A review of foot finite element modelling for pressure ulcer prevention in bedrest: Current perspectives and future recommendations.

Pressure ulcers (PUs) are a major public health challenge, having a significant impact on healthcare service and patient quality of life. Computational biomechanical modelling has enhanced PU research by facilitating the investigation of pressure responses in subcutaneous tissue and skeletal muscle. Extensive work has been undertaken on PUs on patients in the seated posture, but research into heel ulcers has been relatively neglected. The aim of this review was to address the key challenges that exist in developing an effective FE foot model for PU prevention and the confusion surrounding the wide range of outputs reported. Nine FE foot studies investigating heel ulcers in bedrest were identified and reviewed. Six studies modelled the posterior part of the heel, two included the calf and foot, and one modelled the whole body. Due to the complexity of the foot anatomy, all studies involved simplification or assumptions regarding parts of the foot structure, boundary conditions and material parameters. Simulations aimed to understand better the stresses and strains exhibited in the heel soft tissues of the healthy foot. The biomechanical properties of soft tissue derived from experimental measurements are critical for developing a realistic model and consequently guiding clinical decisions. Yet, little to no validation was reported in each of the studies. If FE models are to address future research questions and clinical applications, then sound verification and validation of these models is required to ensure accurate conclusions and prediction of patient outcomes. Recommendations and considerations for future FE studies are therefore proposed.

An evaluation of dermal microcirculatory occlusion under repeated mechanical loads: Implication of lymphatic impairment in pressure ulcers.

OBJECTIVE: Pressure ulcers are caused by prolonged mechanical loads deforming the underlying soft tissues. However, the mechanical loads for microcirculatory occlusion are unknown. The present study was designed to characterize the simultaneous response of microvascular and lymphatic structures under repeated mechanical loading. METHODS: The effects of two distinct loading/unloading cycles involving (a) incremental pressures 30, 60, and 90 mmHg and (b) three repeated cycles of 30 mmHg were evaluated on a cohort of able-bodied volunteers. Microvascular response involved the monitoring of transcutaneous gas tensions, while dermal lymphatic activity was estimated from near-infrared imaging. Responses were compared during each load and recovery cycle. RESULTS: Changes in microvascular response were dependent on the load magnitudes, with 30 mmHg resulting in a reduction in oxygen tension only, while 90 mmHg affected both oxygen and carbon dioxide values in most cases (54%). By contrast, lymphatics revealed near total occlusion at 30 mmHg. Although there were intersubject differences, temporal trends consistently revealed partial or full impairment under load, with recovery during off-loading. CONCLUSIONS: The pressure required to cause microcirculatory occlusion differed between individuals, with lymphatic impairment occurring at a lower pressure to that of microvascular vessels. This highlights the need for personalized care strategies and regular off-loading of vulnerable tissues.

Magnetic resonance elastography of skeletal muscle deep tissue injury.

The current state-of-the-art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial-temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury. Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T2 -weighted, and T2 -mapping measurements were performed before, directly after indentation, and at several timepoints during a 14-day follow-up. The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T2 was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T2 . Whereas T2 showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14. In conclusion, we found an initial increase in shear modulus directly after two hours of damage-inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T2 . Since T2 elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T2 for localization of the actual damaged area.

There is an individual tolerance to mechanical loading in compression induced deep tissue injury.

BACKGROUND: Deep tissue injury is a type of pressure ulcer which originates subcutaneously due to sustained mechanical loading. The relationship between mechanical compression and damage development has been extensively studied in 2D. However, recent studies have suggested that damage develops beyond the site of indentation. The objective of this study was to compare mechanical loading conditions to the associated damage in 3D. METHODS: An indentation test was performed on the tibialis anterior muscle of rats (n = 39). Changes in the form of oedema and structural damage were monitored with MRI in an extensive region. The internal deformations were evaluated using MRI based 3D finite element models. FINDINGS: Damage propagates away from the loaded region. The 3D analysis indicates that there is a subject specific tolerance to compression induced deep tissue injury. INTERPRETATION: Individual tolerance is an important factor when considering the mechanical loading conditions which induce damage.

MRI based 3D finite element modelling to investigate deep tissue injury.

