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.

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

“…We previously found that either conjugation with RGD peptides or incorporation of VEGF improve biophysical properties of electrospun PHBV/PCL small-diameter vascular grafts [22,23]. Modification with VEGF reduced mean pore area and mean fiber diameter in comparison with modification with RGD peptides [22,23].…”

“…Modification with VEGF reduced mean pore area and mean fiber diameter in comparison with modification with RGD peptides [22,23]. Grafts with incorporated VEGF consisted mostly of nanofibers; on the contrary, those with RGD were formed mostly of microfibers [22,23].…”

“…The following studies by our group demonstrated that either conjugation with RGD peptides or the incorporation of VEGF improves biocompatibility, physico-mechanical properties, and enhances endothelialization of electrospun PHBV/PCL vascular grafts [22,23]. However, in vivo comparative assessment of the mentioned modifications in either short- or long-term periods is still lacking.…”

Biological Analogs of Infrainguinal Arteries: Evolution and Development Prospects (Review)

“…And due to this fact the qualityprice ratio of most tissue engineering products are likely to exceed the threshold of availability. However, some developments have been started, and it is hoped that with time researchers will overcome the difficulties [112,113].…”

Modification by RGD-Peptides of Vascular Grafts of Small Diameter From Polyparolactone: Experimental Study Results

“…Ранее мы показали успешность конъюгирова-ния RGD-пептидов с поверхностью графтов на основе поликапролактона (poly(ɛ-caprolactone), PCL) через карбодиимид, который известен как метод химического перекрестного связывания нулевой длины [5]. Кроме того, в эксперименте in vitro доказано положительное влияние RGD-мо-дификации на клеточную интеграцию [6].…”