Near-Infrared Responsive Injectable Thermosensitive Hydrogel Sequentially Releases Dexmedetomidine and Ropivacaine for Postoperative Pain Management

Postoperative pain poses significant challenges for patients, with insufficient management leading to adverse outcomes. The efficacy of local anesthetics is often limited by short action duration and the need for repeated administration. To address these limitations, we developed a near-infrared (NIR) responsive injectable nanocomposite hydrogel (MSNs-Rop@PDA/Gel-DEX) that enables sustained, controllable local anesthetic delivery. In this system, ropivacaine-loaded, polydopamine-modified mesoporous silica nanoparticles were incorporated into a dexmedetomidine-loaded F127 hydrogel matrix. In vitro characterizations demonstrated that the hydrogel possesses excellent injectability and photothermal conversion efficiency. The system exhibited a distinct sequential release profile: DEX was preferentially released (90.4% in 24   h) to induce vasoconstriction, thereby reducing systemic diffusion, while ropivacaine was released in a sustained manner that could be pulsatile-triggered by NIR irradiation. Cytotoxicity assays confirmed high cell viability (>92%). In vivo experiments using a rat sciatic nerve block model showed that the composite hydrogel significantly extended the duration of analgesia to approximately 48   hours, far surpassing the effect of ropivacaine alone. Furthermore, in vivo fluorescence imaging confirmed that the vasoconstrictive effect of DEX and the NIR trigger effectively prolonged drug retention. Histological analyses of the sciatic nerves and major organs revealed gradual biodegradation of the hydrogel and confirmed satisfactory biosafety with no evidence of neurotoxicity or significant inflammatory response. Together, these results establish that the hydrogel composite provides synergistic, persistent, and controllable analgesia, demonstrating substantial clinical potential.