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

Abstract

Metallic stents are commonly 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. Unfortunately, iron produces a voluminous, retained oxide product in the arterial wall, whereas magnesium and its alloys corrode too rapidly. A third class of metallic bioabsorbable materials that are based on zinc has been introduced in the last few years. As summarized in this contribution, 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. They appear to be free of flaws that limit the application of iron- and magnesium-based alloys, and polymers. This review compares bioabsorbable materials and summarizes progress towards bioabsorbable stents. It emphasizes on 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.

Zn-Mg and Zn-Ag Degradation Mechanism Under Biologically Relevant Conditions

“…20 Increased hardness suggests increased strength, and alloying appears to be a possible route to reach the desired mechanical properties of a biodegradable metallic implant. 4 However, the presence of secondary phases causes selective or microgalvanic corrosion due to potential differences between the primary zinc phase and the silver-/ magnesium-rich phases. The selective corrosion mechanism may result in deterioration of mechanical properties and biocompatibility of an implant during its degradation.…”

“…13,14 However, numerous in vivo studies show thin thickness of neointimal tissue and tissue regeneration. 4, 13 Vojtech et al 11 estimated the daily release from a zinc bone screw to be 1·5 mg/d. This can be compared to the 2-3 g of zinc contained in the human body and the recommended dietary allowance of 15 mg/d.…”

“…A permanent implant may cause a late adverse effect and require a second surgery to remove the implant. 3,4 Degradable implants can reduce cost and more importantly improve the patient's quality of life by avoiding explantation surgery. 5,6 Iron and magnesium (Mg) alloys were first suggested due to their low toxicity.…”

Cardiovascular Applications of Magnesium Alloys

“…While the experimental application of coronary stents made of magnesium alloys was performed for some decades [11], degradable magnesium has hardly ever played a role in the development of other cardiovascular implants.…”

“…The treatment of cardiovascular disease often requires the implantation of prosthetic material [1][2][3][4][5][6][7] or insertion of stents [8][9][10][11][12][13][14]. The ideal cardiovascular prosthesis has good functional properties and the ability to regenerate, without activating the immune system of the host organism [15].…”