Mechanical Properties Of Skin Research Articles

Visual indentation apparatus and finite element modelling as a method to characterize 3D mechanical properties of facial skin in vivo

Knowledge of the mechanical properties of human skin has essential applications in cosmetic, dermatology and surgical fields. In this study, a hybrid experimental–numerical method was developed to characterize the human skin mechanical properties in vivo. An indentation experiment was physically conducted and simulated by finite element (FE) analysis. In the physical experiment, an indenter made of transparent glass was adopted so that the elliptical eccentricity in the contact area between skin and indenter could be monitored in real-time. In FE simulation, the dermis and subcutaneous tissue were modeled as anisotropic hyperelastic material and isotropic elastic material, respectively. By fitting the FE results to the experimental data, the three-dimensional (3D) mechanical properties of skin, including the dermis and subcutaneous tissue were determined. Furthermore, to demonstrate the ineffectiveness of the hybrid experimental–numerical method, a sensitivity analysis was conducted. In this sensitivity analysis, it is shown that the different mechanical parameters have a different contribution to the final FE result. Finally, the effect of subcutaneous tissue for in vivo skin indentation measurement was also evaluated.

The "Matrisome" reveals the characterization of skin keloid microenvironment.

Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large-scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

A Major QTL is associated with berry grape texture characteristics

Berry texture and berry skin mechanical properties are traits with high agronomic relevance because they are related to quality parameters and marketing requirements of wine, table, and raisin grapes. Searching for QTLs linked to berry texture, an F1 population of 152 individuals and their parents were used in this study. These F1 plants were obtained crossing Raboso Veronese, a seeded black wine grape cultivar, and Sultanina, a seedless white grape variety, especially used for raisins. Density flotation was applied for berry sorting improving the management of many and highly variable genotypes, irrespective of the quantification of specific molecule classes. Berries were evaluated for technological ripeness parameters and mechanical properties. Texture parameters were taken as raw data and as data normalised on berry dimensions, i.e., berry diameter or surface or volume. SSR molecular markers were used to produce a genetic map and a major QTL for berry texture was found on chromosome 18 with traits related to berry firmness showing a phenotypical explained variance higher than 60 %, and traits related to berry resilience, springiness and cohesiveness showing a variance higher than 50 %. Surprisingly, this QTL showed to be associated with SSR markers linked to VviAGL11, the main gene linked to seedlessness. VviAGL11 expression and co-expression profiling during grape ripening was evaluated using available information; this data suggested a role for this gene on the texture of a ripe berry.List of Abbreviations:ABW, average berry weightBR, berry resilienceBR_diam, berry resilience normalised on berry diameterBR_sur, berry resilience normalised on berry surfaceBR_vol, berry resilience normalised on berry volumeBS_ratio, berry springinessBS_ratio_diam, berry springiness normalised on berry diameterBS_ratio_sur, berry springiness normalised on berry surfaceBS_ratio_vol, berry springiness normalised on berry volumeBCo, berry cohesivenessBCo_diam, berry cohesiveness normalised on berry diameterBCo_sur, berry cohesiveness normalised on berry surfaceBCo_vol, berry cohesiveness normalised on berry volumeBH, berry hardnessBH_diam, berry hardness normalised on berry diameterBH_sur, berry hardness normalised on berry surfaceBH_vol, berry hardness normalised on berry volumeBG, berry gumminessBG_diam, berry gumminess normalised on berry diameterBG_sur, berry gumminess normalised on berry surfaceBG_vol, berry gumminess normalised on berry volumeBCh_ratio, berry chewinessBCh_ratio_diam, berry chewiness normalised on berry diameterBCh_ratio_sur, berry chewiness normalised on berry surfaceBCh_ratio_vol, berry chewiness normalised on berry volumeFsk, berry skin break forceWsk, berry skin break energyEsk, berry skin resistance to the axial deformationSpsk, berry skin thickness

Study on nonlinear constitutive model of skin under compression load over a wide range of strain rates

