Aim Pressure-ulcer occurrence in the seated patient is understudied. Preventative devices have been developed and are prescribed commonly, but there is little quantitative evidence of their effectiveness. This study explores the concept of a lateral pressure device, a prevention device that applies pressure to the sides of the seated buttocks, to reduce the amount of tissue distortion and blood-vessel occlusion. It is hypothesized that this device will reduce deep tissue injury by reducing the pressure at the bone-muscle interface, as demonstrated computationally in previous research. This study aimed to use oximetry to investigate the efficacy of the device in maintaining transcutaneous gas tensions of the tissue as close to baseline as possible. Methods Oximetry electrodes were attached to participants’ ischial tuberosity and greater trochanter for different amounts of lateral pressure. The amount of lateral pressure is a given percentage of the pressure due to the participants’ underbody pressure. Results The results show that 50% lateral pressure is sufficient to produce an improvement in participants’ gas tensions at their ischial tuberosity, without negatively impacting the tissue at their greater trochanter, relative to the control of sitting with no application of lateral pressure. Conclusion Despite a rudimentary prototype device design, and that participants each placed their own oximetry sensors, results support the application of lateral pressure as a method to maintain transcutaneous gas tensions. Further work should be carried out on a larger sample to consolidate these findings.

Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full-thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that hair follicle tranplantation induced an increase in the epidermal thickness, interdigitation of the epidermal-dermal junction, dermal cell density, and blood vessel density. Remodelling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibres, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro-fibrotic factors TGFβ1, IL13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars.

The elephant’s trunk is multifunctional: It must be flexible to wrap around vegetation, but tough to knock down trees and resist attack. How can one appendage satisfy both constraints? In this combined experimental and theoretical study, we challenged African elephants to reach far-away objects with only horizontal extensions of their trunk. Surprisingly, the trunk does not extend uniformly, but instead exhibits a dorsal “joint” that stretches 15% more than the corresponding ventral section. Using material testing with the skin of a deceased elephant, we show that the asymmetry is due in part to patterns of the skin. The dorsal skin is folded and 15% more pliable than the wrinkled ventral skin. Skin folds protect the dorsal section and stretch to facilitate downward wrapping, the most common gripping style when picking up items. The elephant’s skin is also sufficiently stiff to influence its mechanics: At the joint, the skin requires 13 times more energy to stretch than the corresponding length of muscle. The use of wrinkles and folds to modulate stiffness may provide a valuable concept for both biology and soft robotics.

Skin injuries remain a persistent problem for users of lower-limb prostheses despite sustained progress in prosthesis design. One factor limiting the prevention of skin injuries is that skin on the residual limb is not suited to bear the mechanical loads of ambulation. One part of the body that is suited to this task is the sole of the foot. Here, we propose a novel strategy to actively augment skin's tolerance to load, increasing its resistance to mechanically induced injuries. We hypothesise that the load tolerance of skin can be augmented by autologous transplantation of plantar fibroblasts into the residual limb dermis. We expect that introducing plantar fibroblasts will induce the overlying keratinocytes to express plantar-specific keratins leading to a tougher epidermis. Using a computational finite element model of a weight-bearing residual limb, we estimate that skin deformation (a key driver of pressure ulcer injuries) could be halved by reprogramming skin to a plantar-like phenotype. We believe this strategy could yield new progress in pressure ulcer prevention for amputees, facilitating rehabilitation and improving quality of life for patients.

