Ultrasound-responsive piezoelectric analgesic microspheres alleviate osteoarthritis pain

Osteoarthritis (OA) is one of the most common causes of chronic pain. However, current OA pain therapies often fail to achieve satisfactory outcomes. To effectively alleviate OA pain, ultrasound-responsive piezoelectric analgesic microspheres, constructed using ultrasound and piezoelectric nanomaterials, were developed. Barium titanate (BaTiO₃) piezoelectric nanoparticles modified by rabies virus glycoprotein (RVG) were loaded onto gelatin-methacrylate (GelMA) and hyaluronic acid-methacrylate (HAMA) composite hydrogel microspheres (GA/HA) obtained via microfluidic technology to construct analgesic microspheres (BaTiO₃-RVG@GA/HA). Under ultrasound, the analgesic microspheres can generate electrical pulses. Pain signal transmission is blocked by modulating the voltage-gated sodium channel (VGSCs) Na_v1.7, thus alleviating OA pain. In vitro studies confirmed that analgesic microspheres can effectively reduce the expression of pain-related molecules. In addition, in vivo research results showed that analgesic microspheres can significantly reduce pain-related behaviors and joint pathological damage in rats, achieving improvements in OA pain and joint injury management.