A HIERARCHICAL APPROACH TO STUDY DAMAGE EVOLUTION IN SKELETAL MUSCLE - A CONTRIBUTION TO PRESSURE ULCER RESEARCH

Pressure ulcers are localized areas of tissue breakdown in skin and/or underlying tissues. They result from prolonged mechanical loading, typically common in subjects who are bedridden, wheelchair bound or wear a prosthesis. The sores are painful, difficult to treat and represent a burden to the community in terms of health care and money. Prevalence figures remain unacceptably high, ranging between 8 % and 23 %. The costs associated with the management of pressure ulcers in the U.S. exceed $ 6.4 billion annually [1]. The high prevalence figures can partly be attributed to a limited understanding on how and why pressure ulcers develop. Although a lot is known about risk factors and prevention and treatment strategies a clear view on the basic pathways, whereby mechanical loading leads to soft tissue breakdown is still missing. Several hypotheses can be found in the literature on the causes of pressure sores. Local ischemia due to occlusion of blood vessels is generally accepted as a major risk factor. Several other risk factors have been implicated including reperfusion injury [2], impaired interstitial fluid flow [3], lymphatic drainage [4] and sustained deformation of cells [5]. What is certain is that in order to reduce the prevalence of pressure ulcers, it is essential to improve and expand the knowledge of the etiology in terms of basic science and clinical practice. For this purpose, we have adopted a hierarchical approach, studying the effects of loading in distinct, yet complementary model systems with increasing length scales and complexity. This implies studies at the level of individual cells in culture, studies on model systems of tissue engineered biological tissues, animal studies and human studies. Experimental studies should aim at elucidating the relationships between mechanical loading, the pathophysiological response and tissue breakdown in testing hypotheses on the etiology. Computer models are used to predict the association between external and internal mechanical conditions and to assess the validity of extrapolating between different hierarchical model systems. The objective of the present study is to show how such an approach study might work. In particular, can results from the loading of tissue engineered constructs be used to predict the outcome of animal experiments? Bosboom et al. [6,7] performed experiments, in which the tibialis anterior of anaesthetised rats was loaded for 2 hours with an external indentor at a pressure 250 kPa. After 2 hours the load was removed and the rats were allowed to recover from anaesthesia. After 24 hours the location and amount of tissue damage in the muscle were determined with a combination of T2weighted Magnetic Resonance Imaging (Fig.1 ) and histological techniques.