods: Chondrocytes were isolated separately from the equine patella groove and the femoral condyle, representing high loaded areas (HLA) and low loaded areas (LLA), respectively, of 6 specimens of different ages. The cells were seeded in agarose constructs and cultured either in an unstrained state or strained under dynamic loading at 1 Hz for 48 h. The synthesis of nitric oxide (NO), proteoglycan synthesis and chondrocyte proliferation were assessed. Results: Equine chondrocytes were found to synthesise significant basal levels of NO, regardless of topographical origin or age of tissue. Marked differences in both proteoglycan synthesis and cell proliferation were, however, revealed between the 2 chondrocyte subpopulations. Dynamic compression inhibited NO synthesis but significant alterations in proteoglycan synthesis and cell proliferation were apparent in a minority of cases. Conclusions and potential relevance: The differential response of the subpopulations of chondrocytes derived from the HLA and LLA provides a potential mechanism which enables the biomechanical demands of differing joint regions to be maintained.

Pressure-related deep tissue injury may develop in skeletal muscle tissue which is subjected to prolonged compression. For early detection, it is important to understand the underlying damage processes. Gawlitta et al. [Gawlitta, D., C. W. J. Oomens, D. L. Bader, F. P. T. Baaijens, and C. V. C. Bouten. Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle. J. Appl. Physiol. 103(2):464-473, 2007b] subjected tissue-engineered muscle constructs to ischemia and deformation to study their effects on viability. Contrary to previous findings, no decrease in viability was found due to compression. However, the nature of their measurement method complicated interpretation of the results, particulary when deformation was involved. Changes in the constructs were assessed by measurements in the surrounding medium. The theoretical model developed in the present study describes metabolism, diffusion, and cell death in the experiments, and accounts for reduced diffusion due to compression. It was demonstrated that the lack of effect of compression on tissue viability, as measured in the experiments, could be explained by the compression-induced decrease in diffusivity. Compression did lead to considerable cell death but this could not be measured by Gawlitta et al. [Gawlitta, D., C. W. J. Oomens, D. L. Bader, F. P. T. Baaijens, and C. V. C. Bouten. Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle. J. Appl. Physiol. 103(2):464-473, 2007b] because diffusion of the cell death marker to the medium was limited. This study shows that a proper description of transport processes is essential for a correct interpretation of experiments in which indirect measurement methods are used. © 2009 The Author(s).

Mechanical stimulus is a regulator of tenocyte metabolism. The present study investigated temporal regulation of the expression of selected genes by tenocytes in isolated fascicles subjected to tensile strain in vitro. Cyclic tensile strain with a 3% amplitude superimposed on a 2% static strain was provided for 10 min, followed by either an unstrained period or continuous cyclic strain until the end of a 24-h incubation period. mRNA expression of selected anabolic and catabolic genes were evaluated with quantitative PCR at 10 min, 1 h, 6 h, and 24 h. The application of 6-h cyclic strain significantly upregulated type III collagen mRNA expression in strained fascicles compared with unstrained controls, but no alterations were observed in mRNA expression of type I collagen and biglycan. Significant downregulation in the expression of the decorin core protein was observed in fascicles subjected to 24-h cyclic strain. MMP3 and MMP13 expression levels were upregulated by the application of 10 min of cyclic strain, followed by a progressive downregulation until the end of the incubation period in both the absence and the presence of the continuing cyclic strain. Accordingly, alterations in the expression of anabolic genes were limited to the upregulation of type III collagen by prolonged exposure to cyclic strain, whereas catabolic genes were upregulated by a small number of strain cycles and downregulated by a prolonged cyclic strain. These findings demonstrate distinctive patterns of mechanoregulation for anabolic and catabolic genes and help our understanding of tenocyte response to mechanical stimulation.

Intermittent pattern of mechanical stimulation has been demonstrated to possess different regulatory effects on cell metabolism in many connective tissues, but little is known about tenocyte responses. A previous study has shown that the application of a small number of continuous cyclic strain inhibited collagen synthesis by tenocytes in explants, whereas a large number of strain cycles upregulated the synthesis. Thus, the present study tested the hypothesis that collagen synthesis is influenced by cyclic tensile strain provided in an intermittent manner. A total of 43,200 cycles of tensile strain, with a 3% amplitude superimposed on a 2% static strain was provided in four different intermittent patterns with different strain/unstrain periods: 10 minutes, 1 hour, 6 hours, and 12 hours. The amount of newly synthesised collagen, both those retained in strained fascicles and released into culture media, were not significantly altered by the application of different patters of intermittent cyclic strain. The present findings may suggest that, unlike other connective tissue cells, tenocyte responses are predominantly regulated by the total number of strain cycles.

