Abstract

Background Currently, the search for the bioactive molecules capable of promoting formation of the vascular tissue is still ongoing. We have previously demonstrated that incorporation of the growth factors and chemoattractant molecules into the biodegradable tubular scaffolds can increase their primary patency upon the implantation into rat abdominal aorta. However, further studies are required to investigate tissue remodeling using functionalized vascular grafts with the same diameter as a replaced native vessel. Aim To investigate the specific aspects of de novo vascular tissue formation and calcification employing rat abdominal aorta interposition model and vascular grafts with 1.5 mm diameter with incorporated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor (SDF)-1α. Methods Tubular grafts with a diameter of 1.5 mm were blended of poly(3-hydroxybutyrateco-3-hydroxyvalerate) and poly(ε-caprolactone) (PHBV/PCL). Grafts without growth factors were fabricated using standard electrospinning technique whilst grafts with incorporated growth factors were prepared utilizing emulsion electrospinning. VEGF was incorporated into the inner third, whereas bFGF and SDF-1α were incorporated into the outer two-thirds of the graft. Grafts were implanted into the abdominal aortas of Wistar rats for 1, 3, 6, and 12 months following scanning electron microscopy along with histological and immunofluorescent examination. Results Primary patency of the grafts with VEGF, bFGF, and SDF-1α reached 93% indicative of structural integrity of the vascular tissue. Neither signs of inflammation nor severe calcification was detected. Conclusion As in 2 mm diameter vascular grafts, incorporation of bioactive factors into 1.5 mm diameter grafts increased their long-term primary patency and improved vascular tissue formation in comparison with non-modified grafts.

Highlights

  • IntroductionPotential benefits of the layered incorporation of several growth factors and chemoattractant molecules into the scaffold and their influence on the cells have been shown [4]

  • We have previously demonstrated that incorporation of the growth factors and chemoattractant molecules into the biodegradable tubular scaffolds can increase their primary patency upon the implantation into rat abdominal aorta

  • vascular endothelial growth factor (VEGF) was incorporated into the inner third, whereas basic fibroblast growth factor (bFGF) and stromal cell-derived factor (SDF)-1α were incorporated into the outer two-thirds of the graft

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Summary

Introduction

Potential benefits of the layered incorporation of several growth factors and chemoattractant molecules into the scaffold and their influence on the cells have been shown [4]. The incorporation of vascular endothelial growth factor (VEGF) into the inner third, and the basic fibroblast growth factor (bFGF) and chemoattractant molecule SDF-1a into the outer 2/3 of the graft wall may stimulate the formation of the endothelial and smooth muscle layers and enhance 100% patency noted at 12 months after their implantation into the vascular bed of small laboratory animals. The small number of the implanted grafts in the previous experiments (n = 4), the mismatch between the diameters of the rat aorta (ø 1.2 mm) and the graft itself (ø 2.0 mm) point specific gaps in evidence and set challenges for vascular tissue remodeling using biodegradable scaffolds with improved morphology of the internal surface that we addressed in the current study

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