Non-invasive Pulsed Electric Field Dressing Promotes Refractory Wound Healing And Mechanism Study

Objective: To develop a new non-invasive pulsed electric field(PEF)dressing and apply it on the back wound of type 2 diabetes mellitus(T2DM)rats for the characterization of wound healing and to investigate the mechanism.METHODS: A non-invasive PEF dressing was prepared by integrating forked finger electrode into the dressing and outputting a pulsed electric field from a function generator.The new dressing was applied to the wounds of T2 DM rats and divided into strong pulsed voltage group,weak pulsed voltage group and blank control group and the wound healing rate was calculated.Histological staining of skin specimens was performed to observe the healing status of tissues in the wounds;the expression levels of epidermal growth factor,vascular endothelial growth factor and platelet-endothelial cell adhesion molecules in the wounds were measured by tissue immunological assay technique.Changes in dissociin-metalloproteinase 17 and differentiation cluster antigen9 expression at the cellular level in the PEF environment were detected by cellular protein immunoblotting techniques.Image J Pro1.5.1 software(National Institutes of Health,USA)and Graph Pad Prism 9.0 software(Graph Pad Software Inc,USA)were used for quantitative analysis and statistical tests of the results.RESULTS: The non-invasive PEF dressing could be safely applied to the rat dorsal wounds,and the electrodes were not directly applied to the wounds or skin,thus avoiding the electrochemical side effects of electrode materials.Characterization experiments demonstrated that the healing rate of the IPV group was better than that of the WPV group,while the WPV group was better than the BC group(P < 0.05);there was a similar trend in the expression of EGF,VEFG,and CD31 in the traumatic tissue between the groups.In the PEF in vitro cell stimulation assay ADAM17 expression was higher in the IPV group than in the WPV group,and higher in the WPV group than in the BC group(P < 0.05);in contrast,the expression trend of CD9 was opposite to that of ADAM17 among the groups(P < 0.05).CONCLUSIONS: Non-invasive PEF dressings were shown to accelerate wound healing in T2 DM rats,and PEF may mediate the pro-epidermal repair effect through the ADAM17/EGF/EGFR signaling axis and regulate the migration phenotype of keratinocytes by affecting the level of CD9 expression within the wound to achieve rapid wound closure.In addition,PEF may upregulate VEGF expression in traumatic tissues,mediating angiogenesis through Vascular Endothelial Growth Factor Receptor(VEGFR)and improving the angiogenesis barrier in T2 DM wounds to accelerate wound healing.