Multifunctional Apoptotic Bodies Engineered by Magnesium Oxide Nanoparticles for Synergistic Ischemic Skin Flap Therapy

Abstract Engineered extracellular vesicles (EVs) loaded with therapeutic cargos offer promise for therapeutic applications in various diseases. Yet, engineering EVs with optimal functions presents a significant challenge that necessitates the precise selection of functionally specialized vesicles and a proper engineering strategy. Here, magnesium oxide‐incorporated apoptotic bodies (MgO@ABs) are developed by isolating ABs from human umbilical vein endothelial cells (HUVECs) after MgO exposure. MgO@ABs mitigate tert‐butyl hydroperoxide (TBHP) induced dysfunction in HUVECs and promote M1 to M2 macrophage polarization in vitro. When administered in vivo via injection into ischemic skin flaps, MgO@ABs effectively stimulate angiogenesis, reduce oxidative stress, and suppress inflammation, thereby improving flap survival. Furthermore, RNA‐seq analysis reveals that MgO@ABs potentially enhance flap survival by activation of the PI3K‐Akt axis. This study highlights a promising approach for treating ischemic skin flaps and offers valuable insights and inspiration for advancing tissue engineering research centered on ABs.