Dual-Action flavonol carbonized polymer dots spray: Accelerating burn wound recovery through immune responses modulation and EMT induction

Abstract

Effective immune homeostasis modulation and re-epithelialization promotion are crucial for accelerating burn wound healing. Cell migration is fundamental to re-epithelialization, with epithelial-mesenchymal transition (EMT) as a key mechanism. A sustained inflammatory environment or impaired macrophage transition to M2 phenotype can hinder pro-resolving cytokine activation, further delaying the recruitment, migration, and re-epithelialization of epidermal cells to the injury site, ultimately compromising wound healing. Herein, the bioactive flavonol quercetin is transformed into pharmacologically active carbonized polymer dots (Qu-CDs) spray with high water dispersibility, permeability and biocompatibility for full-thickness skin burns treatment. Qu-CDs spray can efficiently initiate macrophage reprogramming and promote the transition of macrophages from M1 to M2 phenotype, modulating immune responses and facilitating the shift from the inflammatory phase to re-epithelialization. Additionally, Qu-CDs spray can promote cell migration and re-epithelialization of wound edge epithelial cells by inducing an EMT process without growth factors, further accelerating the reconstruction of the normal epidermal barrier. Mechanistically, Qu-CDs spray activates the smad1/5 signaling pathway for promoting the EMT phenotype of wound edge epithelial cells. Overall, this study facilitates the construction of novel spray dosage form of pharmacologically active carbonized polymer dots with desired bioactivities for effective wound healing.