Developments in metallic biodegradable stents

doi:10.1016/j.actbio.2009.10.006

Acta Biomaterialia

Volume 6, Issue 5, May 2010, Pages 1693-1697

https://doi.org/10.1016/j.actbio.2009.10.006 Get rights and content

Abstract

Interest in metallic degradable biomaterials research has been growing in the last decade. Both scientific journals and patent databases record a high increase in publications in this area. Biomedical implants with temporary function, such as coronary stents, are the targeted applications for this novel class of biomaterials. It is expected that stents made of degradable biomaterials, named biodegradable stents, will provide a temporary opening into a narrowed arterial vessel until the vessel remodels and will progressively disappear thereafter. Biodegradable stents made of metal have recently been progressed into preclinical tests in humans after their first introduction in early 2000s. By referring to patents and journal publications, this paper reviews the developments in biodegradable stents, with emphasis on those made of metals, starting from the first design ideas to validation testing.

Introduction

In recent years, the study of degradable biomaterials has become one of the most revolutionary research topics at the forefront of biomaterials. Over the last decade, a large increase in publications on metallic degradable biomaterials research has been recorded in both scientific journals and patent databases. This novel class of biomaterials is expected to be used for implants with a temporary function, such as coronary stents. Stents made of degradable biomaterials, named biodegradable stents, is a novel technological approach in accordance with the new understanding of clinical events in the arterial wall during and after stent implantation. It is expected to provide a temporary opening to a narrowed arterial vessel until the vessel remodels, and to disappear progressively thereafter. This might be providential, for example, in treating congenital heart disease in growing babies.

Biodegradable stents have not yet entered clinical practice, but results from early studies have shown their feasibility [1], [2] and generated great expectation for clinicians, patients, industrialists and researchers. The most recent clinical advances were devoted to the use of biodegradable stents made of magnesium alloy to treat two cases of congenital heart disease in babies [3], [4] and to treat critical limb ischaemia (CLI) cases in adults [5], [6]. Furthermore, a non-randomized multi-centre clinical trial of Mg stents for treating coronary arteries in adults was recently conducted [7]. The results seemed encouraging, even though further improvement, mainly to the materials, was suggested.

This paper aims to review the last 10 years of developments in biodegradable stents, with emphasis on those made of metals, and to provide a picture of recent achievements, current challenges and future advancements.

Section snippets

Idea of biodegradable stents

Basically, a stent provides a mechanical opening support and prevents early recoil to the arterial vessel [8], [9]. However, it is often claimed that the role of stenting is temporary, mainly because remodelling of the arterial wall is expected as a consequence of the mechanical stresses generated by the deployed stent [10]. The continued presence of the stent becomes unnecessary as the arterial tissue finds a new equilibrium after having been stressed by deployment of the stent. From a

Development

A biodegradable stent can be incorporated with an anti-restenotic drug, leading to an ideal structure of drug-eluting biodegradable stent [19]. Basically, it will consist of a stent backbone coated with a drug-eluting layer. This structure has been described in several patents, including one that claimed a degradable metal stent with an agent-containing layer [20] and a bioresorbable metal stent with a biodegradable coating [21]. The backbone normally consists of solid struts, but a recent

In vitro and in vivo degradation studies

In vitro studies were conducted to investigate degradation behaviour and to assess early signs of cell compatibility of the alloys, i.e., cell viability. Immersion (ASTM G31) [54] and electrochemical (ASTM G59 and ASTM F 2129) [55], [56] tests are two common methods used for degradation studies. In addition, a dynamic immersion test was used to simulate conditions in the human coronary artery, showing the important role of shear stress on degradation behaviour [33]. Meanwhile, the ISO

Concluding remarks

The last decade has witnessed increasing research interest in the forefront of the biomaterials field: biodegradable implants. The introduction of biodegradable implants, especially those made of metals, is breaking the established paradigm in which metallic biomaterials must be “corrosion-resistant”, which has been stated and explained in textbooks and investigated in a number of scientific papers for more than half century. First introduced in 2001, stents made of biodegradable metals have

