Abstract
Nitric oxide (NO) is a critical molecular signal and mediator for normal wound healing. Nitric oxide deficiency has been established as an important mechanism responsible for poor healing in diabetic foot ulcer (DFU) patients. Preliminary clinical wound healing studies using wound fluid nitrate determinations, as measures of wound NO bioactivity, suggest that threshold wound fluid nitrate values may function as an effective diagnostic indicator of successful wound healing for the DFU patient. In this case, wound fluid nitrate measurements could predict the suitability of a wound for specialized wound therapies such as topical growth factors or bioengineered skin substitutes. Wound fluid nitrate determination would also identify DFU patients with wound NO deficiency-related impaired healing that may promote wound complications possibly leading to lower-extremity amputation. With clinical validation, wound fluid nitrate may qualify as a wound healing biomarker and surrogate endpoint for DFU treatment. Additionally, combined diagnostic determinations of wound NO bioactivity, bacterial load, and matrix metalloproteinase production will enhance DFU management by providing quantitative parameters for clinical wound treatment. The impact of wound fluid nitrate determination and the combined platform of wound diagnostic indicators for wound healing prediction and clinical treatment, respectively, is anticipated to provide substantial costs savings and improved outcomes for the DFU patient.