Biodegradable Metal Stent Alloys for Vascular Applications

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PROJECT SUMMARY Cardiovascular disease remains the leading cause of morbidity and mortality in the US, despite decades of advancements in treatment, including stent coatings and anti-platelet therapies. The improvements in stent material technology progressed from bare metal stainless steel, cobalt-chromium, and nitinol (high thrombogenicity and high restenosis) to drug eluting polymer coated metals (lowered restenosis, but thrombogenic) to biodegradable polymers (potential to decrease restenosis, but still thrombogenic). Despite these incremental advances, thrombosis and in-stent restenosis all remain significant clinical obstacles, limiting the life-saving potential of stent applications in cardiac and peripheral arteries and requiring life-long prescription of anticoagulant and antiplatelet therapies for patients. Recently, biodegradable metals have garnered interest for stent applications to reduce thrombosis and restenosis. Biodegradable metal vascular stents must have sufficient mechanical strength to maintain an open lumen for at least 6 months, must be non-thrombogenic, prevent restenosis, and degrade between 6 months and 2 years, while maintaining cytocompatibility. Biodegradable metal stents bioresorb through corrosion by which the metal is converted to a more stable form, such as its oxide, hydroxide or sulphide state. Initial studies of biodegradable metals like iron (Fe), magnesium (Mg), and zinc (Zn) have shown promise in terms of mechanical properties and degradation rates. Importantly, the degradation products of these metals are biocompatible ions which contribute to cell functions. A single metal does not meet the requirements of a biodegradable metallic stent, yet metallic alloys and optimization of materials processing techniques can satisfy the stringent requirements. We have established the ability to design, manufacture, and test alloys with up to 5 metal alloying elements based on zinc and magnesium. Through our proposed work, the impact of critical processing steps (e.g., hot extrusion, cold drawing) on material properties, particularly microstructure, biodegradation rate, and biodegradation uniformity, will be determined. We will quantify the biological responses of pure and alloyed biodegradable metals to determine their performance in the vascular system, particularly emphasizing thrombosis, restenosis, and inflammatory responses to the alloyed metals and their degraded ions. In the present proposal, our goal is to develop biodegradable metal alloys that meet the strict mechanical and biologic requirements of vascular stents. The overall objective of this project is to identify alloying elements and material processing requirements for biodegradable metal materials that can suppress local thrombo-inflammatory responses by (1) developing and characterizing the mechanical, material, and surface properties of biodegradable metal alloys and (2) establishing the biocompatibility of biodegradable metals for vascular stent applications. Successful completion of this R01 will result in identification of biodegradable metal alloys that meet the mechanical and biological requirements of vascular stents, and set the stage for long-term pre-clinical testing.