: Implementation of small-diameter tissue-engineered vascular grafts (TEVGs) into clinical
practice is still delayed due to the frequent complications, including thrombosis, aneurysms, neointimal hyperplasia, calcification, atherosclerosis, and infection. Here, we conjugated a vasodilator/platelet inhibitor, iloprost, and an antimicrobial cationic amphiphilic drug, 1,5-bis-(4-tetradecyl1,4-diazoniabicyclo [2.2.2]octan-1-yl) pentane tetrabromide, to the luminal surface of electrospun
poly(ε-caprolactone) (PCL) TEVGs for preventing thrombosis and infection, additionally enveloped
such TEVGs into the PCL sheath to preclude aneurysms, and implanted PCLIlo/CAD TEVGs into the
ovine carotid artery (n = 12) for 6 months. The primary patency was 50% (6/12 animals). TEVGs
were completely replaced with the vascular tissue, free from aneurysms, calcification, atherosclerosis and infection, completely endothelialised, and had clearly distinguishable medial and adventitial layers. Comparative proteomic profiling of TEVGs and contralateral carotid arteries found that
TEVGs lacked contractile vascular smooth muscle cell markers, basement membrane components, and proteins mediating antioxidant defense, concurrently showing the protein signatures of upregulated protein synthesis, folding and assembly, enhanced energy metabolism, and macrophagedriven inflammation. Collectively, these results suggested a synchronised replacement of PCL with
a newly formed vascular tissue but insufficient compliance of PCLIlo/CAD TEVGs, demanding their testing in the muscular artery position or stimulation of vascular smooth muscle cell specification after the implantation.