Antioxidant-Engineered Milk-Derived Extracellular Vesicles for Accelerating Wound Healing via Regulation of The Pi3k-Akt Signaling Pathway.

Inspired by the experience of relieving inflammation in infants with milk, we have developed antioxidant-engineered milk-derived extracellular vesicles (MEVs) to evaluate their potential for accelerating wound healing. In this work, we engineered MEVs with polydopamines (PDA) using the co-extrusion method. Subsequently, we incorporated them into a Schiff-based crosslink hydrogel, forming a skin dosage form that could facilitate the wound healing process. The antioxidant properties of PDA assist in the anti-inflammatory function of engineered MEVs, while the gel provides better skin residency. The PDA@MEVs+GEL formulation exhibited excellent biocompatibility, pro-angiogenic capacity, and antioxidant ability in vitro. Furthermore, in vivo, experiments demonstrated its efficacy in wound repair and inflammation inhibition. Mechanistically, PDA@MEVs+GEL simultaneously promoted the growth, migration, and anti-inflammation of 3T3 cells by activating PI3K-AKT pathway. Moreover, PDA@MEVs+GEL exhibited enhanced functionality in promoting wound healing in vivo, attributed to its ability to inhibit inflammation, stimulate angiogenesis, and promote collagen synthesis. In conclusion, this study delves into the mechanism of MEVs and underscores the improved efficacy of engineered extracellular vesicles. Additionally, the feasibility and prospect of engineered MEVs in treating skin wounds were verified, suggesting that antioxidant-engineered MEVs could be a promising therapeutic agent for wound healing applications. This article is protected by copyright. All rights reserved.