In Situ Re-endothelialization via Multifunctional Nanoscaffolds

[Image: see text] The endothelium monolayer lining in the luminal side of blood vessels provides critical antithrombotic functions. Damage to these cells will expose a highly thrombogenic subendothelium, which leads to pathological vascular changes. Using combined tissue engineering and ligand–receptor targeting strategy, we developed a biodegradable urethane-doped polyester (UPE) multifunctional targeting nanoparticle (MTN) scaffold system with dual ligands: (1) glycoprotein 1b (GP1b) to target the injured arterial endothelium and subendothelium and (2) anti-CD34 antibodies to capture endothelial progenitor cells for endothelium regeneration. The fabricated spherical MTNs of 400 nm were found to be cytocompatible and hemocompatible. Both the in vitro and ex vivo targeting of these nanoscaffolds not only showed binding specificity of MTNs onto the von Willebrand factor -coated surfaces that simulate the injured arterial walls but also competed with platelets for binding onto these injured sites. Further in vivo study has revealed that a single delivery of MTNs upon vascular injury reduced neointimal hyperplasia by 57% while increased endothelium regeneration by ∼60% in 21 days. These results support the promise of using MTN nanoscaffolds for treating vascular injury in situ.