To examine whether inhibitors of the MAPK pathways will influence the response of bovine chondrocytes cultured in agarose constructs to IL-1beta and dynamic compression.Dose-response studies were conducted under IL-1beta conditions with either SB203580, SP600125, PDTC or curcumin. In separate experiments, constructs were treated with IL-1beta and an appropriate concentration of inhibitor and subjected to 15% dynamic compression. Nitrite and PGE2 release, 35SO4 and [3H]-thymidine incorporation were subsequently measured using biochemical assays.All inhibitors reduced the IL-1beta induced nitrite and PGE2 release in a dose-dependent manner. The inhibition of [3H]-thymidine incorporation by IL-1beta was partially reversed with SB203580, SP600125 or curcumin, but not PDTC. In most cases, the inhibitors reduced 35SO4 incorporation with IL-1beta. For the mechanical loading studies, the inhibitors reduced the compression-induced inhibition of nitrite and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation.The MAPK, AP-1 and NF-kappaB signalling pathways are involved in the upregulation of NO and PGE2 release by IL-1beta. Dynamic compression stimulates cell proliferation and proteoglycan synthesis in the presence of IL-1beta and/or inhibitors of the MAPKs and NFkappaB and AP-1 signalling pathways. This experimental approach could provide valuable information for the biophysical/pharmacological treatment of OA.

Pressure-related deep tissue injury (DTI) represents a severe pressure ulcer, which initiates in compressed muscle tissue overlying a bony prominence and progresses to more superficial tissues until penetrating the skin. Individual subjects with impaired motor and/or sensory capacities are at high risk of developing DTI. Impaired diffusion of critical metabolites in compressed muscle tissue may contribute to DTI, and impaired diffusion of tissue damage biomarkers may further impose a problem in developing early detection blood tests. We hypothesize that compression of muscle tissue between a bony prominence and a supporting surface locally influences the diffusion capacity of muscle. The objective of this study was therefore, to determine the effects of large compression strains on free diffusion in a tissue-engineered skeletal muscle model. Diffusion was measured with a range of fluorescently labeled dextran molecules (10, 20, 150kDa) whose sizes were representative of both hormones and damage biomarkers. We used fluorescence recovery after photobleaching (FRAP) to compare diffusion coefficients (D) of the different dextrans between the uncompressed and compressed (48-60% strain) states. In a separate experiment, we simulated the effects of local partial muscle ischemia in vivo, by reducing the temperature of compressed specimens from 37 to 34 degrees C. Compared to the D in the uncompressed model system, values in the compressed state were significantly reduced by 47+/-22% (p0.02). A 3 degrees C temperature decrease further reduced D in the compressed specimens by 10+/-6% (p0.05). In vivo, the effects of large strains and ischemia are likely to be summative, and hence, the present findings suggest an important role of impaired diffusion in the etiology of DTI, and should also be considered when developing biochemical screening methods for early detection of DTI.

Deep tissue injury (DTI) is a severe pressure ulcer that results from sustained deformation of muscle tissue overlying bony prominences. In order to understand the etiology of DTI, it is essential to determine the tolerance of muscle cells to large mechanical strains. In this study, a new experimental method of determining the time-dependent critical compressive strains for necrotic cell death (E(zz)(c)(t)) in a planar tissue-engineered construct under static loading was developed. A half-spherical indentor is used to induce a non-uniform, concentric distribution of strains in the construct, and E(zz)(c)(t) is calculated from the radius of the damage region in the construct versus time. The method was employed to obtain E(zz)(c)(t) for bio-artificial muscles (BAMs) cultured from C2C12 murine cells, as a model system for DTI. Specifically, propidium iodine was used to fluorescently stain the development of necrosis in BAMs subjected to strains up to 80%. Two groups of BAMs were tested at an extracellular pH of 7.4 (n=10) and pH 6.5 (n=5). The lowest strain levels causing cell death in the BAMs were determined every 15min, during 285-min-long trials, from confocal microscopy fluorescent images of the size of the damage regions. The experimental E(zz)(c)(t) data fitted a decreasing single-step sigmoid of the Boltzmann type. Analysis of the parameters of this sigmoid function indicated a 95% likelihood that cells could tolerate engineering strains below 65% for 1h, whereas the cells could endure strains below 40% over a 285min trial period. The decrease in endurance of the cells to compressive strains occurred between 1-3h post-loading. The method developed in this paper is generic and suitable for studying E(zz)(c)(t) in virtually any planar tissue-engineered construct. The specific E(zz)(c)(t) curve obtained herein is necessary for extrapolating biological damage from muscle-strain data in biomechanical studies of pressure ulcers and DTI.

