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

## TL;DR

This paper introduces a new therapy using brain endothelial cells to repair the blood-brain barrier and deliver siRNA to treat cerebral ischemia/reperfusion injury.

## Contribution

A novel brain-targeted delivery platform using vascular bandages of endothelial cells for BBB repair and siRNA delivery.

## Key findings

- mECs target damaged cerebral vessels via VLA-4 and support BBB integrity by forming new junctions.
- OGD-treated mECs enhance siRNA delivery to damaged endothelium via CX43-mediated communication.
- Vascular bandage treatment rescued BBB function and reduced infarct area in ischemia/reperfusion injury.

## 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 p66Shc 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.

mECs restore blood–brain barrier function after cerebral ischemia–reperfusion by simultaneously targeting, supporting, and regulating the damaged vasculature. mECs home to injured cerebral vessels through interactions with highly expressed VLA‐4, reinforce endothelial integrity by forming new junctions, and, upon OGD‐SN treatment, acquire enhanced siRNA loading capacity and further improve p66Shc siRNA delivery via CX43‐mediated cellular communication.