Silk Fibroin-Based Polymer Patch with Antiproliferative Properties: Results of in vitro Tests

The aim of the study was to produce polymer patches based on a mixture of regenerated silk fibroin (SF) and thermoplastic polyurethane (PU) with sirolimus (SRL) added, and study their surface structure, physical and mechanical properties and biocompatibility in vitro. Materials and Methods. Polymer patches were produced by electrospinning from a mixture of regenerated SF and thermoplastic PU dissolved in hexafluoroisopropanol in a weight ratio of 2:1 with simultaneously added SRL at concentrations of 0.175, 0.35, 0.525, and 0.7%. We studied the patch surface ultrastructure, physico-mechanical properties, and hemocompatibility; adhesive characteristics, cytotoxicity, and the effect of Ea.hy 926 endothelial cells on the proliferation. Results. The surface of the polymer patches had a porous-fibrous structure, with isolated areas of adhesions. The maximum porosity of the patches was 45.1%. The strength and rigidity of the SF-PU-SRL 0.175 and SF-PU-SRL 0.35 patches were higher than those of native arteries; all patches were more elastic than the mammary artery. The greatest mechanical conformity to native arteries was demonstrated by the SF-PU-SRL 0.525 and SF-PU-SRL 0.7 patches. The addition of SRL decreased the hydrophilicity of the patches compared to the SF-PU matrix. Contact of blood with the surface of the SF-PU-SRL patches provoked minimal hemolysis of erythrocytes and aggregation of platelets, which confirmed the optimal hemocompatibility of the patches. The adhesion of the patch surface was 4 times lower than that of the culture plastic, without a pronounced cytotoxic effect on Ea.hy 926 endothelial cells. The patches with a SRL content of 0.525% had the optimal antiproliferative effect. Conclusion. Due to the optimal surface porosity, the greatest correspondence of rigidity, strength and elasticity to native arteries, high hemocompatibility, low cytotoxicity and the achievement of an antiproliferative effect at a minimum concentration of SRL without a negative impact on the viability of endothelial cells, the polymer patch SF-PU-SRL 0.525 seems to be the most promising that enables to proceed to the assessment of its effectiveness in terms of preventing postoperative neointimal hyperplasia and restenosis in a model of arterial wall reconstruction.