Pressure ulcers occur due to sustained mechanical loading. Deep tissue injury is a severe type of pressure ulcer, which is believed to originate in subcutaneous tissues adjacent to bony prominences. In previous experimental-numerical studies the relationship between internal tissue state and damage development was investigated using a 2D analysis. However, recent studies suggest that a local analysis is not sufficient. In the present study we developed a method to create animal-specific 3D finite element models of an indentation test on the tibialis anterior muscle of rats based on MRI data. A detailed description on how the animal specific models are created is given. Furthermore, two indenter geometries are compared and the influence of errors in determining the indenter orientation on the resulting internal strain distribution in a defined volume of tissue was investigated. We conclude that with a spherically-shaped indenter errors in estimating the indenter orientation do not unduly influence the results of the simulation.

An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury.

Early diagnosis of deep tissue injury remains problematic due to the complicated and multifactorial nature of damage induction and the many processes involved in damage development and recovery. In this paper, we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multiparametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multiparametric in vivo MRI, consisting of T2, T2*, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation as well as at several time points during a 14-day follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T2 corresponded with edema, muscle cell damage, and inflammation. T2* was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease was reported on the tissue's microstructural integrity and reflected muscle degeneration and edema as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage-causing event of only 2 h of deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury-related muscle damage. NEW & NOTEWORTHY We have applied a multiparametric MRI approach linked to histopathology to characterize damage development and remodeling in a rat model of deep tissue injury. Our approach provided several relevant insights in deep tissue injury. Response to damage, as observed by MRI, started at some distance from the deformation. Damage after a single indentation period persisted up to 14 days. The MRI parameters provided distinct and complementary information on the microstructural basis of the damage.

The Mechanical Contribution of Vimentin to Cellular Stress Generation.

Contractile stress generation by adherent cells is largely determined by the interplay of forces within their cytoskeleton. It is known that actin stress fibers, connected to focal adhesions, provide contractile stress generation, while microtubules and intermediate filaments provide cells compressive stiffness. Recent studies have shown the importance of the interplay between the stress fibers and the intermediate filament vimentin. Therefore, the effect of the interplay between the stress fibers and vimentin on stress generation was quantified in this study. We hypothesized that net stress generation comprises the stress fiber contraction combined with the vimentin resistance. We expected an increased net stress in vimentin knockout (VimKO) mouse embryonic fibroblasts (MEFs) compared to their wild-type (vimentin wild-type (VimWT)) counterparts, due to the decreased resistance against stress fiber contractility. To test this, the net stress generation by VimKO and VimWT MEFs was determined using the thin film method combined with sample-specific finite element modeling. Additionally, focal adhesion and stress fiber organization were examined via immunofluorescent staining. Net stress generation of VimKO MEFs was three-fold higher compared to VimWT MEFs. No differences in focal adhesion size or stress fiber organization and orientation were found between the two cell types. This suggests that the increased net stress generation in VimKO MEFs was caused by the absence of the resistance that vimentin provides against stress fiber contraction. Taken together, these data suggest that vimentin resists the stress fiber contractility, as hypothesized, thus indicating the importance of vimentin in regulating cellular stress generation by adherent cells.

Adaptation of a MR imaging protocol into a real-time clinical biometric ultrasound protocol for persons with spinal cord injury at risk for deep tissue injury: A reliability study.

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.

Intrinsic Cell Stress is Independent of Organization in Engineered Cell Sheets.

Understanding cell contractility is of fundamental importance for cardiovascular tissue engineering, due to its major impact on the tissue's mechanical properties as well as the development of permanent dimensional changes, e.g., by contraction or dilatation of the tissue. Previous attempts to quantify contractile cellular stresses mostly used strongly aligned monolayers of cells, which might not represent the actual organization in engineered cardiovascular tissues such as heart valves. In the present study, therefore, we investigated whether differences in organization affect the magnitude of intrinsic stress generated by individual myofibroblasts, a frequently used cell source for in vitro engineered heart valves. Four different monolayer organizations were created via micro-contact printing of fibronectin lines on thin PDMS films, ranging from strongly anisotropic to isotropic. Thin film curvature, cell density, and actin stress fiber distribution were quantified, and subsequently, intrinsic stress and contractility of the monolayers were determined by incorporating these data into sample-specific finite element models. Our data indicate that the intrinsic stress exerted by the monolayers in each group correlates with cell density. Additionally, after normalizing for cell density and accounting for differences in alignment, no consistent differences in intrinsic contractility were found between the different monolayer organizations, suggesting that the intrinsic stress exerted by individual myofibroblasts is independent of the organization. Consequently, this study emphasizes the importance of choosing proper architectural properties for scaffolds in cardiovascular tissue engineering, as these directly affect the stresses in the tissue, which play a crucial role in both the functionality and remodeling of (engineered) cardiovascular tissues.