When immobile or neuropathic patients are supported by beds or chairs, their soft tissues undergo deformations that can cause pressure ulcers. Current support surfaces that redistribute under-body pressures at vulnerable body sites have not succeeded in reducing pressure ulcer prevalence. Here we show that adding a supporting lateral pressure can counter-act the deformations induced by under-body pressure, and that this 'pressure equalisation' approach is a more effective way to reduce ulcer-inducing deformations than current approaches based on redistributing under-body pressure. A finite element model of the seated pelvis predicts that applying a lateral pressure to the soft tissue reduces peak von Mises stress in the deep tissue by a factor of 2.4 relative to a standard cushion (from 113 kPa to 47 kPa)-a greater effect than that achieved by using a more conformable cushion, which reduced von Mises stress to 75 kPa. Combining both a conformable cushion and lateral pressure reduced peak von Mises stresses to 25 kPa. The ratio of peak lateral pressure to peak under-body pressure was shown to regulate deep tissue stress better than under-body pressure alone. By optimising the magnitude and position of lateral pressure, tissue deformations can be reduced to that induced when suspended in a fluid. Our results explain the lack of efficacy in current support surfaces and suggest a new approach to designing and evaluating support surfaces: ensuring sufficient lateral pressure is applied to counter-act under-body pressure.

BACKGROUND:Abnormal fetal movements are implicated in joint pathologies such as arthrogryposis and developmental dysplasia of the hip (DDH). Experimentally induced paralysis disrupts joint cavitation and morphogenesis leading to postnatal abnormalities. However, the developmental window(s) most sensitive to immobility-and therefore the best time for intervention-have never been identified. Here, we systematically vary the timing and duration of paralysis during early chick hip joint development. We then test whether external manipulation of immobilized limbs can mitigate the effects of immobility.RESULTS:Timing of paralysis affected the level of disruption to joints, with paralysis periods between embryonic days 4 and 7 most detrimental. Longer paralysis periods produced greater disruption in terms of failed cavitation and abnormal femoral and acetabular geometry. External manipulation of an immobilized limb led to more normal morphogenesis and cavitation compared to un-manipulated limbs.CONCLUSIONS:Temporary paralysis is detrimental to joint development, particularly during days 4 to 7. Developmental processes in the very early stages of joint development may be critical to DDH, arthrogryposis, and other joint pathologies. The developing limb has the potential to recover from periods of immobility, and external manipulation provides an innovative avenue for prevention and treatment of developmental joint pathologies.

Our sense of fine touch deteriorates as we age, a phenomenon typically associated with neurological changes to the skin. However, geometric and material changes to the skin may also play an important role on tactile perception and have not been studied in detail. Here, a finite element model is utilised to assess the extent to which age-related structural changes to the skin influence the tactile stimuli experienced by the mechanoreceptors. A numerical, hyperelastic, four-layered skin model was developed to simulate sliding of the finger against a rigid surface. The strain, deviatoric stress and strain energy density were recorded at the sites of the Merkel and Meissner receptors, whilst parameters of the model were systematically varied to simulate age-related geometric and material skin changes. The simulations comprise changes in skin layer stiffness, flattening of the dermal-epidermal junction and thinning of the dermis. It was found that the stiffness of the skin layers has a substantial effect on the stimulus magnitudes recorded at mechanoreceptors. Additionally, reducing the thickness of the dermis has a substantial effect on the Merkel disc whilst the Meissner corpuscle is particularly affected by flattening of the dermal epidermal junction. In order to represent aged skin, a model comprising a combination of ageing manifestations revealed a decrease in stimulus magnitudes at both mechanoreceptor sites. The result from the combined model differed from the sum of effects of the individually tested ageing manifestations, indicating that the individual effects of ageing cannot be linearly superimposed. Each manifestation of ageing results in a decreased stimulation intensity at the Meissner Corpuscle site, suggesting that ageing reduces the proportion of stimuli meeting the receptor amplitude detection threshold. This model therefore offers an additional biomechanical explanation for tactile perceptive degradation amongst the elderly. Applications of the developed model are in the evaluation of cosmetics products aimed at mitigating the effects of ageing, e.g. through skin hydration and administration of antioxidants, as well as in the design of products with improved tactile sensation, e.g. through the optimisation of materials and surface textures.

