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Biomaterials

Biomaterials - Poster Session E

Poster C4 - Thrombogenicity of zinc alloys for vascular stent applications

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Bioresorbable stents are devices designed to keep arterial passageways open while degrading completely into products that can be processed by the body. Lasting approximately 2 years in the vessel, these stents reduce long-term complications such as restenosis and late-stage thrombosis and simplify future treatment options.1 Materials such as PLLA, a biodegradable polymer, and metals, including magnesium and iron have been studied for their corrosion behavior. Of these materials, zinc (Zn)-based stents have been highlighted for their favorable degradation patterns and compatibility with vessel healing.2 Specifically, the galvanic corrosion potential of pure zinc lies between magnesium and iron at −0.76V, resulting in a degradation rate of ~0.02 mm/year in vivo.1,2 Due to its poor mechanical strength, pure Zn is unsuitable for stent applications; therefore, alloying is used to improve the mechanical characteristics while maintaining its biocompatibility. However, the hemocompatibility of these alloys is needed to ensure their aptitude for clinical usage. In this study, the thrombogenicity of pure Zn, three Zn alloys, and clinical standards [cobalt chromium (CoCr) and nickel titanium (NiTi)] are compared using in vitro characterizations of the contact and common pathways of coagulation.

Materials and

Methods:  Zn alloy wires (diameter = 0.125 mm) were obtained from Fort Wayne Metals: CMM (Zn-1.0Cu-0.6Mn-0.05Mg), AMZ (Zn-4.0Ag-0.6Mn-0.1Zr), and ACMZ (Zn-3.5Ag-0.5Cu-0.7Mn-0.1Zr). Pure Zn wires (diameters = 0.25 mm for Zn-0.25 and 0.125 mm for Zn-0.125) were obtained from Goodfellow, Inc. CoCr (Goodfellow, Inc; Co40-Cr20-Fe15-Ni15-Mo7-Mn2-C-Be, d = 0.25 mm) and NiTi (Goodfellow, Inc; Ni55-Ti45, d = 0.25 mm) were used as biostable clinical controls. Wires were cut into 6 mm lengths and incubated with pooled platelet poor plasma (PPP) from 6 donors (3 male, 3 female). The amount of FXIIa, the initiator of the contact pathway, and the time to fibrin generation, the endpoint of the common coagulation pathway, were assessed through in vitro testing (n = 12 for each assay). The activation of FXII into FXIIa was measured using the chromogenic substrate S-2302, in which the rate of substrate cleavage is proportional to the amount of FXIIa generated. To characterize the generation of fibrin, 25 mM CaCl2 was added to each well to activate the coagulation cascade and the time elapsed before clotting was measured through a change in turbidity.

Results, Conclusions, and Discussions: In this study, the diameter of pure Zn wires did not significantly affect the FXIIa or fibrin generation, as Zn-0.25 and Zn-0.125 generated equivalent amounts of FXIIa with equivalent times to fibrin generation (Figures 1 and 2); therefore, the Zn alloys were compared to the biostable wires. All wire samples showed a significantly greater thrombogenic effect compared to the plasma control for both FXIIa and fibrin generation. Pure Zinc showed significantly lower FXIIa generation than NiTi. FXIIa and fibrin generation of CoCr did not differ significantly from pure Zn. Among the Zn alloy wires, CMM, ACMZ, and AMZ caused significantly less FXIIa generation than NiTi. Furthermore, CMM and ACMZ both had significantly longer clotting times than NiTi. The effect of Zn alloying on thrombogenicity did not differ significantly between alloys for either FXIIa or fibrin generation.
The results of this study indicate that alloying Zn does not significantly affect the thrombogenicity when compared to pure Zn. AMZ was the only alloy to generate significantly less FXIIa than pure Zn. This difference could be a result of the alloying materials, as AMZ is the only of the alloys in this study to contain no copper (Cu). Processing the wires could also result in a difference in the grain sizes of each wire and affect the surface interaction with plasma.

Furthermore, Zn alloys also had decreased FXIIa generation and delayed time to fibrin generation compared to a NiTi clinical control, signifying increased hemocompatibility of Zn-based bioresorbable stents in comparison to current biostable NiTi stents.  

These findings suggest that alloying Zn does not negatively affect its hemocompatibility within the coagulation cascade. This opens possibilities for alloying to optimize tensile strength and ductility for cardiovascular stent applications. Future work will include assessment of platelet activation and whole blood responses to bioresorbable Zn alloys to characterize the hemocompatibility of alloyed Zn stents.

Acknowledgements (Optional):  References
1 P.K. Bowen, et al. (2016) Adv Healthc Mater 5(10):1121-1140
2 E. Mostaed, et al. (2018) Acta Biomater 71:1-23.