Collaborative Research: An in vivo/in silico Approach to Delineate the Effect of Age on Pressure Ulcer Susceptibility

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Pressure ulcers, or bed sores, are a debilitating condition that affects more than 3 million Americans. Today, it is understood that pressure ulcers follow from continued compression of skin in patients that have lost the ability to reposition themselves and relieve that pressure. For example, patients in wheel chairs or patients that have become bedridden frequently suffer from pressure ulcers. Patients of advanced age are particularly prone to pressure ulcers. While we understand the behavioral factors that may, in part, explain this increased incidence, the age-related anatomical and physiological factors that may contribute to increased risk in patients of advanced age have remained mostly unexplored and unknown. This knowledge is important, as it may provide a pathway to age-specific treatment strategies. This project will use a mouse model of pressure ulcer formation and progression to investigate these age-related anatomical and physiological factors and their contribution to the increased risk of pressure ulcers due to age. Furthermore, the research will integrate these results into a comprehensive computational model that will be a first step toward predicting pressure ulcers. With such a model it will be possible to not only design better support systems -- such as wheelchairs, mattresses, and prostheses -- but also to explore novel diagnostic technologies and therapeutic strategies. This project will integrate a diverse group of undergraduate students into the research, using peer mentoring approaches. Finally, and most importantly, in order to accelerate the transfer of knowledge from this study to the general public, educational podcasts on pressure ulcers will be designed that will be disseminated by integrating them into successful, long-running podcast series.The overall goal of this research is to quantify the effect of age on non-behavioral factors of pressure ulcer formation using mice as a biological model system in combination with a novel multi-scale, multi-physics computer model. This goal is supported by two objectives. The first will determine the non-behavior factors that increase the risk of pressure ulcer initiation in the elderly. Using young and old mice, the role of skin compliance in the microvascular collapse and ischemia that occurs prior to pressure ulcer will be investigated. The second objective is to determine the non-behavioral factors that increase the risk of pressure ulcer progression by looking at three contributory factors: ischemic injury, reperfusion injury, and mechanical injury. For both objectives, the experimental data will be integrated into a multi-scale, multi-physics model that will then be able to link matrix-cell and cell-cell signalling to pressure ulcer formation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.