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

This study presents a biomaterial-based acupoint activation strategy. An adhesive micro/nano hydrogel microsphere system is developed for pain management through precise attachment and activation of acupoints. • Micro/nano adhesive hydrogel microspheres stimulated acupuncture practice. • Adhesive hydrogel microspheres activated acupoints through sustained adenosine delivery and controlled release. • Hydrogel microspheres induced long-term analgesic effects by single-dose administration. • Acupoint activation via hydrogel microspheres decreased systemic inflammatory levels. 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.