Deferoxamine can prevent pressure ulcers and accelerate healing in aged mice

Abstract

Chronic wounds are a significant medical and economic problem worldwide. Individuals over the age of 65 are particularly vulnerable to pressure ulcers and impaired wound healing. With this demographic growing rapidly, there is a need for effective treatments. We have previously demonstrated that defective hypoxia signaling through destabilization of the master hypoxia-inducible factor 1α (HIF-1α) underlies impairments in both aging and diabetic wound healing. To stabilize HIF-1α, we developed a transdermal delivery system of the Food and Drug Administration-approved small molecule deferoxamine (DFO) and found that transdermal DFO could both prevent and treat ulcers in diabetic mice. Here, we demonstrate that transdermal DFO can similarly prevent pressure ulcers and normalize aged wound healing. Enhanced wound healing by DFO is brought about by stabilization of HIF-1α and improvements in neovascularization. Transdermal DFO can be rapidly translated into the clinic and may represent a new approach to prevent and treat pressure ulcers in aged patients.

Wound healing: cellular mechanisms and pathological outcomes

“…[ 117 ] suggest that iron deposition caused delayed healing in diabetic foot ulcers, promoting an unrestrained M1-like macrophage phenotype, increased oxidative stress and senescence. Similarly, others have shown that the iron chelator, deferoxamine, improves wound healing in pressure ulcers of diabetic [ 147 ] and aged [ 148 ] mice. Thus, the cellular effects of iron are probably context-dependent and wound-type-specific, exacerbating tissue damage in an already pro-inflammatory environment, while promoting alternatively activated macrophage- and fibroblast-mediated wound resolution in late-stage repair.…”

A comparative analysis of deferoxamine treatment modalities for dermal radiation‐induced fibrosis

“…DFO has promise as a safe, effective treatment with the potential to fill this void, but uncertainty remains regarding the best delivery route. Recently, topical administration of DFO has been studied in wound‐healing experiments 22‐25 22 .…”

Stimuli‐Responsive Delivery of Growth Factors for Tissue Engineering

“…[ 9–15 ] As reported in previous studies, tissue injuries lead to site‐dependent environmental changes and abnormal cellular activity. Multiple factors, including enzymes, [ 16–36 ] reduction and oxidation (redox) reactions, [ 37–44 ] hypoxia, [ 32,45–49 ] pH, [ 47,50–54 ] temperature, [ 55–57 ] and the other characteristics, [ 42,58–60 ] become dysregulated at the onset of injury or during the progression of the healing ( Figure A). These hallmarks can be monitored to serve as a reference to evaluate the extent of injury, stage of wound healing, and necessity for treatment.…”