Biodegradable Metals for Cardiovascular Stents: from Clinical Concerns to Recent Zn-Alloys

Abstract

Metallic stents are used to promote revascularization and maintain patency of plaqued or damaged arteries following balloon angioplasty. To mitigate the long-term side effects associated with corrosion-resistant stents (i.e., chronic inflammation and late stage thrombosis), a new generation of so-called "bioabsorbable" stents is currently being developed. The bioabsorbable coronary stents will corrode and be absorbed by the artery after completing their task as vascular scaffolding. Research spanning the last two decades has focused on biodegradable polymeric, iron-based, and magnesium-based stent materials. The inherent mechanical and surface properties of metals make them more attractive stent material candidates than their polymeric counterparts. A third class of metallic bioabsorbable materials that are based on zinc has been introduced in the last few years. This new zinc-based class of materials demonstrates the potential for an absorbable metallic stent with the mechanical and biodegradation characteristics required for optimal stent performance. This review compares bioabsorbable materials and summarizes progress towards bioabsorbable stents. It emphasizes the current understanding of physiological and biological benefits of zinc and its biocompatibility. Finally, the review provides an outlook on challenges in designing zinc-based stents of optimal mechanical properties and biodegradation rate.

Keywords: biodegradable stent; cardiovascular disease; endovascular stent; zinc.

Figure 1

Pathophysiological impact of stents and possible benefits of biodegradable metallic stents (VSMC = vascular smooth muscle cell).

Figure 2

Biological roles of zinc.

Figure 3

Zn-H₂O and Zn-H₂O-X Pourbaix diagrams for physiological concentrations of X = {C, Cl, P, and S} at 37°C. Aqueous species have a light blue background, concentration-dependent regions between [Zn²⁺] = 1 μM and 1 M are white, and solid species are shown with green backgrounds. Physiological pH = 7.3 is shown by a red line. (Calculated using FactSage software.)

Figure 4

SEM image of a pure Zn wire implanted into the arterial lumen of a rat for 1 day, showing crystallization of surface and intact attached red blood cells, at this particular region of the wire.

Figure 5

SEM images of a pure Zn wire implanted into the arterial lumen of a rat for 1 – 10 days. Shown for the one day sample are wire surfaces with (bottom left) and without full coverage of a thrombus layer (top left) and close-up images of these regions (middle column – showing bare region at top and covered region at bottom). The surfaces of separate wires are shown at 3 (top right) and 10 (bottom right) days.

Figure 6

Hematoxylin and Eosin stained images from an excised zinc wire after residence in the arterial lumen for four months. White arrow in A identifies encapsulating tissue surrounding the wire, which is the region that is magnified in B. Please note that the wire cross section was originally present within the encapsulating tissue and detached during staining.

Figure 7

Materials selection plots of elongation to failure versus ultimate tensile strength. Data for conventional cast and wrought alloys from the ASM Handbook ^[150] are shown in (A). A comparable presentation is given in (B) for experimental Zn-based biodegradable metals from the following literature sources: “2011 Vojtech” ^[151a], “2015 Dambatta” ^[151b], “2015 Gong” ^[151c], “2015 Li (SR)” ^[151d], “2015 Li (M&D)” ^[151e], and “2015 Liu” ^[151f]. Red lines denote approximate mechanical benchmarks, the green shaded area denotes a region in which both requirements are satisfied, and the dashed black line shows apparent limits in strength and ductility for each group of materials. Note the difference in ultimate tensile strength (x-axis) scales.