Coaxial-printed small-diameter polyelectrolyte-based tubes with an electrostatic self-assembly of heparin and YIGSR peptide for antithrombogenicity and endothelialization

Abstract

Low patency ratio of small-diameter vascular grafts remains a major challenge due to the occurrence of thrombosis formation and intimal hyperplasia after transplantation. Although developing the functional coating with release of bioactive molecules on the surface of small-diameter vascular grafts are reported as an effective strategy to improve their patency ratios, it is still difficult for current functional coatings cooperating with spatiotemporal control of bioactive molecules release to mimic the sequential requirements for antithrombogenicity and endothelialization. Herein, on basis of 3D-printed polyelectrolyte-based vascular grafts, a biologically inspired release system with sequential release in spatiotemporal coordination of dual molecules through an electrostatic self-assembly was first described. A series of tubes with tunable diameters were initially fabricated by a coaxial extrusion printing method with customized nozzles, in which a polyelectrolyte ink containing of ε-polylysine and sodium alginate was used. Further, dual bioactive molecules, heparin with negative charges and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide with positive charges were layer-by-layer assembled onto the surface of these 3D-printed tubes. Due to the electrostatic interaction, the sequential release of heparin and YIGSR was demonstrated and could construct a dynamic microenvironment that was thus conducive to the antithrombogenicity and endothelialization. This study opens a new avenue to fabricate a small-diameter vascular graft with a biologically inspired release system based on electrostatic interaction, revealing a huge potential for development of small-diameter artificial vascular grafts with good patency.