Zein nanospheres assisting inorganic and organic drug combination to overcome stent implantation-induced thrombosis and infection

Abstract

The complication of stent implantation is the biggest obstacle to the success of its clinical application. In this study, we developed a combination way of 3D printing and the coating technique for preparation of functional polyurethane stents against stent implantation-induced thrombosis and postoperative infection. SEM, XPS, static water contact angle, and XRD demonstrated that the functional polyurethane stent had a 37 μm-thickness membrane composed of zein nanospheres (250-350 nm). Meanwhile, ZnO nanoparticles were encapsulated in zein nanospheres while heparin was adsorbed on the surface, causing 97.1 ± 6.4 % release of heparin in 120 min (first-order kinetic model) and 62.7 ± 5.6 % release of Zn²⁺ in 9 days (Korsmeyer-Peppas model). The mechanical analysis revealed that the functional polyurethane stents had about 8.61 MPa and 2.5 MPa tensile strength and bending strength, respectively. The in vitro biological analysis showed that the functional polyurethane stents had good EA.hy926 cells compatibility (97.9 ± 3.8 %), anti-coagulation response (comparable plasma protein, platelet adhesion and suppressed clotting) and sustained antibacterial activities by comparison with the bare polyurethane stent. The preliminary evaluation by rabbit ex vivo carotid artery intervention experiment demonstrated that the functional polyurethane stents could maintain blood circulation under the continuous stresses of blood flow. Meanwhile, the detailed data from the simulated implant infection experiment in vivo showed the functional polyurethane stents could effectively reduce microbial infection by 3-6 times lower and improve fibrosis and macrophage infiltration.

Keywords: 3D printing; Functional polyurethane stent; Postoperative infection; Thrombosis; Zein.