title: Vascular Endothelial Growth Factor Improves Physico-Mechanical Properties and Enhances Endothelialization of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Poly(ε-caprolactone) Small-Diameter Vascular Grafts In vivo.
abstract: The combination of a natural polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a synthetic hydrophobic polymer poly(ε-caprolactone) (PCL) is promising for the preparation of biodegradable and biocompatible small-diameter vascular grafts for bypass surgery. However, physico-mechanical properties and endothelialization rate of PHBV/PCL grafts are poor. We suggested that incorporation of vascular endothelial growth factor (VEGF) into PHBV/PCL grafts may improve their physico-mechanical properties and enhance endothelialization. Here we compared morphology, physico-mechanical properties, and in vivo performance of electrospun small-diameter vascular grafts prepared from PHBV/PCL with and without VEGF. Structure of the graft surface and physico-mechanical properties were examined by scanning electron microscopy and universal testing machine, respectively. Grafts were implanted into rat abdominal aorta for 1, 3, and 6 months with the further histological, immunohistochemical, and immunofluorescence examination. PHBV/PCL grafts with and without VEGF were highly porous and consisted mostly of nanoscale and microscale fibers, respectively. Mean pore diameter and mean pore area were significantly lower in PHBV/PCL/VEGF compared to PHBV/PCL grafts (1.47 μm and 10.05 μm(2); 2.63 μm and 47.13 μm(2), respectively). Durability, elasticity, and stiffness of PHBV/PCL grafts with VEGF were more similar to internal mammary artery compared to those without, particularly 6 months postimplantation. Both qualitative examination and quantitative image analysis showed that three-fourths of PHBV/PCL grafts with VEGF were patent and had many CD31-, CD34-, and vWF-positive cells at their inner surface. However, all PHBV/PCL grafts without VEGF were occluded and had no or a few CD31-positive cells at the inner surface. Therefore, VEGF enhanced endothelialization and improved graft patency at all the time points in a rat abdominal aorta replacement model. In conclusion, PHBV/PCL grafts with VEGF have better biocompatibility and physico-mechanical properties compared to those without. Incorporation of VEGF improves graft patency and accelerates formation of endothelial cell monolayer.
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Antonova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Sevostyanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Anton G
authors.initials: AG
authors.lastname: Kutikhin
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Mironov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Evgeniya O
authors.initials: EO
authors.lastname: Krivkina
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Amin R
authors.initials: AR
authors.lastname: Shabaev
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Vera G
authors.initials: VG
authors.lastname: Matveeva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Velikanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Evgeniya A
authors.initials: EA
authors.lastname: Sergeeva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Burago
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Georgiy Y
authors.initials: GY
authors.lastname: Vasyukov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Glushkova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Yuliya A
authors.initials: YA
authors.lastname: Kudryavtseva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Barbarash
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Leonid S
authors.initials: LS
authors.lastname: Barbarash
keywords: endothelialization; morphology; patency; physico-mechanical properties; poly(3-hydroxybutyrate-co-3-hydroxyvalerate); poly(ε-caprolactone); vascular endothelial growth factor; vascular graft