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

Autor: E. A. Velikanova, Anton G. Kutikhin, Olga Barbarash, Leonid S. Barbarash, Tatiana V. Glushkova, A. V. Mironov, E. O. Krivkina, A. R. Shabaev, Georgiy Yu. Vasyukov, V. V. Sevostyanova, Larisa V. Antonova, Yuliya A. Kudryavtseva, Andrey Yu. Burago, Evgeniya A. Sergeeva, Vera G. Matveeva
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 7 (2016)
Frontiers in Pharmacology
ISSN: 1663-9812
DOI: 10.3389/fphar.2016.00230
Popis: The combination of a natural hydrophilic polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a synthetic hydrophobic polymer poly(e-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 µm2; 2.63 µm and 47.13 µm2, 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.
Databáze: OpenAIRE