In recent years, damage directly due to tissue deformation has gained interest in deep pressure ulcer aetiology research. It has been shown that deformation causes muscle cell damage, though the pathway is unclear. Mechanically induced skeletal muscle damage has often been associated with an increased intracellular Ca2+ concentration, e.g. in eccentric exercise (Allen et al., J Physiol 567(3):723–735, 2005). Therefore, the hypothesis was that compression leads to membrane disruptions, causing an increased Ca2+-influx, eventually leading to Ca2+ overload and cell death. Monolayers of differentiated C2C12 myocytes, stained with a calcium-sensitive probe (fluo-4), were individually subjected to compression while monitoring the fluo-4 intensity. Approximately 50% of the cells exhibited brief calcium transients in response to compression, while the rest did not react. However, all cells demonstrated a prolonged Ca2+ up-regulation upon necrosis, which induced similar up-regulations in some of the surrounding cells. Population heterogeneity is a possible explanation for the observed differences in response, and it might also become important in tissue damage development. It did not become clear however whether Ca2+-influxes were the initiators of damage.

A rat model was used to distinguish between the different factors that contribute to muscle tissue damage related to deep pressure ulcers that develop after compressive loading. In the present study the separate and combined effects of ischemia and deformation were studied. Loading was applied to the hind limb of rats for two hours. Muscle tissue was examined using magnetic resonance imaging (MRI) and histology. An MR-compatible loading device was used, which provided the possibility of simultaneous loading and measurement of tissue status. Two separate loading protocols were applied incorporating uniaxial loading, resulting in compression of the tissue, and ischemic loading. Uniaxial loading was applied to the tibialis anterior (TA) by means of an indenter, and ischemic loading using an inflatable tourniquet. Deformation of the muscle tissue during uniaxial loading was measured using MR tagging. Compression of the tissues for two hours led to increased T2-values, which were correlated to necrotic regions in the TA. Perfusion measurements, using contrast-enhanced MRI, indicated a large ischemic region during indentation. Pure ischemic loading for 2 hours led to reversible tissue changes. From the MR tagging experiments local strain fields were calculated. A deformation of 4.5mm, corresponding to a surface pressure of 150 kPa, resulted in maximum shear strain values up to 1.0. There was a good correlation between the location of damage and the location of high shear strain values. It was concluded that the large deformations, in conjunction with ischemia, provided the main trigger for irreversible muscle damage.

Signals induced by mechanical loading and C-type natriuretic peptide (CNP) represent chondroprotective routes that may potentially prevent osteoarthritis (OA). We examined whether CNP will reduce hyaluronan production and export via members of the multidrug resistance protein (MRP) and diminish pro-inflammatory effects in human chondrocytes. The presence of interleukin-1β (IL-1β) increased HA production and export via MRP5 that was reduced with CNP and/or loading. Treatment with IL-1β conditioned medium increased production of catabolic mediators and the response was reduced with the hyaluronan inhibitor, Pep-1. The induction of pro-inflammatory cytokines by the conditioned medium was reduced by CNP and/or Pep-1, αCD44 or αTLR4 in a cytokine-dependent manner, suggesting that the CNP pathway is protective and should be exploited further.

Item does not contain fulltext BACKGROUND: Individuals who have reduced mobility are at risk of developing pressure ulcers if they are subjected to sustained static postures. To reduce this risk, clinical guidelines advocate healthcare professionals reposition patients regularly. Automated tilting mechanisms have recently been introduced to provide periodic repositioning. This study compared the performance of such a prototype mattress to conventional manual repositioning. METHODS: Ten healthy participants (7 male and 3 female, aged 23-66 years) were recruited to compare the effects of an automated tilting mattress to standard manual repositioning, using the 30 degrees tilt. Measures during the tilting protocols (supine, right and left tilt) included comfort and safety scores, interface pressures, inclinometer angles and transcutaneous gas tensions (sacrum and shoulder). Data from these outcomes were compared between each protocol. FINDINGS: Results indicated no significant differences for either interface pressures or transcutaneous gas responses between the two protocols (P>0.05 in both cases). Indeed a small proportion of participants (~30%) exhibited changes in transcutaneous oxygen and carbon dioxide values in the shoulder during a right tilt for both protocols. The tilt angles at the sternum and the pelvis were significantly less in the automated tilt compared to the manual tilt (mean difference=9.4-11.5 degrees , P