In skin homeostasis, dermal fibroblasts are responsible for coordinating the migration and differentiation of overlying epithelial keratinocytes. As hairy skin heals faster than nonhairy skin, we took bio-inspiration from the follicle and hypothesized that follicular fibroblasts would accelerate skin re-epithelialization after injury faster than interfollicular fibroblasts. Using both in vitro and ex vivo models of human skin wound closure, we found that hair follicle dermal papilla fibroblasts could accelerate closure of in vitro scratch wounds by 1.8-fold and epithelial growth capacity by 1.5-fold compared with controls (P < 0.05). We used a cytokine array to determine how the dermal papilla fibroblasts were eliciting this effect and identified two cytokines, sAXL and CCL19, that are released at significantly higher levels by follicular fibroblasts than by interfollicular subtypes. Using sAXL and CCL19 individually, we found that they could also increase closure of epithelial cells in a scratch wound by 1.2- and 1.5-fold, respectively, compared with controls (P < 0.05). We performed an unbiased transcriptional analysis, combined with pathway analysis, and postulate that sAXL accelerates wound closure by promoting migration and inhibiting epithelial differentiation of skin keratinocytes. Long term, we believe these results can be exploited to accelerate wound closure of human skin in vivo.

Plantar skin on the soles of the feet has a distinct morphology and composition that is thought to enhance its tolerance to mechanical loads, although the individual contributions of morphology and composition have never been quantified. Here, we combine multiscale mechanical testing and computational models of load bearing to quantify the mechanical environment of both plantar and nonplantar skin under load. We find that morphology and composition play distinct and complementary roles in plantar skin’s load tolerance. More specifically, the thick stratum corneum provides protection from stress-based injuries such as skin tears and blisters, while epidermal and dermal compositions provide protection from deformation-based injuries such as pressure ulcers. This work provides insights into the roles of skin morphology and composition more generally and will inform the design of engineered skin substitutes as well as the etiology of skin injury.

Many cardiovascular diseases are characterised by the restriction of blood flow through arteries. Stents can be expanded within arteries to remove such restrictions; however, tissue in-growth into the stent can lead to restenosis. In order to predict the long-term efficacy of stenting, a mechanobiological model of the arterial tissue reaction to stress is required. In this study, a computational model of arterial tissue response to stenting is applied to three clinically relevant stent designs. We ask the question whether such a mechanobiological model can differentiate between stents used clinically, and we compare these predictions to a purely mechanical analysis. In doing so, we are testing the hypothesis that a mechanobiological model of arterial tissue response to injury could predict the long-term outcomes of stent design. Finite element analysis of the expansion of three different stent types was performed in an idealised, 3D artery. Injury was calculated in the arterial tissue using a remaining-life damage mechanics approach. The inflammatory response to this initial injury was modelled using equations governing variables which represented tissue-degrading species and growth factors. Three levels of inflammation response were modelled to account for inter-patient variability. A lattice-based model of smooth muscle cell behaviour was implemented, treating cells as discrete agents governed by local rules. The simulations predicted differences between stent designs similar to those found in vivo. It showed that the volume of neointima produced could be quantified, providing a quantitative comparison of stents. In contrast, the differences between stents based on stress alone were highly dependent on the choice of comparison criteria. These results show that the choice of stress criteria for stent comparisons is critical. This study shows that mechanobiological modelling may provide a valuable tool in stent design, allowing predictions of their long-term efficacy. The level of inflammation was shown to affect the sensitivity of the model to stent design. If this finding was verified in patients, this could suggest that high-inflammation patients may require alternative treatments to stenting.

