Biohybrid microalgae living hydrogel with self-oxygenation and green-synthesized zinc nanoparticles to combat multidrug-resistant infections via transcriptional reprogramming.

Abstract

Multidrug-resistant (MDR) infections pose a formidable threat to global health, with hypoxia and infection representing two major interconnected challenges that impede wound healing. Current therapeutic approaches often fail to provide sustained oxygen supply or effectively combat MDR bacteria. Herein, we developed an innovative living hydrogel dressing to address these issues. Chlorella vulgaris (CV) was employed as a bioreactor for the green synthesis of zinc oxide nanoparticles (ZnO NPs). The resulting CV/Zn complex was encapsulated within an alginate hydrogel matrix to form CV/Zn@Gel. This composite system enables continuous and stable oxygen release through microalgal photosynthesis. Meanwhile, CV/Zn@Gel confers potent antibacterial activity against MDR pathogens by inducing oxidative macromolecular damage and eliciting broad transcriptional reprogramming. In vitro assessments confirmed that CV/Zn@Gel significantly promotes cell proliferation and migration while exhibiting robust antibacterial efficacy. In a murine model of MDR-infected wounds, CV/Zn@Gel dressing markedly accelerated wound healing by alleviating hypoxia, reducing bacterial load, and modulating the immune response. Collectively, this work presents a novel and potent strategy for managing multidrug-resistant infections.