Strut Thickness and Species‐Specific Healing Are Key Considerations in Developing Zinc‐Based Biodegradable Arterial Stents

ABSTRACT Zinc‐based biodegradable stents offer a promising solution for temporary vascular support, aiding in vessel healing while reducing long‐term complications such as thrombosis and restenosis. This study examined three zinc‐based alloys: AMZ (Zn–4.0Ag–0.6Mn–0.1Zr), ACMZ (Zn–3.5Ag–0.5Cu–0.7Mn–0.1Zr), and CMM (Zn–1.0Cu–0.6Mn–0.05 Mg), all featuring reduced wire diameters of 0.12 mm. The focus was on their microstructure, mechanical performance, thrombogenicity, and in vivo biocompatibility. The alloys were processed through cold drawing and heat treatment, resulting in ultra‐fine‐grained structures measuring less than 1 μm. Energy dispersive spectroscopy (EDS) and x‐ray diffraction (XRD) analyses confirmed the presence of strengthening intermetallic phases (AgZn ₃ , CuZn ₄ , and MnZn ₁₃ ), while a uniform elemental distribution indicated solid solution strengthening. Heat treatment enhanced ductility, especially in the AMZ and ACMZ alloys, without compromising tensile strength. In vitro hemocompatibility assays showed low thrombogenicity for these alloys, with lower fibrin and FXIIa generation compared to clinical control materials. Ex vivo assessments of platelet and fibrin attachment revealed similar results to those observed with pure zinc controls. In vivo implantation of the stent materials into the abdominal aortas of mice and rats produced distinct species‐specific immune responses. Mice exhibited significant inflammation, extracellular matrix degradation, and necrosis, raising potential concerns about their biocompatibility in this model. In contrast, implants in rats resulted in only mild inflammation and limited neointimal growth, with no signs of necrosis. This suggests a more favorable and controlled healing response in rats. Morphometric analysis of Verhoeff–Van Gieson‐stained cross‐sections indicated that the 0.12 mm wires produced significantly less neointimal growth compared to previously tested 0.25 mm implants in rats, highlighting the advantages of smaller implant dimensions. Overall, these findings support the use of refined zinc‐based alloys with smaller struts for next‐generation biodegradable stents. However, the inflammatory response observed in mice emphasizes the necessity for careful selection of models in preclinical testing.