A theoretical analysis of damage evolution in skeletal muscle tissue with reference to pressure ulcer development.

Soft tissues are sensitive to prolonged compressive loading, eventually leading to tissue necrosis in the form of pressure ulcers [1]. Pressure ulcers can occur in situations where people are subjected to sustained mechanical loads, such as when bedridden, sitting in a wheelchair or from wearing prostheses. Pressure ulcers severely affect the patient's quality of life, since the ulcers are painful, difficult to heal and often prolong hospitalization periods. Despite considerable attempts to prevent pressure ulcers, prevalence figures remain unacceptably high. In a prevalence study involving more than 16,000 patients in the Netherlands, a mean prevalence of 23.1% in health care institutions was reported [6]. Pressure ulcers are often classified in four different stages, ranging from discoloration of intact skin (Stage I) to full thickness skin loss involving tissue damage that extends to underlying bone involving both fat and muscle tissues (Stage IV). Although this classification is widely used in clinical practice, it does not necessarily relate to the origin of the ulcers. Depending on the nature of loading, pressure ulcers can either initiate superficially at the skin [15][33], or initiate in deeper layers such as muscle tissue [14][18][20][28]. The present study focuses on deep pressure ulcers that initiate in muscle tissue, since deeper ulcers are more harmful and show more extensive ulceration. In addition, muscle tissue is more susceptible to the development of pressure ulcers [2][23] and, hence, deep ulcers develop at a faster rate than superficial ulcers, making them particularly dangerous [2][14]. Yet, these deep ulcers are difficult to prevent and identify, since they are rarely visible at the skin surface at the time of initiation. As such, the four stage classification scheme can be misleading, since it does not represent an ordinal scale. In literature, a number of theories have been proposed to explain the pathophysiology of pressure ulcers. These theories suggest that compression of a tissue can lead to localized ischaemia, impaired interstitial fluid flow and/or insufficient lymphatic drainage. Furthermore, relieving the tissue after sustained compression may lead to reperfusion injury. Recently, it was demonstrated that the deformation of cells due to external loading of the tissue can directly induce cell damage [8]. The primary cause of deep pressure ulcers is the external load applied at the patient support interface, resulting in compression of the tissue between the skin surface and the bony prominences. However, the externally applied load is not indicative of the local mechanical conditions in underlying muscle tissue (for example expressed in terms of stresses and strains), and thus not directly related to tissue damage [12][24][30]. In particular, when a tissue is compressed against an irregularly shaped bony prominence, the local mechanical condition within the muscle tissue may well exceed the measured loading condition at the skin interface. Therefore, the local mechanical loading condition could prove a more reliable predictor for the onset of tissue damage in these deeper tissue layers. When considering the local mechanical tissue condition, it should be noticed that an averaged mechanical condition associated with a small volume within the tissue, is not representative of the mechanical condition experienced at the cellular level. This is due to the heterogeneity of the microstructure [10][17][31]. Since tissue damage initiates with local cellular damage [7][11][20][23], it is necessary to consider this microstructure. In addition, the microstructural behavior must be considered since it inevitably determines the macroscopic constitutive behavior of the tissue. For example, when cell damage occurs, the microstructure is likely to change, which will be reflected in the macroscopic behavior of the tissue. In this case, it is not possible to describe the macroscopic behavior with a conventional constitutive law [10][21]. Since local mechanical conditions are difficult to measure experimentally, theoretical and numerical models have been developed, which relate externally applied pressures to the local mechanical condition within a tissue. In a theoretical model based on dimensional analyses, Sacks [27] derived a relationship between tolerable external pressure and duration of pressure. The rationale behind this analysis was that there is a definable pressure that causes a pressure ulcer, which is a function of both tissue properties and the blood flow through the tissue. The model did not take into account the local geometry of, for example, a bony prominence, leading to load distributions in the tissues. Zhang and coworkers [33] performed a theoretical analysis on the stress distribution within the tissue after application of shear and normal forces at the skin. To allow calculation of an analytical solution, both skin and muscle tissue were assumed to behave as linear, isotropic elastic materials. This model demonstrated that the highest stress concentrations were found within deeper layers of the soft tissue. To analyze more complex geometries and material behavior, the use of computer models, in particular the finite-element (FE) approach, is indispensable. Chow and Odell [12] and Todd and Tacker [30] developed finite element models of the human buttocks. In the model of Todd and Tacker [30], seated positions were simulated, thereby manipulating boundary conditions of the model. The authors concluded that there is no clear correlation between interface pressure and the local mechanical conditions. Oomens and coworkers [24] created a FE model of a human subject sitting on a cushion, which incorporated three different tissue layers overlaying the human ischial tuberositas, muscle, fat and skin. These soft tissues were modeled as nonlinear viscoelastic materials. Despite the uncertainties in material properties, the high peak stresses were consistently found near the bone prominences and in the fat layer. Furthermore, models based on mixture theory have been proposed to examine the transient biomechanical response of a skin layer as a result of tissue fluid flow within the tissue [22][33]. The numerical models described in literature focus on determination of local mechanical conditions in skin and underlying tissues in terms of homogenized tissue stresses and strains [12][22][25][30][32][33]. However, from the previous discussion it is clear that a microstructural analysis is required to determine the mechanical conditions that a cell experiences. Moreover, knowledge of the local mechanical condition alone is not sufficient to predict tissue damage initiation and evolution. Also the loading history of the tissue is essential, since the time that a tissue is subjected to a sustained compression is a major determinant of tissue damage [26]. A second aspect that, to date, has received relatively little attention, is the tissue tolerance against compression. Different tissues, such as skin, fat and muscle, may have a different tolerance level, which in turn may be patient dependent. The objective of the present study is to illustrate that prediction of pressure ulcer initiation on the basis of external load measurements is inadequate. By considering local load-time threshold curves, it is illustrated which variables quantitatively influence the threshold curves and, therefore, should be considered for the prediction of damage initiation. To this end, a numerical model was developed, which is based on a multilevel FE approach. This model can relate external loads applied to the skin, to the local mechanical conditions at the cell level. With this model, simulations were performed in which muscle tissue is compressed against a bony prominence. As a starting point, the model focuses on the role of cell deformations on cell damage. The model incorporates both the time aspect and a tissue tolerance level for damage in the form of a damage law that was derived from in vitro experiments [9]. A parameter study was performed to illustrate the effect of the cell tolerance and cell stiffness on the macroscopic tissue damage evolution.