Purpose: In wound ballistics, skin has obvious blocking effect in the biological target penetration of projectiles. An analytical description of skin mechanical properties under compression can set the basis for the numerical simulation and the evaluation of blocking effect. Methods: In this study, an improved three-parameter solid visco-elastic model was proposed to describe the skin creep phenomenon. And then combined with Maxwell and Ogden model, a new nonlinear skin constitutive model, consisting of hyper-elastic unit, creep unit and relaxation unit in parallel, was established. Here, we examine the material properties of freshly harvested porcine skin in compression at strain rates from 0.01/s to 4000/s. Results: The model is verified by comparison with the experimental results by our test and that in the literature at different strain rates. Conclusions: It shows that calculated results of the constitutive model agree well with the experiment data at extremely low to high strain rates, which is useful for the description of the heterogeneous, nonlinear viscoelastic, relaxation and creep mechanical response of skin under compression.

Fourier transform infrared absorption (FTIR) on dry stratum corneum, corneocyte-lipid interfaces: experimental and vibrational spectroscopy calculations

Many questions concerning the biophysical and physiological properties of skin are still open. Skin aging, permeability, dermal absorption, hydration, and drug transdermal delivery, are few examples of processes with unveiled underlying mechanisms. In this work, it is presented a comparison between Fourier transform infrared absorption (FTIR) of dry stratum corneum and stratum corneum under lipase action supported by first-principles density functional vibrational calculations. The molecular structure of stratum corneum was modeled by an archetype of its hygroscopic proteic portion inside the corneocytes, the natural moisturizing factor, coupled to glycerol molecules which represent the lipid fraction of stratum corneum. Vibrational spectra were calculated and compared to experimental data obtained on the animal model of stratum corneum. The experimental results indicated prominent spectral differences between dry and lipase-treated stratum corneum. Principal components analysis and hyerarchical clustering indicated that 1200, 1650, and 1695 cm−1 bands are the most influential on the discrimination. It is noticed that bands in the fingerprint region (800–1800 cm−1) were correctly assigned. Moreover, the calculations revealed the existence of two coupled vibration between the hydroxyl group of lipid and methylene (1120 and 1160 cm−1), which are of special interest since they probe the lipid-amino acid coupling. The model was also able to predict the shear modulus of dry stratum corneum in excellent agreement with the reported values from the literature. Other physical/chemical properties could be calculated exploring the chemical accuracy and molecular resolution of this model. Research in dermatology, cosmetology, and biomedical engineering in the specific topics of drug delivery and/or mechanical properties of skin are examples of fields that would potentially take advantage of this approach.

The relationship between habitual physical activity and skin mechanical properties.

Physical activity (PA) is important for body health. A few reports suggested that PA also influenced skin structure and components. Little data are available on the influence of PA on skin mechanical properties (SMP). Here, we investigated the relationship between PA and SMP. Twenty-five healthy Japanese female subjects (31.0±3.3years) were enrolled in the study. To monitor the 24-hr pulse rate, a wrist watch-type pulse monitor was used. PA intensity was divided into five PA intensity zones (max, anaerobic, aerobic, fat combustion, and warm-up) by the pulse monitor. The average values of the time spent on each intensity for 70days were calculated. To measure SMP, a Cutometer was used at the end of the monitoring. R0 indicated the height of the maximal skin deformation, and R6 was the ratio between viscoelastic and elastic deformation. R0 was positively correlated with the time spent in four of the five PA intensity zones (max, anaerobic, aerobic, and fat combustion), whereas R6 was negatively correlated with the time spent in these four PA intensity zones. The time of warm-up did not correlate with SMP. These results suggest that habitual moderate-to-vigorous PA influences SMP.

Biochemical and physical actions of hyaluronic acid delivered by intradermal jet injection route.

