Flexible Electrical Stimulation Device With Chitosan-Vaseline Dressing Accelerates Wound Healing In Diabetes

Background:Endogenous electric fields(EFs)generated after skin damage can sitimulate cells migrate to the center of wounds,which plays an important role in the wound healing process.But,the endogenous EFs of diabetic wounds tend to be exhausted.Additionally,applied electrical stimulation(ES)has been proved to be therapeutic for diabetic wounds by stimulating the endogenous EFs.However,the numerous inconsistencies in the published literature have led to conflicting results and substantial uncertainties with respect to electrical parameters,such as the type of electric current and its voltage.And the mechanism of ES to promote wound healing in diabetes has not been studied in depth.Moreover,ES device currently used in clinics are large and inconvenient for patients to apply.In addition,chitosan has exciting effects of antibacterial,moisturizing and immune regulation,providing a good external microenvironment for wound healing.Our previous research found that the Chitosan-Vaseline gauze(CVG)made of the chitosan mixture and Vaseline,compared to Vaseline gauze,can promote wound healing better.But the effects of combined ES and CVG have not been studied yet.Thus,for the convenience of patients and the overall curative effect,we planned to manufacture a portable and effective dressing that combined the advantages of ES and CVG in this study.Objective:To initially select ES parameters that promote wound healing in type 2 diabetes mellitus(T2DM)rats,and to explore the possible mechanism of ES in vitro;To evaluated the effect of the flexible ES Chitosan-Vaseline dressing on the wound healing in T2DM rats,according to the optimized results of ES parameters in vivo,and combined with CVG.Methods:(1)First,Sprague-Dawley(SD)rats were used to establish a model of T2DM.Then wound healing experiments were performed in order to optimize the ES parameters by collecting the statistics of the gross photos of the healing process,and the possible mechanism of ES was initially explored.(2)In vivo,in order to reproduce conditions similar to those associated with T2DM patients,we examined the apoptosis,proliferation and migration capacity of HUVECs in high D-glucose and high palmitic microenvironment.And we explored the possible effects and mechanisms of ES on HUVECs by using EdU cell proliferation assay,wound healing assay and Transwell assay.(3)Based on aforementioned optimized results,we manufactured a rigid circuit board of the ES device.After testing the performance,a flexible ES device was manufactured that included the same functional elements.CVG was then added to make the flexible ES Chitosan-Vaseline dressing.Finally,we evaluated the effects and the underlying molecular mechanisms of the dressing to promote wound healing by using photographs of wound healing process,histopathological examination and western blotting.Results:(1)Compared to other groups,High Voltage Monophasic Pulsed Current(HVMPC)was the better ES parameter to promote wound healing in T2DM rats.(2)25 mM D-glucose combined with 0.2 mM palmitate could significantly induce cell apoptosis and inhibit cell proliferation and migration;ES could up-regulate the expression of p-Akt and p-ERK1/2 of HUVECs.HVMPC could promote cell proliferation and migration,and the effect was blunted in cultures treated with either their inhibitor LY294002 or U0126.(3)Flexible ES Chitosan-Vaseline dressing accelerated the wound healing rate in T2DM rats and shorten the healing time;the dressing promoted blood vessel formation and up-regulated the expression of VEGF,p-Akt and p-ERK1/2;the dressing accelerated wound epithelialization and improved the quality of wound healing.Conclusion:We found that HVMPC combined with CVG was possible to promote the healing of diabetic wounds by accelerating angiogenesis and enhancing reepithelialization.In addition,the dressing could improve the quality of wound healing and reduce the formation of scar tissue.