MORPHOGENETIC FEATURES OF REMODELING OF BIODEGRADABLE VASCULAR GRAFTS DEPENDING ON THEIR FUNCTIONAL COMPONENT

Highlight

Neointimal hyperplasia and aneurysm formation are common complications in the development of vascular grafts. For the effective assembly of newly formed tissue based on biodegradable grafts and targeted remodeling, the creation of additional incentives is an urgent issue. The study involved comparative assessment of remodeling based on biodegradable vascular grafts, depending on the presence of proangiogenic factors and the effect of an antibacterial agent on the sheep carotid artery model.

Abstract

Aim. To comparatively describe remodeling of two types of grafts, depending on the presence or absence of proangiogenic factors and the influence of an antibacterial agent.

Methods. Two types of biodegradable vascular grafts were made from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) by electrospinning. On the inner surface of the PHBV/PCL/Ilo/A vascular grafts, a drug coating was formed from cationic amphiphile and iloprost, and a reinforcing spiral frame was created by extrusion. In the manufacture of the PHBV/PCL/GFmix/Hep/Ilo vascular grafts, a composition of growth factors (GFmix) was introduced at the electrospinning stage: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and a chemoattractant molecule (SDF-1α). Additionally, iloprost and heparin were modified by complexation via polyvinylpyrrolidone to impart thromboresistant properties. The resulting grafts were implanted into the carotid artery of a sheep (n = 12). The explanted vascular grafts were examined using histological and immunofluorescence staining, the genetic profile of vascular wall remodeling was studied by quantitative polymerase chain reaction.

Results. According to the results of histological and immunofluorescence studies, a newly formed three-layer structure of vascular tissue without calcification deposits formed on the PHBV/PCL/GFmix/Hep/Ilo grafts. Genetic study showed that at 6 months of implantation, remodeling, compared to the sheep carotid artery, occurred in an inflammatory environment (IL1A, IL4, IL8), and was also characterized by inflammatory activation of the endothelium (KLF4). The newly formed vascular wall formed on the basis of the PHBV/PCL/Ilo/A grafts showed signs of neointimal hyperplasia and increased expression of anti-inflammatory IL10, which might reflect the development of a chronic inflammatory process. Moreover, it showed the formation of a vasa vasorum network in the adventitia and increased expression of the CXCR4 gene, encoding a receptor associated with angiogenesis. There were no signs of acute inflammation in both study groups, however, we detected aneurysmal expansion of vascular lumen. When comparing a newly formed vascular tissue formed on the PHBV/PCL/GFmix/Hep/Ilo grafts to a newly formed vascular tissue on the PHBV/PCL/Ilo/A grafts, we observed a lower level of expression of proinflammatory and anti-inflammatory cytokines, as well as molecules of inflammatory and prothrombotic activation of endothelial cells.

Conclusion. Growth factors introduced into the composition of the PHBV/PCL/GFmix/Hep/Ilo grafts are capable of modulating the microenvironment. After 6 months of implantation it led to the newly formed three-layer structure of vascular tissue, characterized by a decrease in the level of expression of pro- and anti-inflammatory cytokines and chemokines, as well as molecules of inflammatory and prothrombotic activation of the endothelium compared to the newly formed vascular tissue on the PHBV/PCL/Ilo/A grafts.

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