Administration of exogenous hyaluronic acid (HA) by liquid jet injection is considered as a beneficial therapy for dermatology conditions. This paper reviews variety of the factors which would optimize the clinical output of hyaluronic acid in this treatment modality. A pneumatically accelerated jet penetrates the epidermis and spherically spreads micro-droplets of HA in the dermis without significant damage to the tissue and blood vessels. Kinetic energy of the jet activates two parallel mechanisms of action-mechanical and biological-which act synergistically to initiate and augment the regenerative effect. Jet-induced micro-trauma stimulates collagen synthesis and tissue repair without inflammation. Aside from the biophysical stimulation of dermal fibroblast, the biomolecular properties of exogenous HA provide excellent clinical results for skin atrophy, remodeling of dermal scarring, and reverse formation of fibrotic tissue. The effect is mediated by HA-specific cell receptors and depends on molecular weight and the rheological properties of HA polymer. Skin mechanical properties play a key role in predicting HA dispersion patterns. Tolerability and safety of the treatment approach are determined by the jet's physical impact on the tissue and/or by the safety profile of the injected material. Although pneumatic jet delivery of a hyaluronic acid has a limited use in clinical practice, this treatment approach has a strong potential for extended implementation in esthetic dermatology. The synergistic mechanism has significant advantages of predictable and rapid clinical outcomes with a low discomfort. Additional well-designed investigations are required for establishing a scientific foundation and guidelines for this treatment modality.

235 The importance of sirtuins in skin and new findings about sirt2 and its link to mechanobiology

Sirtuins (SIRTs) are a family of NAD+-dependent histone deacetylases that play a critical role in many diverse cellular processes including transcriptional signaling, gene silencing, metabolism, genomic stability, inflammation, energy, stress response and aging. The objectives of this study were to define the temporal role of SIRTs in skin by kinetically quantifying SIRT expression and to assess environmental impact by examining the response to environmental stressors via measuring the effect on energy (ATP) production and oxidative damage (ROS). Additionally, the effect on mechanical properties such as collagen production were measured. Finally, we demonstrate the importance of SIRT2 and its effect on age-induced changes in cell shape. Sirtuin expression levels by Normal Human Epidermal Keratinocytes (NHEK) were measured by RT-PCR. NHEK were exposed to low doses of UVB (10mJ/cm2). Cellular energy (ATP) production as well as oxidative damage (H2O2) were measured. Finally, the effects of SIRTs on pro-collagen type I production in Normal Human Dermal Fibroblasts (NHDF) and cell spreading by aged NHDF were measured. Temporal differences in sirtuin expression levels were observed over time. Furthermore, SIRTs were impacted by environmental stressors such as UVB exposure and ozone, resulting in differences in ATP and H2O2 production. These data show that SIRTs 1,2,3 and 6 support cellular activity necessary for skin mechanical properties such as boosting collagen production and through SIRT-2 increasing cellular-spreading in aging skin cells. SIRTs exhibit temporal expression and are sensitive to environmental stressors. We show that SIRTs are beneficial for both cellular integrity and repair activity. Therefore, supporting their activity is imperative for maintaining optimal skin cell activity.

Performance prediction of Co-injection self-reinforced composites parts based on temperature field

In this paper, polypropylene (PP) was used as raw material to prepare rectangular parts. The temperature change data of the reinforcement with different molding parameters during the filling process were collected by using the injection molding temperature visualization experimental analysis platform. The electronic universal mechanical testing machine (EMUTM) was used for mechanical testing, and the micro-morphology of co-injection self-reinforced composites(CI-SRCs) parts and conventional parts with different temperature fields was observed and analyzed by Polarizing microscope (PLM) and Wide angle X-ray diffraction (WAXD), and the dimensionless equations among four variables (including molding parameters, area ratio of critical temperature field, area ratio of skin layer and mechanical properties) were established. From the results, it was found that the tensile properties of CI-SRCs parts with different molding parameters are superior to that of conventional parts, with a maximum increase of 18.64%. The overall performance of CI-SRCs parts is positively correlated with the performance of the reinforcement, and the performance of reinforcement is mainly determined by the area ratio of skin layer. The difference in the micromorphology characteristics of the parts depends on the change in the temperature field. Therefore, through microscope observation and simulation software analysis, it was obtained that the theoretical critical temperature field forming the orientation skin of the parts was 154.88 °C, and the temperature visualization platform was used to correct the critical temperature field obtained by simulation, and the real critical temperature field was about 170 °C. In the randomized trials, the simulated and actual area ratio of skin layer were in good agreement, with a maximum deviation of 8.9%, which proved that it was reliable to estimate the skin layer area ratio based on theoretical critical temperature field through the change of molding parameters, and then to predict the performance change of the parts.

