Nanocomposite hydrogel to integratively inhibit bacteria and inflammation for infected wound repair

Bacterial infection and the resulting inflammatory microenvironment are two critical factors to significantly inhibit tissue regeneration and even lead to wound deterioration. In this study, antisense oligonucleotides modified gold‑palladium alloy nanoparticles with hydrogen encapsulation (APDH) were prepared and then loaded in a biodegradable hyaluronic acid/alginate hydrogel to integratively inhibit bacteria and inflammation via cascaded photothermal therapy (PTT), photoinduced hydrogen therapy and gene-immunological therapy for infected wound repair. This nanocomposite hydrogel (HS@APDH) gradually decomposes in the infection microenvironment (low pH value and abundant hyaluronidase), thereby achieving continuous APDH release. Under 808 nm near-infrared (NIR) irradiation, APDH achieves a high photothermal conversion efficiency, raising the local temperature to 58 °C within 5 min, while releasing hydrogen to inhibit the energy metabolism of bacteria and clear reactive oxygen species (ROS), increasing the antibacterial effect against Staphylococcus aureus to 99 %. Meanwhile, the light-induced APDH can act on excessive M1-type macrophages, capture miR-155 to promote M1-type macrophages polarization to M2-type macrophages, successfully establishing an anti-inflammatory microenvironment. In vivo mouse models demonstrated that HS@APDH can accelerate wound healing, with a wound closure rate of 99 % on the 9th day, significantly superior to the control group (closure rate of 88.4 %), confirming its potential in infectious wound repair.