One way to restore physiological blood flow to occluded arteries involves the deformation of plaque using an intravascular balloon and preventing elastic recoil using a stent. Angioplasty and stent implantation cause unphysiological loading of the arterial tissue, which may lead to tissue in-growth and reblockage; termed "restenosis." In this paper, a computational methodology for predicting the time-course of restenosis is presented. Stress-induced damage, computed using a remaining life approach, stimulates inflammation (production of matrix degrading factors and growth stimuli). This, in turn, induces a change in smooth muscle cell phenotype from contractile (as exists in the quiescent tissue) to synthetic (as exists in the growing tissue). In this paper, smooth muscle cell activity (migration, proliferation, and differentiation) is simulated in a lattice using a stochastic approach to model individual cell activity. The inflammation equations are examined under simplified loading cases. The mechanobiological parameters of the model were estimated by calibrating the model response to the results of a balloon angioplasty study in humans. The simulation method was then used to simulate restenosis in a two dimensional model of a stented artery. Cell activity predictions were similar to those observed during neointimal hyperplasia, culminating in the growth of restenosis. Similar to experiment, the amount of neointima produced increased with the degree of expansion of the stent, and this relationship was found to be highly dependant on the prescribed inflammatory response. It was found that the duration of inflammation affected the amount of restenosis produced, and that this effect was most pronounced with large stent expansions. In conclusion, the paper shows that the arterial tissue response to mechanical stimulation can be predicted using a stochastic cell modeling approach, and that the simulation captures features of restenosis development observed with real stents. The modeling approach is proposed for application in three dimensional models of cardiovascular stenting procedures.

The design of medical devices could be very much improved if robust tools were available for computational simulation of tissue response to the presence of the implant. Such tools require algorithms to simulate the response of tissues to mechanical and chemical stimuli. Available methodologies include those based on the principle of mechanical homeostasis, those which use continuum models to simulate biological constituents, and the cell-centred approach, which models cells as autonomous agents. In the latter approach, cell behaviour is governed by rules based on the state of the local environment around the cell; and informed by experiment. Tissue growth and differentiation requires simulating many of these cells together. In this paper, the methodology and applications of cell-centred techniques—with particular application to mechanobiology—are reviewed, and a cell-centred model of tissue formation in the lumen of an artery in response to the deployment of a stent is presented. The method is capable of capturing some of the most important aspects of restenosis, including nonlinear lesion growth with time. The approach taken in this paper provides a framework for simulating restenosis; the next step will be to couple it with more patient-specific geometries and quantitative parameter data.

One of the most significant limitations of percutaneous coronary intervention using stents is the growth of tissue within the stent, leading to re-occlusion of the target vessel. There is a wide range of stents available, and stent designs differ in their efficacy [1]. Stent parameters such as stent length, strut configuration, diameter and expansion method have been shown to influence the amount of restenosis provoked [2]. Despite many generations of coronary stents — and the advent of drug elution — up to 10% of percutaneous coronary interventions require revision, climbing to 50% in some high risk lesions [3].

In composite arterial coronary grafts (CACGs), transport phenomena and geometry may considerably alter blood flow dynamics. CACGs aim at revascularizing pathological arteries according to the human anatomy. However, the exact mechanisms causing the failure of coronary bypass grafting are not yet well elucidated. In the present study, computational fluid dynamics (CFD) techniques are applied for the simulation of multi-branched CACGs under physiologically realistic inflow waveforms. The numerical solution is obtained by a finite-volume method formulated in non-orthogonal, curvilinear coordinates and a multi-grid approach. The geometrical models, consisting of idealized and rigid vessels, include the typical T- and a rather new Π-graft configuration. The stenotic effect is also investigated by comparing computational results for three different degrees of area constriction, namely 25%, 50% and 75%, as well as the case without stenosis. Different grafting distances and various inflow rate ratios are imposed, to give an insight into haemodynamical alterations of CACGs and to study the process of restenosis. The results focus on the interaction between the grafts and coronary flows in terms of spatial and temporal variations of velocity and wall shear stress (WSS) distribution. Prominent variations among the different geometries, concerning the velocity profiles and secondary flow motion, are shown. Moreover, the residual flow emerging from different degrees of area constriction shows that low and oscillating shear stresses may arise for even moderate stenotic fields.