Dual-wavelength-responsive GMMC-Pdots-Ag hydrogel for spatiotemporally controlled photothermal and hydrogen therapy of infected liver and skin defects.

An innovative dual-wavelength-responsive GMMC-Pdots-Ag hydrogel was fabricated for the treatment of polymicrobial-infected liver and skin defects. The hydrogel is based on a dynamic double-network architecture composed of gelatin methacryloyl (GelMA), O-carboxymethyl chitosan (O-CMC), and 4-arm poly(ethylene glycol) benzaldehyde (4-arm-PEG-DF), co-loaded with PtOEP-doped T2-DPPT@NH2 polymer dots (Pdots) and L-histidine-stabilized silver nanoparticles (His-Ag NPs). Upon exposure to near-infrared (NIR) radiation at 808 nm, the Pdots induce a localized photothermal effect (PTT). Combined with the weakly alkaline microenvironment and temperature increase, this effect triggers the controlled release of Ag⁺. This dual response enables rapid antibacterial activity and biofilm eradication during the acute stage of inflammation. During the subsequent repair phase, 380 nm near-ultraviolet (NUV) light activates the Pdots to catalytically produce hydrogen (H2). The generated H2 selectively scavenges cytotoxic reactive oxygen species (ROS), especially ·OH and •O2-, and inhibits M1 macrophage polarization through modulation of the NOD-associated MAPK and AP-1 signaling pathways. As a result, it exerts potent anti-inflammatory and antioxidant effects. H2 generation, together with the oxidation by-products, further promotes the release of Ag⁺, creating a self-propagating therapeutic cycle. In vivo studies using skin and liver infection models demonstrated accelerated wound closure, reduced inflammatory infiltration, enhanced angiogenesis, and improved tissue regeneration. Biocompatibility and biosafety tests further validated the hydrogel's potential for biomedical applications. The concept of "one material with three functions," integrating PTT, H2 therapy, and Ag⁺-mediated antimicrobial activity, enables precise, stage-specific, and microenvironment-responsive intervention. This approach highlights the potential of the hydrogel as a platform for smart wound management and clinical translation.