Smart response CO hydrogel "battling" bacterial biofilms and inflammation associated with wounds

Bacterial infections accompanied by excessive inflammatory responses and bleeding can significantly impede wound healing, with biofilms further complicating treatment and reducing its effectiveness. Herein, an intelligent carbon monoxide (CO) gas-releasing and hemostatic hydrogel was developed, composed of carboxymethyl chitosan (CMCS), hyaluronic acid (HA), copper-doped mesoporous Prussian blue nanoparticles (named as CuHMPB NPs), luteolin, and Mn2(CO)10, through chemical and physical cross-linking. Cu-HMPB is loaded with luteolin, a natural flavonoid, and covalently bonded with the temperature-sensitive CO donor Mn2(CO)10. By utilizing cross-linking agents, CMCS and HA are physically loaded with Cu-HMPB@Lu@Mn nanoparticles (named as Cu-HLM NPs) to form the composite hydrogel (named as CuHLM/C-H). Under near-infrared (NIR) irradiation, the CuHLM/C-H hydrogel exhibited excellent photothermal capabilities and enabled on-demand CO gas release. The CO gas effectively penetrated mature biofilms and promoted their dissipation, synergizing with the photothermal effect to efficiently eradicate biofilms. The antioxidant properties of luteolin effectively pre- vents redox imbalance. Additionally, the CuHLM/C-H hydrogel demonstrated significant hemostatic effects in mouse liver and tail hemorrhage models. Collectively, the combination of gas therapy and photothermal therapy shows exceptional potential for addressing clinical issues caused by biofilms and associated inflammation.