Clinical Efficacy Assessment of Potential Biological Indicators Present in Diabetic Foot Ulcers (DFUs) Exudates in Predicting Wound Healing Progress: A Systematic Review

Introduction: The aim of this research was to detect potential biological indicators that have been documented in the wound exudate of diabetic foot and assess their capacity to accurately manifest the present and forthcoming process of healing in diabetic foot.Method: A systematic inquiry was conducted in accordance with the PRISMA methodology across three designated databases: Scopus, Embase and MEDLINE. Employing carefully selected keywords and expressions, the search produced a total of ۳۲۵۴ outcomes.Results: After applying predefined inclusion and exclusion criteria, a comprehensive analysis was conducted using a total of ۱۷ selected papers. Out of these, five papers provided insights into the sequential temporal changes of biological indicators within wounds. Additionally, six papers investigated the baseline measures and their association with the rate of healing and/or final outcome of healing. Four papers presented data on both endpoints, while two papers specifically concentrated on the baseline levels of biological indicators in a generalized cohort of individuals with diabetic foot ulcers.In the collective analysis of these papers, a total of ۳۵ distinct biological indicators were detected in the diabetic foot exudate of ۹۰۰ patients. These biological indicators encompassed a range of categories, such as cytokines, growth factors, proteases, chemokines and protease inhibitors. It is worth noting that proteases represented the largest subgroup, accounting for ۱۶ markers (۳۴.۸%) of the investigated biological indicators across seven studies. Among the proteases, matrix metalloproteinase-۹ (MMP-۹) stood out as the most extensively studied enzyme, demonstrating significant potential as a biomarker in five of the studies.Conclusion: The association between wound bacterial profiles and the outcome of wound healing showed variations across the five studies that examined this aspect. Furthermore, one study focused on biophysical markers, such as measuring the pH of wound exudate, instead of traditional biological indicators. In general, the quality of the studies included in the analysis was deemed to be high. However, conducting quantitative comparisons between the papers proved challenging because of the variations in experimental setup, including differences in sampling methods and evaluation techniques.