Analgesic-loaded NIR-II photothermal hydrogel for efficient anti-infection and precise pain management in wounds

Photothermal therapy (PTT) is widely recognized for the treatment of infected wounds. However, the wound hyperpathia caused by infection and heat from PTT is often overlooked, which might affect wound healing significantly. In this study, we systematically investigate the management of pain in bacteria-infected wounds using PTT, and develop a photothermal antibacterial hydrogel capable of sustained and controlled analgesia system (STB-Lid Gel), aiming to simultaneously achieve efficient anti-infection and precise pain management. STB-Lid Gel is constructed from a silk fibroin (SF) hydrogel matrix co-loaded with lidocaine (Lid) as an analgesic and supramolecular stable radicals (TPT-B₁₂) as a novel second near-infrared-window (NIR-II) photothermal agent. During the treatment phase, the sustained release of Lid stored in STB-Lid Gel extends localized analgesic effects beyond 30 h. Under NIR-II laser irradiation, STB-Lid Gel mediates PTT for bacterial eradicating and enhancement of Lid release. These dual effects of anti-infection and pain management, effectively eradicates bacteria, alleviates PTT-induced acute pain, reduces local inflammation, and ultimately accelerates wound healing. This innovative approach highlights the importance of pain relief from PTT-associated acute pain in healing processes, presenting a viable strategy for combining antibacterial and analgesic treatment in infected wounds.