The ability to supply suitable blood vessel system is a major challenge for artificial thick tissue engineering. Angiogenesis is a key point during the process of microvascular formation. Many bioactive molecules such as extra cellular matrix (ECM) proteins and adhesion peptides derived from the ECM are applied to promote angiogenesis. In this work, two adhesion peptides, YIGSR and REDV, were selected to modify sodium alginate (ALG) to obtain YIGSR- and REDV-alginate conjugates (ALG-YIGSR, and ALG-REDV, respectively). We mixed the two peptide-conjugates together in a series of concentration ratios to prepare bioactive surfaces for in vitro studies and hydrogel scaffolds for in vivo studies. In vitro studies showed that surfaces modified with 1.09 pmol/mm 2 peptide had the best affinity to human umbilical vein endothelial cells (HUVECs) than that with high or low concentrations of peptides. In addition, surfaces modified with dual peptides could significantly promote HUVECs proliferation, where ALG-YIGSR:ALG-REDV at a mole ratio of 5:1 exhibited the best enhancement ability. Furthermore, the in vivo angiogenesis results demonstrated that hydrogel scaffolds composed of mixed ALG-YIGSR and ALG-REDV at the 5:1 ratio had angiogenic induction potential by stimulating new blood vessel formation, and showed higher blood vessel density than scaffolds composed of a single peptide. These results demonstrated that a mixed combination of peptide alginate conjugates could be a potential scaffold to stimulate and induce angiogenesis in tissue engineering applications.
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.
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