Dual-Functionalized Extracellular Vesicles Promote Brain Repair and Remodeling Following Ischemic Stroke in Mice

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Neuroscience

Background:

• Ischemic stroke causes significant disability and mortality globally.
• Limited endogenous repair capacity hinders recovery after stroke.
• Novel therapeutic strategies are needed to promote neurovascular regeneration.

Purpose of the Study:

• To develop a dual-functionalized extracellular vesicle (EV) platform for enhanced post-stroke repair.
• To improve targeting specificity and therapeutic efficacy of EVs for ischemic stroke.
• To leverage EVs for promoting neurovascular regeneration.

Main Methods:

• Neural stem cell-derived EVs were bioengineered using bio-click chemistry.
• RGD peptides were displayed on EVs for selective binding to integrin αVβ3.
• Vascular endothelial growth factor (VEGF) was loaded into EVs to create a synergistic effect.

Main Results:

• Engineered EVs showed a 5.2-fold increase in endothelial uptake.
• In vitro, EVs enhanced endothelial cell migration by 2.1-fold.
• In a mouse stroke model, EVs reduced infarct volume by 52.4% and improved motor function by 71.8%, promoting angiogenesis and neurogenesis.

Conclusions:

• A dual-functionalized EV system offers a potent, synergistic approach for ischemic stroke repair.
• Targeted delivery combined with VEGF loading enhances therapeutic outcomes.
• Engineered EVs show promise for translational development in neurovascular regeneration.