3D Fiber Orientation in Atherosclerotic Carotid Plaques.

Atherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in atherosclerotic plaques for the first time. Seven carotid plaques were imaged ex-vivo with a state-of-the-art Diffusion Tensor Imaging (DTI) technique, using a high magnetic field (9.4Tesla) MRI scanner. A 3D spin-echo sequence with uni-polar diffusion sensitizing pulsed field gradients was utilized for DTI and fiber directions were assessed from diffusion tensor measurements. The distribution of the 3D fiber orientations in atherosclerotic plaques were quantified and the principal fiber orientations (circumferential, longitudinal or radial) were determined. Overall, 52% of the fiber orientations in the carotid plaque specimens were closest to the circumferential direction, 34% to the longitudinal direction, and 14% to the radial direction. Statistically no significant difference was measured in the amount of the fiber orientations between the concentric and eccentric plaque sites. However, concentric plaque sites showed a distinct structural organization, where the principally longitudinally oriented fibers were closer to the luminal side and the principally circumferentially oriented fibers were located more abluminally. The acquired unique information on 3D plaque fiber direction will help understanding pathobiological mechanisms of atherosclerotic plaque progression and pave the road to more realistic biomechanical plaque modeling for rupture assessment.

Cytokine IL1α and lactate as markers for tissue damage in spineboard immobilisation. A prospective, randomised open-label crossover trial.

BACKGROUND: Spinal 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. AIM: In 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. METHODS: Twelve 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-min periods. After each 20-min period, a photo of the buttocks was taken, which was later assessed for redness by two observers. RESULTS: Significant 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. CONCLUSIONS: IL1α 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.

Understanding the requirements of self-expandable stents for heart valve replacement: Radial force, hoop force and equilibrium.

A proper interpretation of the forces developed during stent crimping and deployment is of paramount importance for a better understanding of the requirements for successful heart valve replacement. The present study combines experimental and computational methods to assess the performance of a nitinol stent for tissue-engineered heart valve implantation. To validate the stent model, the mechanical response to parallel plate compression and radial crimping was evaluated experimentally. Finite element simulations showed good agreement with the experimental findings. The computational models were further used to determine the hoop force on the stent and radial force on a rigid tool during crimping and self-expansion. In addition, stent deployment against ovine and human pulmonary arteries was simulated to determine the hoop force on the stent-artery system and the equilibrium diameter for different degrees of oversizing.

A MRI-Compatible Combined Mechanical Loading and MR Elastography Setup to Study Deformation-Induced Skeletal Muscle Damage in Rats.

Deformation of skeletal muscle in the proximity of bony structures may lead to deep tissue injury category of pressure ulcers. Changes in mechanical properties have been proposed as a risk factor in the development of deep tissue injury and may be useful as a diagnostic tool for early detection. MRE allows for the estimation of mechanical properties of soft tissue through analysis of shear wave data. The shear waves originate from vibrations induced by an external actuator placed on the tissue surface. In this study a combined Magnetic Resonance (MR) compatible indentation and MR Elastography (MRE) setup is presented to study mechanical properties associated with deep tissue injury in rats. The proposed setup allows for MRE investigations combined with damage-inducing large strain indentation of the Tibialis Anterior muscle in the rat hind leg inside a small animal MR scanner. An alginate cast allowed proper fixation of the animal leg with anatomical perfect fit, provided boundary condition information for FEA and provided good susceptibility matching. MR Elastography data could be recorded for the Tibialis Anterior muscle prior to, during, and after indentation. A decaying shear wave with an average amplitude of approximately 2 µm propagated in the whole muscle. MRE elastograms representing local tissue shear storage modulus Gd showed significant increased mean values due to damage-inducing indentation (from 4.2 ± 0.1 kPa before to 5.1 ± 0.6 kPa after, p<0.05). The proposed setup enables controlled deformation under MRI-guidance, monitoring of the wound development by MRI, and quantification of tissue mechanical properties by MRE. We expect that improved knowledge of changes in soft tissue mechanical properties due to deep tissue injury, will provide new insights in the etiology of deep tissue injuries, skeletal muscle damage and other related muscle pathologies.