Influence of Different Dehydration Levels on Volatile Profiles, Phenolic Contents and Skin Hardness of Alkaline Pre-Treated Grapes cv Muscat of Alexandria (Vitis vinifera L.)

A dehydration experiment was carried out on Vitis vinifera L. cv Muscat of Alexandria (synonym Zibibbo) following the process for the production of renowned special dessert wines produced on Pantelleria island (Sicily, Italy). Harvested berries were pre-treated in a sodium hydroxide dipping solution (45 g/L, dipped for 185 s, 25 °C) to accelerate the drying process, rinsed, and dehydrated in simulated conditions (relative humidity 30%, 30 °C temperature, air speed 0.9 m/s). Three dehydration levels were achieved, corresponding to “Passolata”, “Bionda”, and “Malaga” stages (35%, 50%, and 65% of weight loss, respectively) of the Pantelleria denomination of origin (DOC). Grape skin mechanical properties, technological parameters, phenolics, and aroma profile varied considerably during dehydration. The most important aroma compounds for their olfactory impact, such as linalool, geraniol, nerol, and citronellol, especially in glycosylated forms, significantly increased in dried grapes compared to fresh ones, even if aroma profile modification occurred. A decrease in break skin force could have induced higher release of flavonoids. The findings showed relevant changes, allowing winemakers to better select the ratio of fresh and dehydrated grapes in the function of the final desired wine.

Fatty acids based α‐Tocopherol loaded nanostructured lipid carrier gel: In vitro and in vivo evaluation for moisturizing and anti‐aging effects

α-Tocopherol is a potent antioxidant present in the skin. Its concentration decreases with age. Synthetically available α-tocopherol is viscous, irritating to skin and unstable toward oxidation and ultraviolet (UV) light. To develop fatty acids based nanostructured lipid carrier (NLC) gel loaded with α-tocopherol and to evaluate its moisturizing and anti-aging properties. Lauric acid, oleic acid, and Tween-80 were used as solid lipid, liquid lipid, and surfactant, respectively. Seven formulations (F0-F6) were developed by using different concentration of ingredients. Most optimized formulation (F2) was selected for further study on the basis of characterization. Dialysis tube method was used for release study. F2 was incorporated in gel, and then, in vitro and noninvasive in vivo study regarding skin moisture content by corneometer® and skin mechanical properties by cutometer® for 12weeks on human volunteers (n=13) was conducted. Size, polydispersibility index (PDI), zeta potential, and %entrapment efficiency (%EE) of optimized formulation (F2) were found 82nm, 0.261, -28.6, and 94.88±1.16, respectively. Particles were spherical in shape. The release profile showed initial burst and then sustained release, and release data were best fitted to weibull model. α-tocopherol loaded NLC gel (NLCG) appeared physically stable for 12weeks at room temperature and showed significant results in terms of skin capacitance and mechanical properties. Rheological assessment showed non-Newtonian behavior. Fatty acids based NLC proved to be a promising carrier of photochemically unstable lipophilic vitamin E with enhanced moisturizing and anti-aging properties.