The underlying mechanisms leading to deep tissue injury after sustained compressive loading are not well understood. It is hypothesized that initial damage to muscle fibers is induced mechanically by local excessive deformation. Therefore, in this study, an animal model was used to study early damage after compressive loading to elucidate on the damage mechanisms leading to deep pressure ulcers. The tibialis anterior of Brown-Norway rats was loaded for 2 h by means of an indenter. Experiments were performed in a magnetic resonance (MR)-compatible loading device. Muscle tissue was evaluated with transverse relaxation time (T2)-weighted MRI both during loading and up to 20 h after load removal. In addition, a detailed examination of the histopathology was performed at several time points (1, 4, and 20 h) after unloading. Results demonstrated that, immediately after unloading, T2-weighted MR images showed localized areas with increased signal intensity. Histological examination at 1 and 4 h after unloading showed large necrotic regions with complete disorganization of the internal structure of the muscle fibers. Hypercontraction zones were found bilateral to the necrotic zone. Twenty hours after unloading, an extensive inflammatory response was observed. The proposed relevance of large deformation was demonstrated by the location of damage indicated by T2-weighted MRI and the histological appearance of the compressed tissues. Differences in damage development distal and proximal to the indenter position suggested a contribution of perfusion status in the measured tissue changes that, however, appeared be to reversible.

Chondrocyte mechanotransduction is poorly understood but may involve cell deformation and associated distortion of intracellular structures and organelles. This study quantifies the intracellular displacement and strain fields associated with chondrocyte deformation and in particular the distortion of the mitochondria network, which may have a role in mechanotransduction. Isolated articular chondrocytes were compressed in agarose constructs and simultaneously visualised using confocal microscopy. An optimised digital image correlation technique was developed to calculate the local intracellular displacement and strain fields using confocal images of fluorescently labelled mitochondria. The mitochondria formed a dynamic fibrous network or reticulum, which co-localised with microtubules and vimentin intermediate filaments. Cell deformation induced distortion of the mitochondria, which collapsed in the axis of compression with a resulting loss of volume. Compression generated heterogeneous intracellular strain fields indicating mechanical heterogeneity within the cytoplasm. The study provides evidence supporting the potential involvement of mitochondrial deformation in chondrocyte mechanotransduction, possibly involving strain-mediated release of reactive oxygen species. Furthermore the heterogeneous strain fields, which appear to be influenced by intracellular structure and organisation, may generate significant heterogeneity in mechanotransduction behaviour for cells subjected to identical levels of deformation.

Background: The motion and redistribution of intracellular organelles is a fundamental process in cells. Organelle motion is a complex phenomenon that depends on a large number of variables including the shape of the organelle, the type of motors with which the organelles are associated, and the mechanical properties of the cytoplasm. This paper presents a study that characterizes the diffusive motion of mitochondria in chondrocytes seeded in agarose constructs and what this implies about the mechanical properties of the cytoplasm. Method of approach: Images showing mitochondrial motion in individual cells at 30s intervals for 15min were captured with a confocal microscope. Digital image correlation was used to quantify the motion of the mitochondria, and the mean square displacement (MSD) was calculated. Statistical tools for testing whether the characteristic motion of mitochondria varied throughout the cell were developed. Calculations based on statistical mechanics were used to establish connections between the measured MSDs and the mechanical nature of the cytoplasm. Results: The average MSD of the mitochondria varied with time according to a power law with the power term greater than 1, indicating that mitochondrial motion can be viewed as a combination of diffusion and directional motion. Statistical analysis revealed that the motion of the mitochondria was not uniform throughout the cell, and that the diffusion coefficient may vary by over 50%, indicating intracellular heterogeneity. High correlations were found between movements of mitochondria when they were less than 2μm apart. The correlation is probably due to viscoelastic properties of the cytoplasm. Theoretical analysis based on statistical mechanics suggests that directed diffusion can only occur in a material that behaves like a fluid on large time scales. Conclusions: The study shows that mitochondria in different regions of the cell experience different characteristic motions. This suggests that the cytoplasm is a heterogeneous viscoelastic material. The study provides new insight into the motion of mitochondria in chondrocytes and its connection with the mechanical properties of the cytoplasm.

