Poly-D,L-Lactide-co-Glycolide and Sodium Enoxaparin Composition - an Advanced Coating for Vascular Stents: Biocompatibility and Efficiency Assessment of Stent-Grafts in an Experiment on Large Animals.

Materials and Methods: A biodegradable coating based on a copolymer of poly-D,L-lactide-co-glycolide (the polylactide-glycolide ratio - 50:50) and low-molecular sodium enoxaparin was applied on 8-mm-long metallic coronary Calipso stents by electrospinning. The sheep carotid artery was implanted with the coated stents (stent-grafts) and uncoated stents. The dynamic patency was assessed by color duplex ultrasound. Three months later, the artery-stent fragments were explanted, fixed with buffered formalin with post-fixation with osmium tetroxide, dehydrated in ethanol and acetone followed by impregnating with epoxy resin. After polymerization, the samples were ground and polished to the required depth. To enhance the contrast after polishing, the samples were treated with Reynolds lead citrate. The samples were visualized by scanning electron microscopy in the backscattered electron mode. Results: During the three-month experiment, no cases of thrombosis or stenosis of stents and stent-grafts were revealed. A uniform dense neointima up to 165 μm thick formed on the internal surface of the stent-grafts, it was twice as thick as the intima of the intact carotid artery adjacent to the stent-graft. A loose neointima formed on the inner part of the stents without a polymer membrane, reaching 380 μm in some places. All samples demonstrated a classic picture of the formation of a dense fibrous capsule, which separated the metal stent struts from the blood flow and structural elements of the artery, however, the morphology and cellular composition in the samples varied significantly. The struts of the stents without a membrane were surrounded by numerous inflammatory cells. The environment of the stent grafts was represented mainly by smooth muscle cells, fibrocytes, fragments of the elastic membrane located in the intercellular matrix; there were no inflammatory cells. The polymer coating of the stent-grafts completely degraded forming no scar tissue. Conclusion: The developed polymer coating based on a copolymer of poly-D,L-lactide-co-glycolide (the polylactide-glycolide ratio - 50:50) and the low-molecular sodium enoxaparin for a vascular stent appeared to be effective. When implanted in sheep carotid arteries, the stent-grafts cause no development of thrombosis and stenosis, successfully integrating with the animal artery. In 3 months, complete resorption of the polymer coating occurred with no signs of a chronic inflammatory reaction.