A Computational, Tissue-Realistic Model of Pressure Ulcer Formation in Individuals with Spinal Cord Injury
Fig 5
Sensitivity analysis reveals a unique contribution for all damage mechanisms, but simulated tissue is most sensitive to oxygen.
(A) We partitioned parameter values according to which damage mechanism they affected. Panel (B) shows a global sensitivity analysis comparing the effects of the three mechanisms of damage on tissue health outcomes. Each mechanisms is simulated at two levels: with maximal or negligible effects. In panels C-E, sensitivity analysis was performed on parameters within each mechanistic module. All sensitivity analyses are shown with model snapshots at time t = 400 h (approximately 2.5 weeks). Default parameters are marked with asterisks. (C) Tissue sensitivity to oxygen parameters. The parameter governing oxygen production varies in each row. Each column represents a value of the parameter controlling how sensitive the tissue is to local oxygen concentrations. When oxygen production is plentiful, the simulated tissue becomes insensitive to other oxygen parameters (bottom row). Panel (D) illustrates tissue sensitivity to pressure intensity and period. Pressure intensity varies in each row. Each column represents a value of pressure cycle length. As the cycle length increases, the number of reperfusion events decreases for the same period of ischemia. Increased pressure leads to more damage, while fewer reperfusion events lead to lower damage at t = 400 h. Panel (E) illustrates tissue sensitivity to inflammatory mediators. Each column represents a value of the parameter controlling how sensitive the tissue is to local TNF-α concentrations. The parameter controlling tissue sensitivity to TGF-β1 varies in each row. Increasing sensitivity to TNF-α leads to earlier ulceration and more damage, while increased sensitivity to TGF-β1 leads to decreased tissue damage.