Although the mechanical behavior of the top layer of the skin, the epidermis, is an important consideration in several clinical and cosmetic applications, there are few reported studies on this layer. The in vivo mechanical behavior of the upper skin layer (here defined as epidermis and papillar dermis) was characterized using a combined experimental and modeling approach. The work was based on the hypothesis that experiments with different length scales represent the mechanical behavior of different skin layers. Suction measurements with aperture diameters of 1, 2 and 6 mm were combined with ultrasound and optical coherence tomography to study the deformation of the skin layers. The experiments were simulated for small displacements with a two-layered finite element model representing the upper layer and the reticular dermis. An identification method compared the experimental and numerical results to identify the material parameters of the model. For one subject the whole parameter estimation procedure was completed, leading to a stiffness of C(10,ul) = 0.11 kPa for the top-layer and C(10,rd) = 0.16 MPa for the reticular dermis. This unexpected, extreme stiffness ratio of the material parameters let to convergence problems of the finite element software for most of the individuals.

Tendon is composed of type I collagen fibers, interspersed with proteoglycan matrix and cells. Glycosaminoglycans may play a role in maintaining the structural integrity of tendon, preventing excessive shearing between collagen components. This study tests the hypothesis that tendon extension mechanisms can be altered by modifying the composition of noncollagenous matrix. Tendon explants were treated with phosphate buffered saline (PBS) or PBS + 0.5 U ml(-1) chondroitinase ABC. Structural changes were examined using TEM and biochemical analysis, while strain response was examined using confocal microscopy and gross mechanical characterization. Chondroitinase ABC removed 90% of glycosaminoglycans from the matrix. Results demonstrated significant swelling of fibrils and surrounding matrix when incubated in either solution. In response to applied strain, PBS incubated samples demonstrated significantly less sliding between adjacent fibers than nonincubated, and a 33% reduction in maximum force. By contrast, fascicles incubated in chondroitinase ABC demonstrated a similar strain response to nonincubated. Data indicate that collagen-proteoglycan binding characteristics can be influenced by incubation and this, in turn, can influence the preferred extension mechanisms adopted by fascicles. This highlights the importance of maintaining fascicles within their natural environment to prevent structural or mechanical changes prior to subsequent analysis.

A combined experimental-numerical approach was adopted to characterize glucose and oxygen uptake and lactate production by bovine articular chondrocytes in a model system. For a wide range of cell concentrations, cells in agarose were supplemented with either low or high glucose medium. During an initial culture phase of 48h, oxygen was monitored noninvasively using a biosensor system. Glucose and lactate were determined by medium sampling. In order to quantify glucose and oxygen uptake, a finite element approach was adopted to describe diffusion and uptake in the experimental model. Numerical predictions of lactate, based on simple relations for cell metabolism, were found to agree well for low glucose, but not for high glucose medium. Oxygen did not play a role in either case. Given the close association between chondrocyte energy metabolism and matrix synthesis, a quantifiable prediction of utilization can present a valuable contribution in the optimization of tissue engineering conditions.

Eukaryotic cells are continuously subjected to mechanical forces under normal physiological conditions. These forces and associated cellular deformations induce a variety of biological processes. The degree of deformation depends on the mechanical properties of the cell. As most cells are anchorage dependent for normal functioning, it is important to study the mechanical properties of cells in their attached configuration. The goal of the present study was to obtain the mechanical and failure properties of attached cells. Individual, attached C2C12 mouse myoblasts were subjected to unconfined compression experiments using a recently developed loading device. The device allows global compression of the cell until cell rupture and simultaneously measures the associated forces. Cell bursting was characterized by a typical reduction in the force, referred to as the bursting force. Mean bursting forces were calculated as 8.7 ± 2.5 μ N at an axial strain of 72 ± 4 %. Visualization of the cell using confocal microscopy revealed that cell bursting was preceded by the formation of bulges at the cell membrane, which eventually led to rupturing of the cell membrane. Finite element calculations were performed to simulate the obtained force–deformation curves. A finite element mesh was built for each cell to account for its specific geometrical features. Using an axisymmetric approximation of the cell geometry, and a Neo–Hookean constitutive model, excellent agreement between predicted and measured force–deformation curves was obtained, yielding an average Young's modulus of 1.14 ± 0.32 kPa .