Deep tissue injury due to prolonged excessive skin loadings can lead to clinical pressure ulcers, affecting millions of persons with physical disability. How skin loadings are transmitted to deep tissues, and how stresses at the tissue level invoke cellular damages require objective-specific in-silico simulations, as well as careful in-vivo and in-vitro studies. Our findings suggest interesting implications of damage vulnerability at the cellular level under prolonged oxidative exposure during chronic inflammation at the tissue level, and the potential benefit of intermittent vibration and poloxmamer-188 to the risk management of deep tissue pressure ulcers.