Polycaprolactone vascular graft with epigallocatechin gallate embedded sandwiched layer-by-layer functionalization for enhanced antithrombogenicity and anti-inflammation

Abstract

Small-diameter artificial vascular grafts modified with layer-by-layer (LBL) coating show promise in reducing the failure caused by thrombosis and inflammation, but undesirable stability and bioactivity issues of the coating and payload usually limits their long-term efficacy. Herein, inspired by catechol/gallol surface chemistry, a sandwiched layer-by-layer coating constructed by polyethyleneimine (PEI) and heparin with the embedding of epigallocatechin gallate (EGCG)-dexamethasone combination was used to modify the electrospun polycaprolactone (PCL) vascular grafts. Polyphenol embedding endowed the coating with abundant intermolecular interactions between each coating components, mainly contributed by the π-π stacking, weak intermolecular cross-linking and enriched hydrogen bonding, which further enhanced the coating stability and also supported the sustained release of the payloads, like polyelectrolytes and drugs. Compared with the conventional LBL coating, the loading amounts of heparin and dexamethasone in the EGCG embedded LBL coatings doubled and the drug release could be significantly prolonged without serious initial burst. The in vitro and ex vivo assays indicated that the modified PCL vascular grafts would address impressive prolonged anti-platelet adhesion/activation and anti-fibrinogen denaturation ability. Meanwhile, the dexamethasone loading entrusted the sandwiched LBL coating with mild tissue response, in terms of inhibiting the macrophage activation. These results strongly demonstrated that the sandwiched LBL coating with EGCG embedding was an effective method to improve the patency rates of PCL small artificial vascular grafts, which could also be extended to other blood-contacting materials.