Comparative Efficacy of Regenerative Therapies for Diabetic Foot Ulcers

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most dreaded complications of diabetes mellitus and is associated with a high risk of lower limb amputation and mortality. Because the efficacy of conventional treatments for DFUs is often limited, regenerative medicine therapy, such as growth factors and stem cells, may provide a solution to chronic wound healing. In this study, we compared several kinds of regenerative therapy for treating DFUs in terms of efficacy. METHODS: We systemically searched relevant studies on PubMed, Cochrane Library, and EMBASE. Randomized clinical trials on conventional treatment combined with platelet-rich plasma (PRP), epidermal growth factor (EGF), or stem cell therapy, compared with conventional treatment alone in patients with DFUs, were included in this study. RESULTS: A total of 1454 patients from 23 randomized controlled trials (RCTs) were included in the network meta-analysis. In terms of the number of completely healed ulcers, no significant difference was noted between PRP, stem cell therapy, and EGF group. We also performed surface under the cumulative ranking curve analyses to predict the rank of each intervention by the number of completely healed ulcers. The predicted ranking was as follows: stem cell, PRP, EGF, and the control group (conventional treatment alone). Furthermore, when we compared the mean of the wound healing time of DFUs among these four interventions, we found that the PRP group achieved significantly earlier ulcer healing than the stem cell, EGF, and control groups. No significant difference was observed in the time needed for wound healing between the stem cell and EGF groups. Funnel plot analysis demonstrated no publication bias. CONCLUSIONS: PRP combined with conventional treatment significantly accelerates wound healing for DFUs. The mean wound healing time was similar between the stem cell and EGF groups. However, additional reviews of rigorous, large, well-designed RCTs are warranted for further validation of our findings.