Composite Tissue-Engineered Small-Diameter Vascular Grafts Based on Polycaprolactone and Polyurethane with Growth Factors and Atrombogenic Drug Coatings: Surface Ultrastructure, Physical and Mechanical Properties.

Abstract

There is a growing need for synthetic small-diameter vascular grafts (<6 mm) for bypass surgery since the majority of currently developed products have demonstrated unacceptable high frequency of thrombosis in preclinical studies. The proprietary composite vascular graft based on a nonwoven polymer with anti-thrombogenic and anti-aneurysm effect and functional activity is aimed at stimulating the formation of vascular neotissue at the implantation site. The aim of the investigation is to study the surface morphology, physical and mechanical properties of the polycaprolactone/ polyurethane (PCL/PU) small-diameter tissue-engineered vascular graft with growth factors and an anti-thrombogenic surface coating.

Materials and methods: PCL/PU vascular grafts with growth factor mix (GFmix) were manufactured using the electrospinning method. The hydrogel coating containing iloprost (Ilo) and heparin (Hep) was formed by complexation with polyvinylpyrrolidone. The controls were multilayer vascular grafts of similar composition and nonwoven matrices based on 12% PCL and 12% PU. The surface structure was analyzed with the S-3400N scanning electron microscope (Hitachi, Japan). The physical properties of the surface were determined by the wetting angle method. The mechanical properties were evaluated on a Z series universal testing machine (Zwick/ Roell, Germany). Statistical processing of the data was performed using the GraphPad Prism 8 software.

Results: Our new manufacturing technique for the composite PU/PCL/GFmix/^Ilo/Hep graft has eliminated the problem of graft delamination. The inner surface of the graft consisted of interwined microfibers (1.34 [1.15; 2.28] μm thick), nanofibers (790.0 [604.0; 853.5] nm thick), and interpenetrating pores of different diameters (5.4 [3.8; 8.4] μm). The process of coating formation did not affect the fibers and did not seal the pores, the surface retained its hydrophilic properties (θ=68.61±11.85°). The tensile strength (3.45 [3.17; 4.03] MPa) and Young's modulus (4.88 [3.95; 5.80] MPa) of PU/PCL/GFmix/^Ilo/Hep grafts were almost similar to the human internal thoracic artery compared to the multilayer analogs. The PU/PCL/GFmix/^Ilo/Hep grafts were superior to the multilayer PCL/PU/GFmix/^Ilo/Hep grafts in terms of reduced excessive elasticity (to 118.0 [111.0; 125.0]%; p=0.043).

Conclusion: The composite functionalized vascular PU/PCL/GFmix/^Ilo/Hep grafts have enhanced characteristics and compliance, which, in turn, increases the probability of their high patency in future preclinical studies.