Bioinspired Electrospun Nanofibrous Dressings Loaded with Mentha-Derived Exosome-like Vesicles for Antibacterial and Immunomodulatory Burn Healing

Abstract

Deep partial-thickness burns present a significant therapeutic challenge due to susceptibility to multidrug-resistant bacterial infections and persistent inflammation. Conventional grafts and dressings often fail to address the complex "inflammatory storm" microenvironment. Herein, inspired by the traditional medicinal use of Mentha for heat dissipation and dermatitis relief, we engineered a bioactive nanofibrous dressing via the electrostatic self-assembly of poly (γ-glutamic acid) (γ-PGA) and ε-poly-L-lysine (ε-PLL), loaded with Mentha-derived exosome-like vesicles (mEVs). This biomimetic mEVs@γ-PGA@ε-PLL (mEVs@PP) scaffold mimics the extracellular matrix (ECM), providing physical protection and high porosity.Mechanistically, the sustained release of mEVs reprograms the immune microenvironment by downregulating proinflammatory cytokines (IL-1β, IL-6), while simultaneously exhibiting potent broad-spectrum antibacterial activity against S.aureus, E. coli, and P. aeruginosa. Furthermore, the dressing significantly promotes angiogenesis and accelerates reepithelialization via the HIF-1ɑ/VEGF pathway. In vivo assessments confirm that mEVs@PP enhances burn wound healing with superior tissue remodeling compared to commercial treatments. This study presents a novel "antibacterialimmunomodulatory" strategy, offering a promising, cost-effective solution for severe burn management.