Computationally Designed 3D Printed Self-Expandable Polymer Stents with Biodegradation Capacity for Minimally Invasive Heart Valve Implantation: A Proof-of-Concept Study.

The evolution of minimally invasive implantation procedures and the in vivo remodeling potential of decellularized tissue-engineered heart valves require stents with growth capacity to make these techniques available for pediatric patients. By means of computational tools and 3D printing technology, this proof-of-concept study demonstrates the design and manufacture of a polymer stent with a mechanical performance comparable to that of conventional nitinol stents used for heart valve implantation in animal trials. A commercially available 3D printing polymer was selected, and crush and crimping tests were conducted to validate the results predicted by the computational model. Finally, the degradability of the polymer was assessed via accelerated hydrolysis.

On the importance of 3D, geometrically accurate, and subject-specific finite element analysis for evaluation of in-vivo soft tissue loads.

Pressure ulcers are a type of local soft tissue injury due to sustained mechanical loading and remain a common issue in patient care. People with spinal cord injury (SCI) are especially at risk of pressure ulcers due to impaired mobility and sensory perception. The development of load improving support structures relies on realistic tissue load evaluation e.g. using finite element analysis (FEA). FEA requires realistic subject-specific mechanical properties and geometries. This study focuses on the effect of geometry. MRI is used for the creation of geometrically accurate models of the human buttock for three able-bodied volunteers and three volunteers with SCI. The effect of geometry on observed internal tissue deformations for each subject is studied by comparing FEA findings for equivalent loading conditions. The large variations found between subjects confirms the importance of subject-specific FEA.

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model.

Microneedle arrays have been developed to deliver a range of biomolecules including vaccines into the skin. These microneedles have been designed with a wide range of geometries and arrangements within an array. However, little is known about the effect of the geometry on the potency of the induced immune response. The aim of this study was to develop a computational model to predict the optimal design of the microneedles and their arrangement within an array. The three-dimensional finite element model described the diffusion and kinetics in the skin following antigen delivery with a microneedle array. The results revealed an optimum distance between microneedles based on the number of activated antigen presenting cells, which was assumed to be related to the induced immune response. This optimum depends on the delivered dose. In addition, the microneedle length affects the number of cells that will be involved in either the epidermis or dermis. By contrast, the radius at the base of the microneedle and release rate only minimally influenced the number of cells that were activated. The model revealed the importance of various geometric parameters to enhance the induced immune response. The model can be developed further to determine the optimal design of an array by adjusting its various parameters to a specific situation.

Penetration and delivery characteristics of repetitive microjet injection into the skin.

Drugs can be delivered transdermally using jet injectors, which can be an advantageous route compared to oral administration. However, these devices inject large volumes deep into the skin or tissues underneath the skin often causing bruising and pain. This may be prevented by injecting smaller volumes at lower depth in a repetitive way using a microjet injection device. Such a device could be used to apply drugs in a controllable and sustainable manner. However, the efficacy of microjet injection has been rarely examined. In this study, the penetration and delivery capacity was examined of a repetitive microjet injection device. Various experiments were performed on epidermal and full-thickness ex vivo human as well as ex vivo porcine skin samples. Results revealed that microjets with a velocity exceeding 90m/s penetrated an epidermal skin sample with a delivery efficiency of approximately 96%. In full-thickness human skin, the delivery efficiency drastically decreased to a value of approximately 12%. Experiments on full-thickness skin revealed that the microjets penetrated to a depth corresponding to the transition between the papillary and reticular dermis. This depth did not further increase with increasing number of microjets. In vivo studies on rats indicated that intact insulin was absorbed into the systemic circulation. Hence, the microjet injection device was able to deliver medication into the skin, although the drug delivery efficiency should be increased.

