Conductive polyphenol microneedles coupled with electroacupuncture to accelerate wound healing and alleviate depressive-like behaviors in diabetes

Abstract

Inflammation and depression are serious complications of diabetes that interact to form a feedback loop and may hinder diabetic wound healing. They share a common pathophysiological basis of abnormal interactions between diabetic wounds and the brain. Here, we propose a strategy combining electroacupuncture (EA) stimulation of the Dazhui acupoint (GV14) with polyphenol-mediated conductive hydrogel microneedles to promote diabetic wound healing and alleviate depression through local wound–brain interactions. The conductive microneedles comprised methacrylated gelatin, dopamine (DA), DA-modified poly(3,4-ethylenedioxythiophene), and Lycium barbarum polysaccharide. EA at GV14 activated the vagus–adrenal axis to inhibit systemic inflammation while DA coupled electrical signals for long-term inhibition of local wound inflammation. EA at GV14 was also found to elevate 5-hydroxytryptamine levels in rats with diabetic wounds, consequently mitigating depressive-like behaviors. Additionally, the polyphenol-mediated conductive hydrogel microneedles, and coupled with EA stimulation promoted healing of wound tissue and peripheral nerves. This strategy regulated both local and systemic inflammation while alleviating depressive-like behaviors in diabetic rats, providing a new clinical perspective for the treatment of diabetes-related and emotional disorders. We introduce a treatment method that combines electroacupuncture at the Dazhui (GV14) acupoint with conductive polyphenol hydrogel microneedles to promote diabetic wound healing. Electroacupuncture at GV14 inhibits systemic inflammation, while conductive polyphenol hydrogel microneedles coupled with electrical stimulation regulate the local immune microenvironment of the wound over the long term. By disrupting the inflammation-depression cycle, this method effectively promotes diabetic wound healing. • Conductive polyphenol microneedles modulate the local immune microenvironment. • Electroacupuncture at Dazhui acupoint (GV14) inhibits systemic inflammation. • Microneedles with electroacupuncture accelerate wound healing in diabetic rats. • This strategy promotes wound healing and alleviates inflammation-related depression.