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.