Conjugation with RGD Peptides and Incorporation of Vascular Endothelial Growth Factor Are Equally Efficient for Biofunctionalization of Tissue-Engineered Vascular Grafts

与 RGD 肽结合和血管内皮生长因子的掺入对于组织工程血管移植物的生物功能化同样有效

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作者:Larisa V Antonova, Alexander M Seifalian, Anton G Kutikhin, Victoria V Sevostyanova, Vera G Matveeva, Elena A Velikanova, Andrey V Mironov, Amin R Shabaev, Tatiana V Glushkova, Evgeniya A Senokosova, Georgiy Yu Vasyukov, Evgeniya O Krivkina, Andrey Yu Burago, Yuliya A Kudryavtseva, Olga L Barbarash,

Abstract

The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine-glycine-aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31⁺/CD34⁺/vWF⁺ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31⁺CD34-vWF⁺ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31⁺/CD34⁺ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.

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