4.8 Article

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

期刊

ACTA BIOMATERIALIA
卷 97, 期 -, 页码 344-359

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2019.07.057

关键词

Vascular graft; Antithrombotic peptide; Cell adhesion peptide; Hemocompatibility; Endothelialization

资金

  1. National Key R&D Program of China [2016YFC1100300]
  2. National Natural Science Foundation of China [51673145, 51873149, 31370969]
  3. International Science & Technology Cooperation Program of China [2013DFG52040]

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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 similar to 2 mm) was fabricated by electrospinning with poly(lactic acid-co-caprolactone) and gelatin, and then biofunctionalized with antithrombotic peptide with sequence LTF-PRIVFVLG (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. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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