A wearable spiral ultrasound patch for focused ultrasound peripheral neuromodulation of diabetic neuropathic pain

<h2>Summary</h2> Diabetic foot disease, a severe complication of diabetes, frequently results in diabetic neuropathic pain, reducing quality of life and raising amputation risk. Current therapies lack efficacy and risk side effects. Here, we report a first-of-its-kind wearable spiral ultrasound patch for focused ultrasound peripheral neuromodulation to alleviate diabetic neuropathic pain. This stretchable ultrasound device reliably delivers focused ultrasound to peripheral nerves. Ultrasound elements are arranged in a phyllotaxis spiral pattern, enhancing transmitted acoustic focus performance and suppressing grating and side lobes. Using a diabetic foot rat model, peripheral neuropathy is confirmed through behavioral assessments of mechanical allodynia and heat hyperalgesia, which show significant pain relief after 2 weeks of ultrasound treatment, alongside improved nerve conduction velocity. Biological safety tests indicate no damage on nerve tissues or cells. Our approach offers a non-invasive solution for alleviating diabetic neuropathic pain and provides critical insights into its mechanisms, paving the way for more effective therapies.