Air Discharge Plasma-Activated Hydrosols with Phased RONS-Mediated Anti-Infection, Anti-Inflammation, and Tissue Remodeling Effects for the Integrated Treatment of Chronic Wounds

Chronic wound repair requires strategies integrating anti-infection, anti-inflammation, and tissue regeneration across wound healing stages. Nevertheless, few therapeutic approaches can incorporate all of these strategies. Although cold atmospheric plasma can regulate cell physiology and pathology through the generation of reactive oxygen and nitrogen species (RONS) and is promising in wound healing applications, how to store and deliver optimal RONS to chronic wound sites is highly challenging. Herein, the air discharge plasma-activated sodium alginate hydrosol (PAH_SA) is used to carry RONS to accomplish integrated chronic wound treatment. In vitro results demonstrate that abundant aqueous RONS are incorporated into PAH_SA by gas-liquid reactions between the plasma and sodium alginate hydrosol. PAH_SA, boasting promising RONS storage and slow-release properties, shows phased RONS-mediated sterilization, macrophage polarization regulation, and cell migration. Moreover, in the animal model with chronic wound healing, PAH_SA reduces bacterial infection through a controlled local inflammatory reaction and promotes growth factor release to stimulate tissue regeneration. Continuous delivery of RONS with gradient concentrations is biocompatible and shows no systemic toxicity. This study demonstrates that the natural decay of plasma-generated RONS can be temporally matched to the dynamic needs of the healing process, underscoring the clinical potential of plasma-activated hydrosols in integrated chronic wound treatment.