Comparative efficacy of advanced therapeutic modalities for diabetic foot ulcers: a systematic review and meta-analysis including NPWT, stem cells, ESWT, and bioengineered treatments

Background Diabetic foot ulcers (DFUs) are highly debilitating and often necessitate cutting-edge treatments apart from the usual care. This systematic review and meta-analysis have compared the efficacy of Negative Pressure Wound Therapy (NPWT)/VAC, cell-based therapies (MSC-based therapies), artificial skin, extracorporeal shockwave therapy (ESWT), and platelet-rich plasma (PRP) interventions in promoting healing of difficult wounds, as well as healing by other means. Methods The extensive search identified 49 randomized controlled trials. For data analysis, a random-effects model with inverse-variance weighting was used to obtain standardized mean differences (SMDs) with 95% confidence intervals (CIs). The presence of publication bias was determined using funnel plots and Egger’s test, while the quality of the studies was assessed by means of Jadad scores and risk of bias tools. GRADE was employed to assess the certainty of the evidence. Results Sub-group analysis revealed that NPWT significantly accelerated wound closure compared to standard care SMD of −0.39 (95% CI: 0.57 to −0.21; I 2 = 49%), indicating faster healing times, used days to measure time showed an SMD of −0.94 (95% CI: 1.07 to −0.80; I 2 = 0%) which showed that patients healed at a faster rate. The comparison of different devices and techniques showed an SMD of 0.98 (95% CI: 0.75–1.21; I 2 = 0%), indicating that additional treatments resulted in a greater reduction in wound area. The results were statistically significant because all p-values were lower than 0.05. MSC-based therapies showed similar overall healing (SMD = 0.46, 95% CI: 0.24–0.69) and faster closure (SMD = −1.04, 95% CI: 1.28 to −0.8). Additionally, trials of bioengineered skin substitutes, ESWT, and PRP all showed statistically significant improvements in time to wound closure and overall healing. Relative to the control group, adverse events were fewer in the NPWT and PRP groups (SMD = −0.24, 95% CI: 0.42 to −0.05). Conclusion The NPWT and MSC-based therapy, in particular, represent major improvements in healing outcomes for diabetic foot ulcers (DFUs) and in the speed of closure compared with standard treatment.