Cell death induced by mechanical compression on engineered muscle results from a gradual physiological mechanism.

Deep tissue injury (DTI), a type of pressure ulcer, arises in the muscle layers adjacent to bony prominences due to sustained mechanical loading. DTI presents a serious problem in the clinic, as it is often not visible until reaching an advanced stage. One of the causes can be direct mechanical deformation of the muscle tissue and cell. The mechanism of cell death induced by mechanical compression was studied using bio-artificial skeletal muscle tissues. Compression was applied by placing weights on top of the constructs. The morphological changes of the cytoskeleton and the phosphorylation of mitogen-activated protein kinases (MAPK) under compression were investigated. Moreover, inhibitors for each of the three major MAPK groups, p38, ERK, and JNK, were applied separately to look at their roles in the compression caused apoptosis and necrosis. The present study for the first time showed that direct mechanical compression activates MAPK phosphorylation. Compression also leads to a gradual destruction of the cytoskeleton. The percentage apoptosis is strongly reduced by p38 and JNK inhibitors down to the level of the unloaded group. This phenomenon could be observed up to 24h after initiation of compression. Therefore, cell death in bio-artificial muscle tissue caused by mechanical compression is primarily caused by a physiological mechanism, rather than through a physical mechanism which kills the cell directly. These findings reveal insight of muscle cell death under mechanical compression. Moreover, the result indicates a potential clinical solution to prevent DTI by pre-treating with p38 or/and JNK inhibitors.

A theoretical compartment model for antigen kinetics in the skin.

The skin is a promising location for vaccination with its abundant population of antigen capturing and presenting cells. The development of new techniques, such as the use of microneedles, can facilitate the delivery of vaccines into the skin. In recent years, many different types of microneedle arrays have been designed. However, their geometry and arrangement within an array may be optimized to trigger sufficient antigen presenting cells. A computational model can support the rational design of microneedle arrays. Therefore, the aim of the current study was to describe the distribution and kinetics of a delivered antigen within the skin using a theoretical compartment model, which included binding of antigens to receptors and their uptake by cells, and to determine which parameters should be measured to validate the model for a specific application. Multiple simulations were performed using a high and low antigen delivery dose and a range of values for the rate constants. The results indicated that the cells were highly saturated when a high dose was applied, while for a low dose saturation was only reached in 5% of the simulations. This was caused by the difference in the ratio between the administered dose and the available binding sites and suggests the dose should be adapted to the number of cells and receptors for a specific compound. The sensitivity analysis of the model parameters confirmed that the initial dose and receptor concentrations were indeed the two parameters that had the largest influence on the variance in antigen concentrations within the cells and circulation at equilibrium. Hence, these parameters are important to be measured in vivo. The presented pharmacokinetics model can be used in future computational models to predict the influence of microneedle array geometry to optimize their design.

A new method to evaluate the effects of shear on the skin.

Currently, pressure ulcer preventive strategies focus mainly on pressure redistribution. Little attention is paid to reduce the harmful effects of shear-force, because little is known about pathophysiological aspects of shear-force. Even today, no method to measure the effects of shear-force on the skin is available. Therefore, the aim of this study was to investigate the response to shear-forces in terms of analyzing a noninvasive biomarker and reactive hyperemic parameter measured at the skin of healthy participants. A physical model was developed to produce a combination of pressure and shear or pressure alone on the skin. Ten healthy male participants were included and pressure (3.9 kPa) and a combined loading of pressure and shear (2.4 kPa + 14.5 N) was applied at the volar aspect of the forearms for 15 and 30 minutes. A Sebutape sample was used to collect IL-1α and total protein (TP) noninvasively. The reactive hyperemic parameter was derived from a laser Doppler flowmeter. The increase in IL-1α/TP-ratio after a combined loading of pressure and shear for 30 minutes of 6.2 ± 2.5 was significantly higher compared with all other test conditions (p < 0.05). The increase in cutaneous blood cell flux was already significantly higher when a combined loading of pressure and shear was applied for 15 minutes compared with pressure alone. These results shows that the IL-1α/TP-ratio and cutaneous blood cell flux can be used as robust measures of the effect of shear-force on skin in humans. Therefore, this model can be used to evaluate materials aimed at the reduction of shear.