title: Conjugation with RGD Peptides and Incorporation of Vascular Endothelial Growth Factor Are Equally Efficient for Biofunctionalization of Tissue-Engineered Vascular Grafts.
abstract: The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine-glycine-aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31⁺/CD34⁺/vWF⁺ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31⁺CD34-vWF⁺ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31⁺/CD34⁺ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. antonova.la@mail.ru.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Antonova
authors.affiliation: Centre for Nanotechnology and Regenerative Medicine, UCL Division of Surgery and Interventional Science, University College London, UCL Medical School Building, 21 University Street, London WC1E 6AU, UK. a.seifalian@gmail.com.|NanoRegMed Ltd., 20-22 Wenlock Road, London N1 7GU, UK. a.seifalian@gmail.com.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. antonkutikhin@gmail.com.
authors.forename: Anton G
authors.initials: AG
authors.lastname: Kutikhin
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. sevostyanova.victoria@gmail.com.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Sevostyanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. matveeva_vg@mail.ru.
authors.forename: Vera G
authors.initials: VG
authors.lastname: Matveeva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. telella@mail.ru.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Velikanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. a.mir.80@mail.ru.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Mironov
authors.affiliation: Kemerovo Cardiology Dispensary, Sosnovy Boulevard 6, Kemerovo 650002, Russia. reception@kemcardio.ru.
authors.forename: Amin R
authors.initials: AR
authors.lastname: Shabaev
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. bio.tvg@mail.ru.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Glushkova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. sergeewa.ew@yandex.ru.
authors.forename: Evgeniya A
authors.initials: EA
authors.lastname: Senokosova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. v.georgiy@mail.ru.
authors.forename: Georgiy Yu
authors.initials: GY
authors.lastname: Vasyukov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. leonora92@mail.ru.
authors.forename: Evgeniya O
authors.initials: EO
authors.lastname: Krivkina
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. keu-73@mail.ru.
authors.forename: Andrey Yu
authors.initials: AY
authors.lastname: Burago
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. jackie1970@mail.ru.
authors.forename: Yuliya A
authors.initials: YA
authors.lastname: Kudryavtseva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. olb61@mail.ru.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Barbarash
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Boulevard 6, Kemerovo 650002, Russia. director@kemcardio.ru.
authors.forename: Leonid S
authors.initials: LS
authors.lastname: Barbarash
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002448:Cell Adhesion; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology; D055767:Immobilized Proteins / Q000737:chemistry*; D008297:Male; D009842:Oligopeptides / Q000737:chemistry*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D017208:Rats, Wistar; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
chemical_list: D018952:Antigens, CD34; D020099:Coated Materials, Biocompatible; D055767:Immobilized Proteins; D009842:Oligopeptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C047981:arginyl-glycyl-aspartic acid
keywords: RGD peptides; endothelialization; tissue engineering; vascular endothelial growth factor; vascular graft