Chapters authored
Macrophages as a Target for Treating Diabetic Foot Ulcers
In all stages of wound healing, macrophages play a pivotal role by coordinating the repair steps in a timely and accurate fashion. The successful completion of wound healing requires proper spatiotemporal presence and function of macrophages. Diabetes significantly alters the proliferation, polarization and functionality of macrophages, leading to a suboptimal but prolonged pro-inflammatory M1-like phenotype in wound macrophages and a failure of their late transition to a reparative M2-like phenotype. This defect in macrophage phenotype and the proper transition results in delayed or even failure of wound healing. Specifically in the diabetic foot ulcer (DFUs), this macrophage dysfunction results in chronic infection and potentially amputation. The abnormal macrophage phenotype in diabetes is not fully understood but is believed to mainly result from epigenetic changes in macrophages and altered interactions between macrophages and other cell types, such as fibroblasts, endothelial cells, neutrophils and T-cells. Recent research on DFUs has focused on developing strategies to improve diabetic wound repair through modulation of macrophage polarization. Treatment of DFUs will greatly benefit from a multi-modal therapy that includes controlling high blood glucose, topical support, prevention of secondary infection, resolution of sustained inflammation and application of cellular therapies targeting macrophages.
Part of the book: Diabetic Foot