From surface microrelief to big wrinkles in skin: A mechanical in-silico model

A major concern associated with skin, the largest organ of our body, is how to prevent it from wrinkling and aging. Understanding the mechanics of skin wrinkling can provide useful insight into skin aging prevention. However, despite decades of endeavors the underlying mechanism of skin wrinkling and aging remains poorly understood. This paper explores the effect of geometrical and mechanical properties of skin on its wrinkling via an integrated theoretical and computational analysis. The skin is modeled with a soft structure having different layers with various thicknesses and material properties. Innovatively, the pattern of skin microrelief is generated and mapped on the model to investigate its effect on the formation of primary lines, secondary lines, and big wrinkles of skin. Analytical interpretation provides preliminary insight into the critical compressive strain for the model skin to start wrinkling, while advanced computational models with surface microrelief offer clues for the skin’s post-wrinkling complex morphology. In particular, tissue geometry, material properties, and microrelief pattern are explored as the determinant parameters to control the location, size, and patterns of skin wrinkles. Our findings allude that the characteristics of compression-induced wrinkles are primarily determined by the geometrical and material property of skin layers rather than the genuine skin microrelief. However, microrelief plays a pivotal role in regulating and determining the locations of primary and secondary wrinkle lines. The edges of the microrelief units are favorable paths for evolving primary and secondary lines. Post-wrinkling analysis reveals that in addition to the periodic sinusoidal pattern, several secondary complex patterns such as non-symmetric periodic, period-doubling and self-contacting folds are observed in the compressed model of skin. Results of the study also show that wrinkle patterns highly depend on the thickness and material property of Stratum Corneum (SC), the outermost layer of skin.

Beneficial effects of food supplements based on hydrolyzed collagen for skin care (Review).

Ageing is a complex, multi-step process which involves, among others loss of collagen and elastin. Collagen is found in large amounts in the body, especially in the dermis layer. These fibers provide the skin's normal strength, hydration and mechanical properties. Collagen is largely available, as it can be extracted from many animal sources, it can be easily absorbed upon topical administration, hence it is largely used in the cosmetic and pharmaceutical industry for the treatment of premature aging. Bioactive peptides, such as collagen hydrolyzate, are among the most used ingredients for the development of nutraceuticals - food or food ingredients that have defined physiological effects. Numerous studies have demonstrated that peptides resulted from ingestion of hydrolysate collagen and detected in the blood stream have chemotactic properties for skin fibroblasts, helping the skin restoration process. The purpose of this minireview is to present an update on the use of hydrolyzed collagen for skin care.

The regional-dependent biaxial behavior of young and aged mouse skin: A detailed histomechanical characterization, residual strain analysis, and constitutive model

Skin fulfills several vital functions, many of which are dependent on its mechanical properties. Therefore, as mice have become an invaluable model for skin research, determining murine skin's mechanical properties is important. Specifically, skin's mechanical properties are important for functional tests as well as for prognostic and diagnostic purposes. Additionally, computational simulations of skin behavior are becoming commonplace, rendering accurate models of murine skin's constitutive behavior necessary. To date, our knowledge of mouse skin mechanics shows significant gaps. For example, there are no comprehensive reports correlating skin's mechanical properties with region, age, and direction. Moreover, mouse skin's residual strain behavior has not been reported on. In our current work, we set out to fill these gaps. Based on histology, 2-photon microscopy, and planar biaxial testing, while accurately tracking various reference configurations, we report on differences in gross structure, microstructural organization, and constitutive response of skin, and cast those properties into a versatile Fung-type hyperelastic constitutive law for three reference configurations. Our data is the most comprehensive report contrasting the mechanical properties of young (12 weeks) and aged (52 weeks) mouse skin and will, thus, be valuable to basic science as control data, and provide accurate constitutive laws for mouse skin modeling. Statement of significanceOur findings are significant as they fill several gaps in our understanding of mouse skin mechanics. This is particularly important as mouse skin is becoming a frequent and critical model of human skin for cosmetic and medical science. Specifically, we quantified how mechanical properties of mice skin vary with age, with location, and with direction. Additionally, we cast our findings into constitutive models that can be used by others for predictive computer simulations of skin behavior.

