RESULTS OF PRECLINICAL TESTS OF SMALL-DIAMETER TISSUE ENGINEERED VASCULAR GRAFTS ON THE PRIMATE MODEL

Highlights

Following the development of an effective small-diameter tissue engineered vascular grafts, we have conducted preclinical tests of the new product on a primate model. 6 months after implantation, the patency of vascular grafts was 83.3%, there were no signs of aneurysm formation and pronounced inflammation. Remodeling of vascular grafts was accompanied by the formation of a neointima lined with endothelium and neoadventitia, whereas the integrity of the polymer frame remained high.

Annotation

Aim. To conduct preclinical tests of the small-diameter tissue engineered vascular grafts on a primate model with subsequent assessment of patency and remodeling.

Methods. We created vascular grafts using a polymer composition of polycaprolactone and polyurethane with proangiogenic factors by emulsion electrospinning. On the inner surface, we formed a hydrogel coating consisting of iloprost and heparin. The obtained grafts were implanted into the femoral artery of adult male baboons for 6 months. After 5 days, 1, 3 and 6 months of implantation we performed ultrasound examination to assess patency. Moreover, we performed stereomicroscopy, scanning immunofluorescence staining of explanted samples. Statistical data processing was carried out using the GraphPad Prism 8 software.

Results. The patency of vascular grafts after 6 months of implantation was 83.3%. The examinations of the samples confirmed the absence of aneurysms and stenoses during the entire follow-up period. Upon inspection, we noted that the explanted grafts were surrounded by a thin vascularized connective tissue capsule. 6 months after implantation, the polymer scaffolds of the grafts did not have pronounced bioresorption. We observed a neointima with a thickness of 192.9 (138.4; 258.1) microns, a neoadventitia with a thickness of 233.2 (188.1; 510.4) microns and a continuous endothelial monolayer on the lumen side in all patent grafts.

Conclusion. The grafts retained patency in 83.3% of cases 6 months after implantation into the femoral arteries of baboons. Moreover, all patent grafts showed the formation of neointima and neoadventitia with a functionally active endothelial monolayer. There were no signs of concomitant inflammation, calcification or aneurysms.

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