Macrophage polarization and diabetic wound healing

Diabetes mellitus is a costly disease and nearly one-third of these costs are attributed to management of diabetic foot disease including chronic, non-healing, diabetic foot ulcers. Therefore, much effort has been placed into understanding the pathogenesis of diabetic wounds and novel therapeutics. A relatively new area of interest has been macrophage polarization and its role in diabetic wound healing. Diabetic wounds show dysregulated and persistent M1 (pro-inflammatory) macrophage polarization whereas normal wounds will display a transition to M2 (pro-healing) macrophages around day three after wounding. We reviewed factors known to affect macrophage polarization, mostly focused on those that contribute to M2 macrophage polarization, and potential treatments that at least in part target macrophage polarization in the diabetic wound bed. Much of the work has been aimed at reducing hyperglycemia and encouraging pro-inflammatory cytokine neutralization or decreased expression given this has a significant role in producing M1 macrophages. Treatment of diabetic wounds will likely require a multi-modal approach including management of underlying diabetes and control of hyperglycemia, topical therapeutics, and prevention of secondary infection and inflammation. (Translational Research 2021; 236:109-116)