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 60 kPa at the skin surface leads to a decrease in oxygen partial pressure from a physiological value of 65 mmHg to a hypoxic level of 31 mmHg. 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.