Adenosine-loaded adhesive microfluidic hydrogel microspheres stimulate acupoint activation for pain management

Pain represents a significant public health challenge with substantial clinical and economic burdens. While pharmacotherapy remains a mainstay of pain management, its utility is limited by adverse side effects and the potential for dependency. Acupuncture has shown great potential in pain management through its ability to induce analgesic effects via acupoint stimulation. However, its poor specificity and ill-defined stimulation parameters compromise therapeutic specificity and reproducibility. Herein, we developed a biomaterial-based acupoint activation strategy for pain management. Adhesive polydopamine-coated hydrogel microspheres were fabricated using microfluidic techniques for accurate attachment and activation of acupoints. Adhesive hydrogel microspheres loaded with adenosine can slowly release exogenous adenosine at the ST36 acupoint to simulate the analgesic effect of acupuncture. In vitro and in vivo studies demonstrated that single-dose administration of adhesive microspheres can effectively target acupoints, elevate mechanical pain thresholds, and provide systemic anti-inflammatory effects for up to 7 days. Overall, the proposed adhesive hydrogel microsphere system offers a new perspective on acupuncture practice and pain management.