Characterizing Hypoxia, Neutrophil Persistence and Revascularization in the Murine db/db Model of Type II Diabetic Impaired Skin Healing
Abstract
Impaired skin healing represents a significant clinical burden. In the diabetic, inflammatory aberrations, hypoxia and insufficient angiogenesis all result in negative wound healing outcomes - repeated infections, poor perfusion and ultimately amputation. Previous research has reported comparable levels of neutrophils in closed wounds up to 4-12 weeks old. Our study interest was in investigating the dynamics of hypoxia resolution, neutrophil persistence and angiogenic response in the db/db model. Contrary to our hypothesis, we observed significantly higher hypoxic load in the wild types at days 3 and 7. Additionally, we observed significantly elevated neutrophil numbers at day 7 db/db wound bed and an angiogenic deficit at day 3, with wild types exhibiting significantly more CD31+ cells. Our results validate the db/db model as one of impaired healing, and are consistent with literature in the field suggesting a potential deficit in hypoxic adaptation resulting in an overall delayed wound healing process.