Tissue-engineered patch modified by vascular endothelial growth factor for reconstruction of vascular wall

Abstract

Background. Commercially available synthetic and animal-derived vascular patches used in patch angioplasty during carotid endarterectomy have several disadvantages, such as postoperative thrombosis or occlusion and restenosis. This problem may be resolved by the development of biologically active materials that are biodegradable and can stimulate tissue regeneration.Aim. To evaluate the properties and efficacy of a biodegradable patch based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) into which vascular endothelial growth factor (VEGF) is incorporated, in comparison with unmodified PHBV/PCL and commercial vascular patches.Methods. Porous patches were fabricated by emulsion electrospinning from a mixture of PHBV and PCL, into which VEGF was incorporated. The morphological and mechanical properties of these patches were tested, and they were implanted into the wall of rat abdominal aortas for 1, 3, 6 and 12 months. Histological and immunofluorescence examinations were performed to evaluate endothelisation, cellular composition and calcification.Results. PHBV / PCL patches with VEGF had a highly porous structure and demonstrated tensile strength similar to that of the aorta in rats and the internal thoracic artery in humans. After 3 months of implantation, an endothelial monolayer was formed on the inner surface of these patches. The patches were populated by cells that secreted the extracellular matrix faster than did cells of patches from the xenopericardium. Remodelling with PHBV / PCL patches was not accompanied by chronic inflammation; in contrast, inflammation was observed with long-term implantation of unmodified PHBV / PCL samples.Conclusion. VEGF incorporated into biodegradable PHBV / PCL patches stimulated their endothelisation, increased their biocompatibility and promoted remodelling and formation of the components of the blood vessel. PHBV / PCL / VEGF patches thus have a high potential for use in tissue engineering of the vascular wall. Received 2 June 2020. Revised 27 June 2020. Accepted 16 July 2020. Funding: This study was supported by the Complex Program of Basic Research under the Siberian Branch of the Russian Academy of Sciences within the Basic Research Topic of Research Institute for Complex Issues of Cardiovascular Diseases № 0546-2019-0002 “Pathogenetic basis for the development of cardiovascular implants from biocompatible materials using patient-oriented approach, mathematical modeling, tissue engineering, and genomic predictors”. Conflict of interest: Authors declare no conflict of interest. Author contributionsConception and study design: V.V. Sevostianova, A.V. Mironov, L.V. Antonova, R.S. Tarasov, L.S. BarbarashData collection and analysis: V.V. Sevostianova, A.V. Mironov, L.V. Antonova, E.O. Krivkina, V.G. Matveeva, E.A. Velikanova, T.V. GlushkovaStatistical analysis: V.V. Sevostianova, T.V. GlushkovaDrafting the article: V.V. Sevostianova, A.V. Mironov Critical revision of the article: L.V. Antonova, R.S. Tarasov, L.S. BarbarashFinal approval of the version to be published: V.V. Sevostianova, A.V. Mironov, L.V. Antonova, E.O. Krivkina, V.G. Matveeva, E.A. Velikanova, R.S. Tarasov, T.V. Glushkova, L.S. Barbarash