Development of a Polyester Coating Combining Antithrombogenic and Cell Adhesive Properties: Influence of Sequence and Surface Density of Adhesion Peptides Samantha Noel, † Ahmed Hachem, ‡ Yahye Merhi, ‡ and Gregory De Crescenzo* ,† † Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biome ́ dicales, Bio-P 2 Research Unit, E ́ cole Polytechnique de Montre ́ al, P.O. Box 6079, succ. Centre-Ville, Montré al (QC), Canada H3C 3A7 ‡ Universite ́ de Montre ́ al, Montreal Heart Institute, 5000 Belanger Est, Montre ́ al (QC), Canada H1T 1C8 * S Supporting Information ABSTRACT: Biofunctionalization strategies have been devel- oped to improve small-diameter vascular grafts. However, a fully successful coating featuring antithrombogenic properties while allowing for endothelialization has not been achieved yet. In this report, we explored the combination of low-fouling polyethylene glycol (PEG) and adhesion peptides, namely, RGD, YIGSR, and REDV, grafted on top of polyvinylamine (PVAm)-coated polyester. The peptides were grafted over a wide range of density (ca. 20-2000 pmol/cm 2 ) on top of a dense PEG underlayer. The coating performances were assessed through HUVEC adhesion, platelet attachment, and protein adsorption, which were all drastically diminished on PEG-coated samples. RGD exhibited the expected high adhesive properties, toward both HUVEC and platelets. REDV had no effect neither on platelet attachment, as expected, nor on HUVEC adhesion, in contrast with previous reports. YIGSR was the most promising sequence even though its combination with other agents should be explored to further decrease thrombogenicity for vascular graft applications. ■ INTRODUCTION In recent years, the biomaterials community has embraced the idea that implant fate is determined at the interface between the foreign material and its environment. Control over the biomaterial surface properties is therefore a key starting point that has been, and still is, sought by many groups, including ours. 1 Particularly, in the design of vascular conduits, fine- tuning the properties of the inner surface is essential, as the latter should mimic the endothelium as closely as possible. Considering the complexity of the endothelium functions, 2 this task mostly implies seeking for a complete endothelialization of the vascular graft. Complete endothelialization through endothelial cell (EC) seeding takes weeks of maturation to be achieved prior implantation, making it clinically imprac- tical. 3-5 Accordingly, recent reports had been focused on single-stage EC seeding (ex situ) without complete maturation or homing (in situ) of endothelial progenitor cells (EPCs) on adequately modified surfaces. 5-8 Considering such strategies where the sought endothelium lining is either incomplete or inexistent at the implantation, graft interactions with blood components must be carefully looked at to prevent immunogenic response, thrombogenicity, and intimal hyper- plasia. 5 Altogether, relevant surface modification of the biomaterial must be carried out. First and foremost, the substrate has to be enriched with adhesive cues that will allow ECs (or EPCs) to quickly attach, spread, and strongly adhere to resist disruptive forces such as blood shear stress. Prior to neo- endothelium completion, the designed surface modification should be speci fic enough to prevent adsorption of thrombogenic materials (proteins, platelets) as well as adhesion and subsequent proliferation of smooth muscle cells (SMCs) to avoid hyperplasia. Such a controlled and specific functionaliza- tion can only be achieved by the tethering of carefully chosen biomolecules. 9 This biofunctionalization generally relies on three simple questions: Which molecules should be tethered to the surface? How to tether them? What molecule density would provide the adequate EC adhesion strength? Numbers of biomolecules have been isolated and grafted onto materials to mediate cell adhesion. Most of them are extracellular matrix (ECM) proteins (e.g., collagen, fibronectin, vitronectin, laminin) as well as peptides derived from them. 1,6 Compared to whole proteins, the use of peptides allows for higher control over the cell response as well as minimized immunogenicity, in addition to many advantages related to their synthesis, handling, and grafting. 10,11 The tripeptide RGD is the main adhesive domain of many ECM proteins (e.g., Received: February 16, 2015 Revised: April 9, 2015 Article pubs.acs.org/Biomac © XXXX American Chemical Society A DOI: 10.1021/acs.biomac.5b00219 Biomacromolecules XXXX, XXX, XXX-XXX