Bioabsorbable bypass grafts biofunctionalised with RGD have enhanced biophysical properties and endothelialisation tested in vivo

Autor: Larisa V Antonova, Anton G. Kutikhin, Alexander Marcus Seifalian, Victoria V Sevostyanova, Evgeniya O Krivkina, Andrey V Mironov, Andrey Yu Burago, Elena A Velikanova, Vera G Matveeva, Tatiana V Glushkova, Evgeniya A Sergeeva, Georgiy Yu Vasyukov, Yuliya A Kudryavtseva, Olga L Barbarash, Leonid S Barbarash
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 7 (2016)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2016.00136
Popis: Small diameter arterial bypass grafts are considered as unmet clinical need since the current grafts have poor patency of 25% within 5 years. We have developed a 3D scaffold manufactured from natural and synthetic biodegradable polymers, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL), respectively. Further to improve the biophysical properties as well as endothelialisation, the grafts were covalently conjugated with arginine-glycine-aspartic acid (RGD) bioactive peptides. The biophysical properties as well as endothelialisation of PHBV/PCL and PCL 2 mm diameter bypass grafts were assessed with and without biofunctionalisation with RGD peptides in vitro and in vivo. Morphology of the grafts was assessed by scanning electron microscopy, whereas physico-mechanical properties were evaluated using a physiological circulating system equipped with a state of art ultrasound vascular wall tracking system. Endothelialisation of the grafts in vitro and in vivo were assessed using a cell viability assay and rat abdominal aorta replacement model, respectively. The biofunctionalisation with RGD bioactive peptides decreased mean fiber diameter and mean pore area in PHBV/PCL grafts; however, this was not the case for PCL grafts. Both PHBV/PCL and PCL grafts with RGD peptides had lower durability compared to those without; these durability values were similar to those of internal mammary artery. Modification of PHBV/PCL and PCL grafts with RGD peptides increased endothelial cell viability in vitro by a factor of 8 and enhanced the formation of an endothelial cell monolayer in vivo one month postimplantation. In conclusion, PHBV/PCL small-caliber graft can be a suitable 3D scaffold for the development of a tissue engineering arterial bypass graft.
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