Quercetin in skin burn healing: mechanisms, advanced delivery systems, and translational perspectives

Burn injuries remain a significant global health challenge, often leading to prolonged healing, infection, and scarring. Addressing these complications requires innovative therapeutic strategies that can accelerate tissue repair and minimize adverse outcomes. Quercetin, a widely distributed plant-derived flavonoid, has emerged as a promising multi-functional agent in burn wound management. This review presents a comprehensive overview of quercetin's therapeutic potential, emphasizing its pharmacological versatility and the need for advanced topical delivery systems such as nanostructured lipid carriers and hydrogels to overcome its limited bioavailability. Quercetin's efficacy is rooted in its multi-targeted mechanisms of action. It exhibits potent antioxidant activity by directly scavenging reactive oxygen and nitrogen species and activating the Nrf2-ARE signaling pathway, thereby enhancing endogenous antioxidant defenses. Its anti-inflammatory effects are mediated through the inhibition of NF-κB and MAPK pathways, leading to the suppression of key pro-inflammatory cytokines. Quercetin also promotes angiogenesis via upregulation of vascular endothelial growth factor (VEGF), supports fibroblast proliferation and extracellular matrix remodeling, and facilitates re-epithelialization. This review consolidates dispersed experimental findings into a unified mechanistic and translational framework, highlighting why quercetin is uniquely positioned among phytochemicals for burn therapy. By integrating pharmacodynamics, formulation science, and clinical feasibility, the article clarifies current evidence gaps and outlines practical directions for therapeutic development. Such synthesis is timely because research on flavonoid-based wound therapeutics is expanding rapidly but remains fragmented across disciplines.