Venous ulcers are the most common and severe skin wounds occurring in lower legs. They are painful, hard to heal and have a 78% chance of recurrence after two years, which leads to frequent visits to wound care clinics and results in huge financial burdens to the patients, family, and society. Contemporary treatments include compression stockings, drugs, and surgeries. However, these only treat the ulcers after they have occurred. Therefore, it is necessary to understand the pathology of ulcer formation, which will then allow us to predict the onset of an ulcer and implement preventive measures early.

The commonly accepted theory of venous ulcer pathology is that the ulcers are caused by chronic venous insufficiency (CVI) which is a resultant of calf muscle pump failure. CVI causes blood pooling in the lower leg, leads to inflammation, skin edema, tissue necrosis, and ultimately skin ulcers. However, various hypotheses existed between the stages of blood pooling and the ulceration.

Therefore, the goals of this research were to:​ i) determine the blood flow response to loading in lower legs between venous ulcers patients and a healthy population;​ ii) quantify the hemodynamic parameters that contribute to the differences in blood flow;​ iii) understand the progressive changes between inflammation and skin edema in the development of skin ulcers.

To address the first goal, a blood perfusion test was performed on the lower legs of ulcer patients and a healthy group. External normal, and combined normal and shear loads were applied to the lower legs. The blood perfusion profiles were analyzed and results showed that the ulcerated legs were significantly different than healthy legs in response to load and reactive hyperemia. The legs that did not have open wounds but were from the same ulcer patient exhibited an intermediate trend between the wounded and healthy legs. This suggests a progressive change existed during ulcer development.

The second goal was achieved by the development of a Windkessel based circuit model. The model output was compared with the blood flow profiles from the perfusion tests. Patient-specific parameters were obtained and compared across the wounded, non-wounded, and healthy legs. Results indicated that significant differences existed in localized vessel resistance and compliance between wounded and healthy legs, suggesting a threshold of those parameters existed from each category. The results explained the differences in locally measured blood perfusion and indicated the potential of identifying populations at risk of developing venous ulcers.

Finally, the third goal was reached by the development of a skin Finite Element (FE) model with series of parametric studies. The influence of the glycosaminoglycans (GAGs) and sodium during inflammation on the skin edema and tissue damage were explored. Results showed that the increased GAGs and sodium content led to edema and an increased fluid pressure within the tissue. This explained the increased reactive hyperemia from wounded legs in the perfusion tests. Increased fluid pressure causes tissue ischemia and an increased tissue stress;​ both have been shown to cause tissue damage and wound formation. The FE model provides insights to the detailed pathological events that happen between inflammation, edema and skin ulceration.