Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Anatomy and Cell Biology

Supervisor

Hamilton, Douglas W.

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.

Summary for Lay Audience

Type II Diabetes is a disease that arises from the body’s inability to deliver sugar into cells effectively. The result is increased levels of sugar in the blood, often for a very prolonged period of time. Diabetics are also at increased risk for wounds, especially on their feet due to issues with their blood vessels and nerves, which result in poor sensation. Once a wound is created, it often starts a cycle of trauma, inflammation and repeated infection. Diabetics are at a greatly increased risk for foot amputation, and the prognoses following these operations is often poor.

Hypoxia, inflammation and new blood vessel formation are all well-known factors in wound healing. The purpose of this work is to utilize a diabetic and healthy mouse model, to attempt to outline any differences between them with respect to these parameters. The use of such models allows researchers to model complex pathologies in a relatively quick and inexpensive manner. We seek to uncover differences between healthy and diabetic mice in order to further our understanding of what is different between how a diabetic and a healthy person and potentially extrapolate these findings to the discovery of new therapeutics.

Hypoxia, inflammation and vascular are all attractive and promising areas of research for the development of new therapeutics. In the present study we aimed to outline differences in how quickly hypoxia resolves, and whether we could establish a relationship between its resolution, the amount of inflammation present in the tissue and the amount of new blood vessel ingrowth into the wound.

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