Abstract
Diabetic foot ulcers (DFUs) pose a significant challenge in wound care due to their chronic nature and impaired healing processes. This study examines the biogenic amines and small molecule metabolites present in DFU wound exudates to identify their potential roles in wound healing. Under an IRB-approved protocol, wound fluid samples were collected from 25 diabetic patients and analyzed using ultrahigh-pressure liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The analysis identified 721 metabolites, with 402 confirmed through stringent criteria. Key metabolites significantly contributing to the wound exudates include betaine, lactic acid, carnitine, choline, creatine, and metformin (a widely used first-line treatment for type 2 diabetes). These molecules are known to influence wound healing processes, such as collagen synthesis, angiogenesis, inflammation modulation, and energy metabolism. Notably, the presence of drugs such as metformin and beclomethasone in the exudates suggests significant pharmacodynamic interactions that could influence wound healing. Specifically, we discovered that the combined use of insulin and metformin administered systemically significantly increased the concentration of metformin in the wound exudates (from 0.3% ± 0.0 to 3.1% ± 3.4; p = 0.00 49). This study highlights the complexity of DFU exudate composition and underscores the potential for targeted metabolic profiling to develop personalized wound care strategies.