Gelatin methacryloyl/hyaluronic acid hydrogel for localized ropivacaine delivery alleviates neuropathic pain and supports functional recovery after spinal cord injury

Neuropathic pain caused by spinal cord injury severely compromises patients' quality of life. The clinical application of ropivacaine is limited by its short duration of action and the significant side effects associated with repeated administration. In this study, we developed a Gelatin methacryloyl/hyaluronic acid-based hydrogel (Ropi-GelMA/HA) to enable localized and controlled delivery of ropivacaine by photo-crosslinking. In a rat model of spinal cord contusion, Ropi-GelMA/HA was associated with lower Nav1.3 and TNF-α expression and higher NGF and BDNF expression, together with improved motor recovery in rats with SCI. In vitro studies further supported the hydrogel's favorable biocompatibility and controlled release behavior during the early phase after administration. Under the tested dosing regimens, Ropi-GelMA/HA was associated with reduced hepatorenal toxicity and more durable analgesic efficacy compared with free ropivacaine, resulting in prolonged analgesic effects and improved functional outcomes under localized controlled delivery conditions. These findings highlight the potential clinical utility of Ropi-GelMA/HA in the treatment of neuropathic pain following spinal cord injury.