title: Bioabsorbable Bypass Grafts Biofunctionalised with RGD Have Enhanced Biophysical Properties and Endothelialisation Tested In vivo.
abstract: 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 eight and enhanced the formation of an endothelial cell monolayer in vivo 1 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.
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Antonova
authors.affiliation: Centre for Nanotechnology and Regenerative Medicine, UCL Division of Surgery and Interventional Science, University College LondonLondon, UK; NanoRegMed LtdLondon, UK.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Anton G
authors.initials: AG
authors.lastname: Kutikhin
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Sevostyanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Evgeniya O
authors.initials: EO
authors.lastname: Krivkina
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Mironov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Burago
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Velikanova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Vera G
authors.initials: VG
authors.lastname: Matveeva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Glushkova
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Evgeniya A
authors.initials: EA
authors.lastname: Sergeeva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Georgiy Y
authors.initials: GY
authors.lastname: Vasyukov
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Yuliya A
authors.initials: YA
authors.lastname: Kudryavtseva
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Barbarash
authors.affiliation: Research Institute for Complex Issues of Cardiovascular Diseases Kemerovo, Russia.
authors.forename: Leonid S
authors.initials: LS
authors.lastname: Barbarash
keywords: RGD peptides; biocompatibility; endothelialisation; morphology; physico-mechanical properties; poly(3-hydroxybutyrate-co-3-hydroxyvalerate); poly(𝜀-caprolactone); vascular grafts