Immunometabolic checkpoint-mediated macrophage metabolic reprogramming accelerates infected wound healing

Abstract

Immunometabolic disorders, triggered by excessive oxidative stress, lead to macrophage dysfunction, consequently impeding the healing of infected wounds. The uncontrolled accumulation of reactive oxygen species (ROS) in infected wounds is primarily attributed to persistent bacterial infections, excess exudate, and hypoxia. Herein, an immunometabolic checkpoint-mediated macrophage metabolic reprogramming strategy based on a nanofiber aerogel loaded with catalase (CAT) and tannic acid (TA) is proposed. The three-dimensional porous network of the nanofiber aerogel effectively absorbs exudates, maintains wound dryness, and prevents tissue saturation. CAT catalyzes oxygen generation, alleviates hypoxia, and reduces ROS, while TA acts as a natural antioxidant and antibacterial agent, collaboratively mitigating oxidative stress and bacterial infections. More importantly, the CAT-TA nanofiber aerogel, as an immunometabolic checkpoint regulator, can reshape the glutathione (GSH) metabolic pathway, enhancing intrinsic antioxidative capacity, allowing the reversion of macrophage functions, and ultimately promoting wound healing. This macrophage metabolism therapy (MMT), centered on the modulation of immunometabolic checkpoint, effectively enhances the regenerative capacity of infected wounds and provides a pioneering perspective for the treatment of regeneration disorders in infected tissues.