MicroRNA-engineered extracellular vesicles for burn wound repair: burn-specific design and translational perspectives

Abstract

Burn wound healing remains a major clinical challenge. Mesenchymal stem cell-derived extracellular vesicles engineered to deliver defined microRNA cargo or modulate endogenous microRNA profiles have emerged as promising cell-free therapeutics, but native extracellular vesicle preparations remain constrained by low yield, heterogeneity, insufficient targeting, and incomplete cargo control. Moreover, much of the current evidence still comes from non-burn wound models. This review presents a burn-oriented framework that aligns upstream parental-cell programming, downstream vesicle modification, and biomaterial-assisted delivery with key burn-specific barriers, including burn depth, eschar, infection, hypoxia, systemic inflammation, inhalation injury, grafting requirements, and temporal immune dysregulation across the systemic inflammatory response syndrome-to-compensatory anti-inflammatory response syndrome transition. We also discuss translational requirements that are often underemphasized in general wound-healing reviews, including dose scaling for large total body surface area burns, repeat application, compatibility with debridement and grafting, storage and thawing in burn centers, sterility, use in infected wounds, and whether local extracellular vesicle delivery can mitigate systemic dysfunction. Overall, microRNA-engineered extracellular vesicles are a versatile platform for burn wound repair; however, clinical translation remains speculative without large-animal, infected-burn, grafting, long-term scar, and human safety data.