Biodegradable vascular graft modified by RGD-peptides: experimental research

Research goals. To study the effectiveness of RGD-peptide modification of the small-diameter biodegradable vascular grafts depending on the type of a linker and RGD configuration.Material and Methods. Tubular scaffolds with a diameter of 1.5 and 4.0 mm were produced by electrospinning from polyhydroxybutyrate/valerate (PHBV) and polycaprolactone (PCL). The PHBV/PCL grafts were modified with RGD peptides. In vitro experiments showed the degree of erythrocyte hemolysis and adhesion of the platelets and endothelial cells when in contact with a modified surface. The physico-mechanical properties and the structure of graft surface were studied before and after modification. The PHBV/PCL and PHBV/PCL/RGD vascular grafts were implanted into the abdominal aorta of rats for the periods of 1 and 3 months. Explant samples were studied using confocal microscopy and histological methods.Results. The results of physical and mechanical tests showed a significant decrease in the strength properties of the PHBV/PCL/RGD grafts relative to the unmodified analogs. A significant increase in platelet aggregation was found in the modified grafts. The level of adhesion of the endothelial cells on the modified surfaces was higher than that on the unmodified surfaces. Shortterm implantation of the grafts for 1 and 3 months showed that the modified grafts had higher patency and a less tendency to calcification compared with the unmodified grafts. Immunofluorescence study demonstrated the significant superiority of the modified vascular grafts in terms of stimulating the formation of a mature endothelial monolayer. A longer linker of 4,7,10-trioxa-1,13-tridecane diamine was found to increase the bioavailability of RGD peptides; the use of RGDK and c[RGDFK] for surface modification of the grafts stimulated early endothelialization of the internal surface of the implants and reduced the prosthetic wall calcification tendency, which together increased the patency of the implanted grafts.Conclusion. In short-term implantation of biodegradable vascular grafts modified with RGD peptides, the grafts with RGDK and c[RGDFK], attached to the surface of the prostheses through the 4,7,10-triox-1,13-tridecane diamine linker, showed the best results in terms of endothelial adhesion and maintenance of the viability of the endothelial cells in vitro and endothelialization in vivo; these grafts had high patency after implantation into the bloodstream of small laboratory animals and a less tendency to calcification.