Research progress on and molecular mechanism of vacuum sealing drainage in the treatment of diabetic foot ulcers

Abstract

Diabetic foot ulcers (DFUs) are common chronic wounds and a common complication of diabetes. The foot is the main site of diabetic ulcers, which involve small and medium-sized arteries, peripheral nerves, and microcirculation, among others. DFUs are prone to coinfections and affect many diabetic patients. In recent years, interdisciplinary research combining medicine and material science has been increasing and has achieved significant clinical therapeutic effects, and the application of vacuum sealing drainage (VSD) in the treatment of DFUs is a typical representative of this progress, but the mechanism of action remains unclear. In this review, we integrated bioinformatics and literature and found that ferroptosis is an important signaling pathway through which VSD promotes the healing of DFUs and that System Xc-GSH-GPX4 and NAD(P)H-CoQ10-FSP1 are important axes in this signaling pathway, and we speculate that VSD is most likely to inhibit ferroptosis to promote DFU healing through the above axes. In addition, we found that some classical pathways, such as the TNF, NF-κB, and Wnt/β-catenin pathways, are also involved in the VSD-mediated promotion of DFU healing. We also compiled and reviewed the progress from clinical studies on VSD, and this information provides a reference for the study of VSD in the treatment of DFUs.

Keywords: clinical treatment; diabetic foot ulcers; molecular mechanism; trauma repair; vacuum sealing drainage.

Figure 1

KEGG pathway analysis. (A) The bar graph shows the summarized significant signaling pathways ranked by the number of genes present in each signaling pathway. (B) Significant KEGG pathway enrichment of DEGs. The pathways are ranked by the number of enriched genes. (C) Mesh diagram showing common gene intersections occurring in meaningful signaling pathways. DEGs, differentially expressed genes; KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 2

Ferroptosis signaling pathway and photographs of the clinical treatments. (A) Ferroptosis is an effective signaling pathway by which VSD can treat DFUs. Genes labeled in green show decreased expression after VSD treatment of DFUs and generally promote iron death; genes labeled in red exhibit increased expression after VSD treatment of DFUs and generally inhibit iron death. The three genes in the purple frame comprise the first iron-death pathway (System Xc-GSH-GPX4), and the three genes in the blue frame form the second iron-death pathway (NAD(P)H-CoQ10-FSP1). The two large frames in brown indicate the conversion of Fe²⁺ to Fe³⁺, and the two large frames in yellow indicate the conversion of Fe³⁺ to Fe²⁺. (B) Photographs of DFUs treated with VSD.