Defining age-related skin tears: a review

Skin tears are reported to be the most common wound found amongst elderly individuals, yet there is a lack of evidence and consensus on a definition for these age-related traumatic injuries. A consensus on definition is essential for benchmarking prevalence and incidence and informing clinical diagnosis, management and reporting. This paper examines the extent of similarity and heterogeneity between the published definitions of skin tears and the underpinning evidence for the same. Five criteria were used to evaluate and compare the published skin tear definitions – reference to skin pathology; cause of injury; effect of injury; site of injury; and reference to the population group being studied. As a result of the review and recent research findings, which explicitly demonstrate age-related changes to the structural and mechanical properties of skin and associated increased risk of skin tears, the authors present a new skin tear definition based on these findings. Skin tears are defined as trauma-induced partial or full thickness wounds which primarily occur on the extremities of older persons with age-related changes to the skin’s structural and mechanical support properties, and are commonly associated with elastosis and/or ecchymosis.

Controlled mechanical vibration and impacts on skin biology.

Different biological models have shown how mechanical stimulation may induce physiological responses from solicited cells, tissues, or organs. In models of cultured skin cells, the frequency of the mechanical stress appears to be a paramount parameter, generating a biological response in some cells, particularly from dermal fibroblasts. Our objective was to explore in ex vivo human skin explants the effects of mechanical stimulation. Mechanical stimulations were provided by a torque test device, with different end effectors, able to generate cyclic strains at different frequencies (from 40 to 120Hz). Skin explant samples were stimulated twice daily by the device for one minute, over 10days. At days 0, 5, and 10, samples were processed by immunohistological procedures, allowing some structural dermal proteins to be quantified (fluorescence). As compared to untreated skin explant samples, the stimulation procedure clearly led some proteins of the dermal-epidermal and some dermal proteins to be overexpressed. This stimulation was found to be frequency-dependent, with the greatest overall increases occurring at 60 and 90Hz. For the first time, ultrafast ultrasound imaging in vitro (phantom mimicking skin mechanical properties) was used to analyze mechanical waves transmitted to the skin layers as a function of end effector shape.

A microstructurally inspired constitutive model for skin mechanics.

This study investigates the link between the mechanical properties of skin and its microstructural characteristics. Rat back skin samples from different locations, orientations, and sexes were collected and subjected to quasi-static uniaxial tensile tests. Stress-stretch behavior at low stress ranges and rupture data at high stress ranges were collected. The influence of location, orientation, and sex on skin mechanical properties was examined by comparing the mechanical parameters (i.e., initial slope, maximum slope, ultimate tensile strength, rupture stretch, and toughness) evaluated from the tensile testing data. Location and orientation were both found to have a significant effect on the mechanical properties. Collagen structural data (i.e., fiber orientation distribution, relative content, and fiber straightness) were evaluated using histology images. It was found that the rat lower (caudal) back had higher relative collagen content when compared to the upper (cranial) back. A microstructurally based constitutive model was proposed to describe the mechanical behavior of preconditioned rat back skin. The constitutive model incorporated the distribution of collagen fiber bundle orientations and relative collagen content measured from histology, and showed good agreement with the tensile test data. The influence of location and orientation was also evident in the optimized constitutive parameters. This study was a comprehensive investigation that combines skin mechanical behavior, micro-structure, and constitutive modeling.

CCN1 expression by fibroblasts is required for bleomycin-induced skin fibrosis

The microenvironment contributes to the excessive connective tissue deposition that characterizes fibrosis. Members of the CCN family of matricellular proteins are secreted by fibroblasts into the fibrotic microenvironment; however, the role of endogenous CCN1 in skin fibrosis is unknown. Mice harboring a fibroblast-specific deletion for CCN1 were used to assess if CCN1 contributes to dermal homeostasis, wound healing, and skin fibrosis. Mice with a fibroblast-specific CCN1 deletion showed progressive skin thinning and reduced accumulation of type I collagen; however, the overall mechanical property of skin (Young's modulus) was not significantly reduced. Real time-polymerase chain reaction analysis revealed that CCN1-deficient skin displayed reduced expression of mRNAs encoding enzymes that promote collagen stability (including prolyl-4-hydroxylase and PLOD2), although expression of COL1A1 mRNA was unaltered. CCN1-deficent skin showed reduced hydroxyproline levels. Electron microscopy revealed that collagen fibers were disorganized in CCN1-deficient skin. CCN1-deficient mice were resistant to bleomycin-induced skin fibrosis, as visualized by reduced collagen accumulation and skin thickness suggesting that deposition/accumulation of collagen is impaired in the absence of CCN1. Conversely, CCN1-deficient mice showed unaltered wound closure kinetics, suggesting de novo collagen production in response to injury did not require CCN1. In response to either wounding or bleomycin, induction of α-smooth muscle actin-positive myofibroblasts was unaffected by loss of CCN1. CCN1 protein was overexpressed by dermal fibroblasts isolated from lesional (i.e., fibrotic) areas of patients with early onset diffuse scleroderma. Thus, CCN1 expression by fibroblasts, being essential for skin fibrosis, is a viable anti-fibrotic target.

