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

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

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

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

A model of human skin under large amplitude oscillatory shear.

Skin mechanics is of importance in various fields of research when accurate predictions of the mechanical response of skin is essential. This study aims to develop a new constitutive model for human skin that is capable of describing the heterogeneous, nonlinear viscoelastic mechanical response of human skin under shear deformation. This complex mechanical response was determined by performing large amplitude oscillatory shear (LAOS) experiments on ex vivo human skin samples. It was combined with digital image correlation (DIC) on the cross-sectional area to assess heterogeneity. The skin is modeled as a one-dimensional layered structure, with every sublayer behaving as a nonlinear viscoelastic material. Heterogeneity is implemented by varying the stiffness with skin depth. Using an iterative parameter estimation method all model parameters were optimized simultaneously. The model accurately captures strain stiffening, shear thinning, softening effect and nonlinear viscous dissipation, as experimentally observed in the mechanical response to LAOS. The heterogeneous properties described by the model were in good agreement with the experimental DIC results. The presented mathematical description forms the basis for a future constitutive model definition that, by implementation in a finite element method, has the capability of describing the full 3D mechanical behavior of human skin.