Vestnik Transplantologii i Iskusstvennyh Organov (Sep 2022)

Results of preclinical trials in a sheep model of biodegradable small-diameter vascular grafts

  • L. V. Antonova,
  • E. O. Krivkina,
  • M. Yu. Khanova,
  • E. A. Velikanova,
  • V. G. Matveeva,
  • А. V. Mironov,
  • A. R. Shabaev,
  • Е. A. Senokosova,
  • T. V. Glushkova,
  • M. Yu. Sinitsky,
  • R. А. Mukhamadiyarov,
  • L. S. Barbarash

DOI
https://doi.org/10.15825/1995-1191-2022-3-80-93
Journal volume & issue
Vol. 24, no. 3
pp. 80 – 93

Abstract

Read online

Surface modification of polymer vascular matrices is a promising development for preventing vascular graft thrombosis, improving long-term patency and accelerating remodeling. Objective: to study the outcomes of long-term patency of PHBV/PCL/GFmix grafts with iloprost (Ilo) and heparin (Hep) implanted into the carotid artery of sheep. Materials and methods. Matrices ∅4 mm were fabricated by electrospinning from a polymer composition of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) with incorporation of endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and chemoattractant molecule (SDF-1α). The fabricated matrices were then modified with Ilo and Hep by complexation via polyvinylpyrrolidone (PVP). Synthetic Gore-Tex grafts were used as a comparison group. The physical and mechanical properties of the studied matrix groups were evaluated, the surface structure of vascular grafts before and after implantation was assessed. Vascular grafts were implanted into the carotid artery of a sheep. The explanted samples were studied via histological and immunofluorescence analysis, the elemental composition of the obtained vascular graft samples was also assessed, and the gene expression profile was evaluated. Results. One day after implantation, the patency of PHBV/PCL/GFmixHep/Ilo vascular grafts was 62.5%, whereas synthetic Gore-Tex grafts had thrombosis in 100% of cases. At the same time, after 18 months of implantation, the patency of biodegradable PHBV/PCL/GFmixHep/Ilo vascular grafts decreased to 50%. Permeable drug-coated polymer grafts were completely reabsorbed after 18 months of implantation, and aneurysmally dilated newly-formed vascular tissue was formed in their place. Conclusion. Modification of the surface of PHBV/PCL/GFmix polymer grafts with Hep + Ilo coating improved long-term patency outcomes compared to synthetic Gore-Tex grafts.

Keywords