BFGF and SDF-1α Improve In Vivo Performance of VEGF-Incorporating Small-Diameter Vascular Grafts.

Larisa Antonova,Vera Matveeva,Evgeniya Senokosova,Andrey Mironov,Tatiana Glushkova,Elena Velikanova,Leonid Barbarash,Amin Shabaev,Evgeniya Krivkina,Viktoriia Sevostianova,Anton Kutikhin

doi:10.3390/ph14040302

Larisa Antonova, Vera Matveeva + Show 9 more

Open Access

https://doi.org/10.3390/ph14040302

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Journal: Pharmaceuticals	Publication Date: Mar 28, 2021
Citations: 12	License type: CC BY 4.0

Affiliation: Kemerovo State University

Abstract

Tissue-engineered vascular grafts are widely tested as a promising substitute for both arterial bypass and replacement surgery. We previously demonstrated that incorporation of VEGF into electrospun tubular scaffolds from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) enhances formation of an endothelial cell monolayer. However, an overdose of VEGF can induce tumor-like vasculature; thereby, other bioactive factors are needed to support VEGF-driven endothelialization and successful recruitment of smooth muscle cells. Utilizing emulsion electrospinning, we fabricated one-layer vascular grafts with either VEGF, bFGF, or SDF-1α, and two-layer vascular grafts with VEGF incorporated into the inner layer and bFGF and SDF-1α incorporated into the outer layer with the following structural evaluation, tensile testing, and in vivo testing using a rat abdominal aorta replacement model. The latter graft prototype showed higher primary patency rate. We found that the two-layer structure improved surface topography and mechanical properties of the grafts. Further, the combination of bFGF, SDF-1α, and VEGF improved endothelialization compared with VEGF alone, while bFGF induced a rapid formation of a smooth muscle cell layer. Taken together, these findings show that the two-layer structure and incorporation of bFGF and SDF-1α into the vascular grafts in combination with VEGF provide a higher primary patency and therefore improved in vivo performance.

Highlights

Vascular tissue engineering has emerged as one of the most promising approaches for producing mechanically competent and biocompatible small-diameter vascular substitutes [1]
For the fabrication of the grafts, we used emulsion electrospinning, a well-established technique to provide a controllable and sustainable release and a synergistic delivery of bioactive agents [14,15]. This method allows chemical separation via the creation of an emulsion from: (1) an immiscible aqueous phase containing the dissolved bioactive compounds; (2) polymer solution dissolved in an organic phase, with the subsequent organization of the emulsified droplets into two distinct phases as the solvent evaporates from the electrospun fibers [16]
To properly evaluate the possible synergistic action of these bioactive factors, we developed a graft containing vascular endothelial growth factor (VEGF) incorporated into the inner layer and bFGF incorporated along with SDF-1α into the outer layer

Summary

Introduction

Vascular tissue engineering has emerged as one of the most promising approaches for producing mechanically competent and biocompatible small-diameter vascular substitutes [1]. These constructs are fabricated of natural or synthetic biodegradable polymers to provide a scaffold for cell attachment, migration, and proliferation followed by de novo formation of the vascular tissue [2]. Peptides or incorporation of vascular endothelial growth factor (VEGF) significantly and increased a primary patency rate of these grafts [5]. VEGF is frequently used to induce graft endothelialization since it promotes migration, proliferation, survival, and Pharmaceuticals 2021, 14, 302.

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