Endothelial Cell‐Based Vascular Bandages for Blood–Brain Barrier Repair and Targeted siRNA Delivery

ABSTRACT Changes in the blood‐brain barrier (BBB) are key targets for mitigating cerebral ischemia/reperfusion injury. The rapid progression of reperfusion injury necessitates the development of carriers that target and regulate early BBB disruption, while supporting its structure and function during BBB recovery. This study proposes the use of brain microvascular endothelial cell (mECs)‐based vascular bandages carrying siRNAs to simultaneously target, support, and regulate the damaged BBB. Specifically, mECs can target damaged cerebral blood vessels after intravenous injection by interacting with the highly expressed very late antigen ‐ 4 (VLA‐4) in the vessels. Furthermore, by covering the cerebral blood vessels and forming new junction proteins with the vascular endothelium, mECs support the permeability and structural integrity of the vasculature. Additionally, oxygen‐glucose deprivation‐treated mEC culture supernatants (OGD‐SN) can promote connexin 43 (CX43) expression, facilitating the delivery of therapeutic p66 Shc siRNA to the damaged endothelium for BBB regulation. Ultimately, vascular bandage treatment rescued BBB function, alleviated reperfusion injury, and reduced the infarct area. Our study offers a new therapeutic strategy and a novel brain‐targeted delivery platform for treating cerebral ischemia/reperfusion injury.