Hydrogel-Based Sequential Photodynamic Therapy Promotes Wound Healing by Targeting Wound Infection and Inflammation.

Impaired wound healing remains a significant clinical challenge, often exacerbated by bacterial infections and persistent inflammation. Photodynamic therapy (PDT) has demonstrated efficacy in combating bacterial infections; however, its utility in wound healing is limited due to its inability to address inflammation. To overcome this limitation, we have developed a PDT-based sequential therapy. Our approach effectively eliminates bacteria by generating sufficient reactive oxygen species and nitric oxide (NO). It subsequently mitigates inflammation through sustained NO release and oxygen delivery. Additionally, we incorporated a pH-sensitive indicator to enable a sequential therapeutic schedule, optimizing the timing of antibacterial and anti-inflammatory interventions during wound healing. We demonstrate that this therapy enhances anti-infection efficacy, alleviates wound inflammation, and fosters a supportive environment for skin and superficial skeletal muscle repair in mouse, rabbit, and pig models. Collectively, our findings highlight the transformative potential of this strategy for advancing PDT in the treatment of wound healing.