Targeting Oxidative and Immune Dysregulation in Wound Healing via Gold Nanoparticle Conjugate Chitosan

ABSTRACT A novel gold nanoparticle‐chitosan (AuNP@chitosan) composite is introduced as a potent biointerface modulator for burn trauma care. In this study, the unique interfacial characteristics of the composite are linked to its therapeutic activity, and its effects on endothelial function and immune response in severe bleeding and inflammatory models are examined. AuNP@chitosan synthesis was verified using FTIR and fluorescence, and its effects were assessed in TNF‐α‐induced HUVECs, LPS‐stimulated macrophages, and an animal model. In vitro, AuNP@chitosan protects TNF‐α‐injured human endothelial cells (HUVECs) by restoring thrombomodulin expression, reducing ROS, and relieving the upregulated hypoxia‐adaptive markers (HIF‐1α and fibronectin). Concurrently, in LPS‐stimulated RAW 264.7 macrophages, it suppresses pro‐inflammatory mediators (TNF‐α and IL‐6) while preserving COX‐1 and enhancing IL‐10 production. These cell‐specific responses reflect distinct but complementary mechanisms, vascular protection and immune regulation, which were further validated in a rat burn model. In vivo application of AuNP@chitosan dressings significantly reduced infiltration of CD4 + , CD8 + , and CD68 + immune cells in wound tissue, supporting the translational relevance of the dual in vitro findings. The integrated cell and animal studies demonstrate that AuNP@chitosan acts via redox and immune modulation to promote a pro‐healing wound environment.