RESULTS OF PRECLINICAL STUDIES OF POLYMER PATCHES WITH PROANGIOGENIC FACTORS AND ANTI-TROMBOGENIC COATING ON A PRIMATE MODEL

Highlights

Patency of polymer patches with pro-angiogenic factors and anti-thrombogenic coating in the femoral artery of baboons reached 80% at 6 months post-implantation. No intimal hyperplasia, aneurysmal dilation, inflammation, or calcification was observed. In all patent patches, neointima formed on the luminal surface, fully lined by an endothelial monolayer; pronounced bioreabsorption of the polymer wall was absent. Thus, the patches demonstrated high functionality and biocompatibility upon long-term implantation.

Aim. To conduct preclinical trials of polymer patches with proangiogenic factors and an anti-thrombotic drug coating in a primate model, assessing their long-term patency and remodeling.

Methods. Polymer patches were fabricated using emulsion electrospinning from a polycaprolactone-polyurethane composite with a complex of proangiogenic factors. The surface of the patches featured a hydrogel coating incorporating iloprost and heparin. The polymer patches were implanted into the femoral artery of five adult male baboons for 6 months. Ultrasound examination of the femoral artery patency with the implanted patches was performed 5 days, 1, 3, and 6 months after implantation. Explanted patches and adjacent femoral artery segments were examined using stereomicroscopy and scanning electron microscopy, as well as histological and immunofluorescence studies. Statistical data processing was performed using GraphPad Prism 8.

Results. The patency rate of polymer patches at 6 months post-implantation was 80.0%. The absence of neointimal hyperplasia and aneurysmal dilation of the patch wall was confirmed. After 6 months of implantation, the polymer patches showed no significant bioresorption. In all patent patches, a neointima developed without signs of hyperplasia, which was fully covered by an endothelial monolayer along the entire length of the patch. A well-vascularized neoadventitia had formed on the outer surface of the patches.

Conclusion. At 6 months post-implantation of polymer patches with proangiogenic factors and an anti-thrombotic coating into the femoral arteries of baboons, patency rate was 80.0%. The patent patches exhibited the formation of an endothelial monolayer, neointima, and neoadventitia, with no significant resorption of the polymer wall. No signs of concomitant inflammation, calcification, or aneurysm formation were detected.

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