The Regional-Dependent Biaxial Behavior of Aging Mouse Skin: A Detailed Histomechanical Characterization, Residual Strain Analysis, and Constitutive Model

Skin fulfills a number of vital functions, many of which are dependent on its mechanical properties. Therefore, as mice have become an invaluable model for skin research, determining murine skin's mechanical properties is important. Specifically, skin's mechanical properties are important for functional tests as well as for prognostic and diagnostic purposes. Additionally, computational simulations of skin behavior are becoming commonplace, rendering accurate models of murine skin's constitutive behavior necessary. To date, our knowledge of mouse skin mechanics shows significant gaps. For example, there are no comprehensive reports correlating skin's mechanical properties with region, age, and direction. Moreover, mouse skin's residual strain behavior has not been reported on. In our current work, we set out to fill these gaps. Based on histology, 2-photon microscopy, and planar biaxial testing, while accurately tracking various reference configurations, we report on differences in gross structure, microstructural organization, and constitutive response of skin, and cast those properties into a versatile Fung-type hyperelastic constitutive law for three reference configurations. Our data is the most comprehensive report on the mechanical properties of mouse skin and will, thus, be valuable to basic science, as control data, and provide accurate constitutive laws for mouse skin modeling.

Linking microvascular collapse to tissue hypoxia in a multiscale model of pressure ulcer initiation.

Pressure ulcers are devastating injuries that disproportionately affect the older adult population. The initiating factor of pressure ulcers is local ischemia, or lack of perfusion at the microvascular level, following tissue compression against bony prominences. In turn, lack of blood flow leads to a drop in oxygen concentration, i.e, hypoxia, that ultimately leads to cell death, tissue necrosis, and disruption of tissue continuity. Despite our qualitative understanding of the initiating mechanisms of pressure ulcers, we are lacking quantitative knowledge of the relationship between applied pressure, skin mechanical properties as well as structure, and tissue hypoxia. This gap in our understanding is, at least in part, due to the limitations of current imaging technologies that cannot simultaneously image the microvascular architecture, while quantifying tissue deformation. We overcome this limitation in our work by combining realistic microvascular geometries with appropriate mechanical constitutive models into a microscale finite element model of the skin. By solving boundary value problems on a representative volume element via the finite element method, we can predict blood volume fractions in response to physiological skin loading conditions (i.e., shear and compression). We then use blood volume fraction as a homogenized variable to couple tissue-level skin mechanics to an oxygen diffusion model. With our model, we find that moderate levels of pressure applied to the outer skin surface lead to oxygen concentration contours indicative of tissue hypoxia. For instance, we show that applying a pressure of 60kPa at the skin surface leads to a decrease in oxygen partial pressure from a physiological value of 65mmHg to a hypoxic level of 31mmHg. Additionally, we explore the sensitivity of local oxygen concentration to skin thickness and tissue stiffness, two age-related skin parameters. We find that, for a given pressure, oxygen concentration decreases with decreasing skin thickness and skin stiffness. Future work will include rigorous calibration and validation of this model, which may render our work an important tool toward developing better prevention and treatment tools for pressure ulcers specifically targeted toward the older adult patient population.