Search

Surface modification by conjugating biomolecules has been widely proved to enhance biocompatibility of small-caliber artificial vascular grafts. In this study, we aimed at developing a multifunctional vascular graft that provides not only good hemocompatibility but also in situ rapid endothelialization. Herein, a vascular graft (inner diameter ∼2 mm) was fabricated by electrospinning with poly(lactic acid-co-caprolactone) and gelatin, and then biofunctionalized with antithrombotic peptide with sequence LTFPRIVFVLG (ACH 11 ) and cell adhesion peptide with sequence CAG through adhesive poly(dopamine) coating. We developed this graft with the synergistic properties of low thrombogenicity and rapid endothelialization. The successful grafting of both CAG and ACH 11 peptides was confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface micromorphology of the modified surfaces was observed by field emission scanning electron microscopy. Our results demonstrated that the multifunctional surface suppressed the denaturation of absorbed fibrinogen, hindered coagulation factor Xa activation, and inhibited platelet adhesion and aggregation. Importantly, this modified surface could selectively enhance endothelial cells adhesion, proliferation and release of nitric oxide. Upon in vivo implantation of 6 weeks, the multifunctional vascular graft showed improved patency and superior vascular endothelialization. Overall, the results effectively demonstrated that the co-immobilization of ACH 11 and CAG provided a promising method for the improvement of hemocompatibility and endothelialization of vascular grafts. STATEMENT OF SIGNIFICANCE: Electrospun small-caliber vascular grafts are increasingly used to treat cardiovascular diseases. Despite their success related to their good biodegradation and mechanical strength, they have some drawbacks, such as low hemocompatibility and endothelialization. The single-function ligands are insufficient to modify surface with both good hemocompatibility and rapid endothelialization simultaneously. Therefore, we functionalized electrospun vascular graft by novel antithrombotic peptide and cell-adhesive peptide to construct superior anticoagulation and ECs-selective adhesion surface in present study. The multifunctional vascular grafts benefit for high long-term patency and rapid endothelialization., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Blood-contacting materials with antiplatelet aggregation and anticoagulant properties are in great demand in biomedical field. Herein, hydrophilic poly(ethylene glycol) (PEG) and antithrombotic peptide ACH 11 were coimmobilized onto Au to develop a multifunctional surface with remarkable hemocompatibility, antiprotein adsorption, antiplatelet aggregation, anticoagulant properties, and good histocompatibility. PEG can not only help the surface resist nonspecific protein adsorption and improve its hemocompatibility but also be a benefit for the immobilized ACH 11 to maintain its bioactivity in plasma. The anticoagulant peptide ACH 11 can endow the surface with the ability of activated coagulation factor Xa (FXa) inhibition and antiplatelet aggregation activities. Au was first aminated with 2-aminoethanethiol through strong Au-S bond, and then it was reacted with PEG-ACH 11 through active ester chemistry to prepare the multifunctional surface Au-PEG-ACH 11 , among which the heterobifunctional PEG served as a linker to immobilize antithrombotic ACH 11 . The surface chemical structure and composition quantified by attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy convinced us of the successful preparation of the PEG-ACH 11 modified Au surface. The surface micromorphology and topography of the modified surfaces were observed by field emission scanning electron microscopy and atomic force microscopy. The good hydrophilicity of the modified Au surface was confirmed by water contact analysis. Enzyme immunoassay analysis demonstrated that the activation level of FXa in plasma after incubation with Au-PEG-ACH 11 was obviously lower than that in control groups. In vitro hemocompatibility evaluation, including hemolysis rate, denaturation of adsorbed fibrinogen, and platelet adhesion and activation, indicated that Au-PEG-ACH 11 possessed good hemocompatibility. In vivo subcutaneous implantation assay also confirmed the milder tissue response of Au-PEG-ACH 11 . These results indicated that the multifunctional surface has great potential for biomedical application.