Cees W.J. Oomens’s research while affiliated with Eindhoven University of Technology and other places

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 with 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 better understand 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.

Background The heel is one of the most common sites of pressure ulcers and the anatomical location with the highest prevalence of deep tissue injury. Several finite element modeling studies investigate heel ulcers for bedridden patients. In the current study we have added the implementation of the calf structure to the current heel models. We tested the effect of foot posture, mattress stiffness, and a lateral calcaneus displacement to the contact pressure and internal maximum shear strain occurring at the heel. Methods A new 3D finite element model is created which includes the heel and calf structure. Sensitivity analyses are performed for the foot orientation relative to the mattress, the Young's modulus of the mattress, and a lateral displacement of the calcaneus relative to the other soft tissues in the heel. Findings The models predict that a stiffer mattress results in higher contact pressures and internal maximum shear strains at the heel as well as the calf. An abducted foot posture reduces the internal strains in the heel and a lateral calcaneus displacement increases the internal maximum shear strains. A parameter study with different mattress-skin friction coefficients showed that a coefficient below 0.4 decreases the maximum internal shear strains in all of the used loading conditions. Interpretation In clinical practice, it is advised to avoid internal shearing of the calcaneus of patients, and it could be taken into consideration by medical experts and nurses that a more abducted foot position may reduce the strains in the heel.

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.

p>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.</p

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.

The need to provide an objective robust indicator of early mechanically induced damage of soft tissues, particularly in those individual considered to be at risk of developing pressure ulcers. Although physical sensors have proved useful in assessing tissue viability or status, they do not represent a simple and inexpensive solution, which could be easily translated into a range of clinical settings. Biomarkers have been introduced to assess the status of a number of tissues/organs in diseased states. Their potential use in the early detection of pressure ulcer development has been recently proposed in a number of studies. This chapter describes a range of alternative approaches involving simple methods to collect biomarkers released from the outer layers of skin, sweat and body fluids, such as blood and urine. A range of biomarkers have been evaluated involving pro-inflammatory cytokines released by the mechanical irritation of skin, metabolic markers indicative of anaerobic respiration and degradation products of skin and muscle. Specific limitations of these approaches have been highlighted including limited sample volumes, low concentration levels and the temporal profiles and interaction of the biomarkers, each of which can be overcome with current analytical tools, sensing technologies and well designed test protocols. The authors believe that biosensing systems will soon be available to detect biomarkers which are indicative of early damage in loaded soft tissues.

Early diagnosis of deep tissue injury remains problematic due to the complicated and multi-factorial 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 multi-parametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multi-parametric 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 days 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 T2corresponded with edema, muscle cell damage, and inflammation. T2∗ was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease reported on the tissue's microstructural integrity and reflected muscle degeneration, 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 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.

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 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 the 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 (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.

Cambridge Core - Biomedical Engineering - Biomechanics - by Cees Oomens

The skin is the largest organ of the human body. With its layered structure, it is mechanically a very complicated tissue. From the outer surface down, the main layers are the stratum corneum (10–15 μm), the viable epidermis (100–150 μm), dermis (subdivided into the papillary and reticular dermis, ≈2 mm), and hypodermis. Although the stratum corneum is part of the epidermis, it is often considered to be a separate layer because of its specific barrier properties. It consists of nonviable cells and is very firm, but pliable and wrinkled. The epidermis is mainly composed of cells migrating to the skin surface. When the cells are closer to the stratum corneum, they become more keratinized. The viable epidermis has an undulated geometry. This undulation becomes less with age. The dermis is largely composed of a very dense network of collagen and elastin fibers, dominating the mechanical behavior of the total skin. The deepest skin layer, the hypodermis or subcutaneous adipose tissue, is composed of loose fatty connective tissue. The dermis contains microstructures such as blood vessels, lymph vessels, nerve endings, sweat glands, hair follicles, and different cell types. The influence of the different layers on the mechanical properties has often been ignored, because authors are mainly interested in the bulk mechanical behavior, dominated by the main components of the skin layer.