Abstract
The endothelium monolayer lining in the luminal side of blood vessels provides critical anti-thrombotic activities. Damage to these cells will expose a highly thrombogenic subendothelium that stimulates thrombosis. Standing on the concept of tissue engineering and ligand-receptor targeting strategy, we developed a novel biodegradable urethane-doped polyester (UPE) multifunctional targeting nanoparticle (MTN) scaffold system with dual ligands: 1) GP1b-α to target the injured arterial endothelium and subendothelium and 2) anti-CD34 antibodies to capture endothelial progenitor cells (EPCs) for endothelium regeneration. The fabricated spherical MTNs of 400 nm were shown to be biocompatible and hemocompatible. Both the in vitro and ex vivo targeting of these nanoscaffolds not only showed improved binding efficiency of MTNs onto the von Willebrand Factor (vWF) coated surfaces presented as the injured arterial walls, but also outperformed platelets for binding onto these injured sites. Our in vivo study further showed 57% neointimal hyperplasia suppression and a 70% increase in endothelium regeneration within 21 days after delivering of MTNs upon vascular injury. These results indicate that our injectable MTN nanoscaffolds show a potential non-invasive way for endothelium regeneration in situ .
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