Artificial photosynthetic H₂/O₂-producing nanosheets promote diabetic chronic wound healing through antibacterial and anti-apoptotic pathways.

Abstract

Diabetic chronic wounds represent a significant clinical challenge, characterized by bacterial biofilms, impaired vascularization, and persistent oxidative stress. While photothermal therapy (PTT) has emerged as a potential antibacterial approach, its efficacy is often constrained by limited photothermal conversion efficiency and unintended aggravation of oxidative stress. Drawing inspiration from the coordinated energy conversion and photoprotective mechanisms of natural photosynthesis, we developed a biomimetic two-dimensional H₂/O₂-producing photothermal (2D-HPT) nanosheets. This nanosheets integrate liquid-phase exfoliated CaSi₂ nanosheets functionalized with palladium nanoparticles and polyvinylpyrrolidone to execute an artificial photosynthetic cycle. Under near-infrared (NIR) light irradiation, the nanosheets exhibit an enhanced photothermal effect and hydrolytic H2 generation, thereby achieving efficient biofilm disruption. Crucially, the continuous release of H₂ and in situ catalytic production of O₂ not only mimic natural photosynthetic outputs but also programmatically activate a cell-protective mechanism. This process, analogous to non-photochemical quenching in plants, results in scavenging of reactive oxygen species (ROS), stabilization of mitochondrial membrane potential, and suppression of apoptosis. These coordinated actions significantly downregulate pro-inflammatory cytokines (IL-6/TNF-α) and promote VEGF/CD31-mediated angiogenesis, collectively accelerating the healing of infected diabetic wounds. Our work thus provides an effective strategy for chronic wound repair. STATEMENT OF SIGNIFICANCE: This study presents a biomimetic strategy for treating diabetic chronic wounds, which are clinically challenging due to bacterial biofilms and persistent oxidative stress. Inspired by natural photosynthesis, the designed two-dimensional H₂/O₂-producing photothermal nanosystem not only disrupts biofilms via enhanced photothermal effects and hydrolytic H₂ generation under NIR irradiation, but also continuously releases H₂ and catalytically produces O₂ to activate a cell-protective mechanism. This coordinated action alleviates oxidative stress, reduces inflammation, and promotes VEGF/CD31-mediated angiogenesis, collectively accelerating wound healing. The work offers an effective innovative therapeutic approach for chronic wound management.