Co-immobilization of ACH11 antithrombotic peptide and CAG cell-adhesive peptide onto vascular grafts for improved hemocompatibility and endothelialization

Abstract

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 (ACH₁₁) 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 ACH₁₁ 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 ACH₁₁ 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.

Keywords: Antithrombotic peptide; Cell adhesion peptide; Endothelialization; Hemocompatibility; Vascular graft.