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Cited by (523)

Mechanical and corrosion properties of biodegradable magnesium mini-tubes with different grain morphologies: Size and distribution
2024, Journal of Materials Science and Technology
Biodegradable magnesium (Mg) alloys have received much attention due to their biocompatibility and biodegradation. In this study, to uncover the effects of grain morphologies, including grain size and distribution on mechanical and corrosion properties, biodegradable Mg-2.1Nd-0.2Zn-0.5Zr (wt.%) (denoted as JDBM) alloy mini-tubes for stent application with three typical microstructures were achieved successfully by adjusting drawing parameters. Samples with the bimodal structure exhibit the highest strength-ductility balance attributed to the combined effects of fine grains and coarse grains, but show the fastest corrosion rate of about 1.00 ± 0.136 mm/year mainly due to the formation of micro galvanic couples between coarse and fined grains. Samples with fine equiaxed grains show the lowest corrosion rate of about 0.17 ± 0.059 mm/year, as well as uniform corrosion mode and mechanical properties of yield strength (YS) 256 ± 5.7 MPa, ultimate tensile strength (UTS) 266 ± 3.8 MPa, and elongation to failure (EL) 13.5% ± 1.8%, attributed to the high-density grain boundaries. Samples with coarse equiaxed grains exhibit medium corrosion resistance and mechanical properties of about 175 ± 4.8 MPa, 221 ± 4.0 MPa, and 21.53% ± 4.1%. Considering the mechanical and in vitro corrosion properties, biodegradable JDBM alloy implants are recommended to be composed of fine equiaxed grains, which can be used as microstructural targets for fabrication and processing.
Microstructure, wear resistance, corrosion behavior, and cytotoxicity of Mg-Zn-Ca amorphous coatings fabricated by laser surface melting
2024, Surfaces and Interfaces
To address the issues of rapid degradation rate in biodegradable magnesium alloys, which seriously restricts their clinical application, this study employed laser surface melting (LSM) on Mg-Zn-Ca alloys. The impact of the LSM process on the microstructural characteristics of magnesium alloy was examined. Subsequently, an assessment was conducted to analyze the hardness, corrosion resistance, friction and wear properties, as well as cytotoxicity of amorphous coatings applied on magnesium alloy for potential use in biodegradable implants. When the laser scanning power was set at 500 W and scanning speed was adjusted to 90 mm/s, the LSM alloy exhibited good comprehensive of properties, with a microhardness of 540 HV and a friction coefficient of 0.2024. Electrochemical analysis conducted in simulated body fluid (SBF) solution revealed that the LSM sample demonstrated favorable resistance to corrosion, as evidenced by a corrosion potential of -1.3346 V, corrosion current density of 0.0199 mA/cm², and corrosion rate of 0.455 mm/y. Both the cast and LSM alloys exhibited non-toxicity towards SaOS2 cells, with the LSM alloys displaying slightly superior biocompatibility than the as-cast alloys.
Unveiling the microstructure evolution and deformation mechanisms of micro-alloying Mg-1.5Zn-0.5Zr-0.5Sr alloy via extrusion-shearing
2024, Journal of Materials Research and Technology
Obtaining high strength without sacrificing ductility in Mg alloys is of great importance. However, the hexagonal close-packed crystal structure critically limits the deformation of Mg alloys. In this work, novel Mg-1.5Zn-0.5Zr-0.5Sr (wt.%) alloys were fabricated through homogenization, direct extrusion (DE), and extrusion-shearing (ES) processes. The effects of three different processes on microstructures, texture, and mechanical properties were thoroughly investigated. The results show that the average grain size of the alloy was greatly refined after hot extrusion. The alloy after the DE process exhibited a typical bimodal microstructure with dynamic recrystallized (DRXed) grains showing a strong < $10 \overline{1} 0$ > fiber texture parallel to extrusion direction (ED), while the small-sized unDRXed grains showed relatively weak basal texture. In addition, the strength was significantly improved, with the value of yield strength (YS) reaching ∼229 MPa and ultimate tensile strength (UTS) reaching ∼262 MPa. This is mainly attributed to grain boundary strengthening and dislocation strengthening. Compared to the DE-processed alloy, the basal texture intensity was significantly decreased and non-basal slip was activated after the ES process, which indicates that the shearing deformation during ES could improve the ductility, with the fracture elongation (FE) increased from ∼13.9 % to ∼21.4 %. This work aims to unveil the deformation mechanisms in Mg-1.5Zn-0.5Zr-0.5Sr alloy and provides an efficient way for preparing micro-alloying Mg alloys with low cost and significant improvement of comprehensive properties.
A self-healing coating with embedding of polyphenols on magnesium: Towards enhanced corrosion protection for biodegradable vascular implants
2024, Chemical Engineering Journal
Biodegradable magnesium-based vascular stent has become a research hotspot in the field of interventional medical engineering. However, the rapid degradation rate and inadequate biocompatibility of magnesium-based vascular stents often lead to implant failure in biomedical applications. It is of great research significance to slow down the degradation rate of magnesium-based stents and impart them with multifunctional bioactivity through surface modification. In this study, a self-healing coating with embedding of polyphenols is developed to create on the surface of magnesium towards corrosion protection and biocompatibility. By controlling and studying the self-healing responsiveness of the coating, the corrosion resistance under vascular implantation conditions is investigated. The embedding of polyphenols endows the interface a self-healing capability, which might be drawn as the chelation between phenol/metal ions and the formation of intermolecular connection between each of the chelating units which ultimately cause enhanced corrosion protection. Furthermore, the evaluation of biocompatibility indicates that the polyphenol-loaded polymer layer shows good biocompatibility, which is beneficial for the repair of the vascular microenvironment. These results suggest significant potential applications of this composite coating in magnesium-based vascular stents.
Enhanced in-vitro degradation resistance and cytocompatibility of a thermomechanically processed novel Mg alloy: Insights into the role of microstructural attributes
2024, Journal of Magnesium and Alloys
The role of microstructural features on in-vitro degradation and surface film development of a thermomechanically processed Mg-4Zn-0.5Ca-0.8Mn alloy has been investigated employing electrochemical studies, scanning electron microscopy and X-ray photoelectron spectroscopy. The specimen forged at 523 K temperature developed a coarse unimodal microstructure consisting of basal oriented grains, whereas the specimens forged at 623 K and 723 K temperatures exhibited bimodal microstructures containing randomly oriented fine grains and basal oriented coarse grains. The bimodal microstructures exerted higher resistance to corrosion compared to the unimodal microstructure in presence of a protective surface film. The optimum size distribution of fine and coarse grains as well as the prevalence of basal oriented grains led to the lowest anodic current density in the specimen forged at 623 K. The morphology of Ca₂Mg₆Zn₃ precipitates governed the cathodic kinetics by controlling the anode to cathode surface area ratio. Despite the specimen forged at 723 K comprised comparatively lower fraction of precipitates than at 623 K, the mesh-like precipitate morphology increased the effective cathodic surface area, leading to enhanced localised corrosion in the former specimen. Optimal microstructural features developed at 623 K forging temperature formed a well-protective surface film with lower Mg(OH)₂ to MgO ratio, exhibiting distinctly high polarization resistance and superior cytocompatibility in terms of cell-proliferation and cell-differentiation.
Corrosion inhibition induced by captopril in Hanks’ solution on bioresorbable Mg–Zn-(Y, Nd) alloys fabricated by powder metallurgical technology
2024, Materials Chemistry and Physics
Mg–Zn alloys containing rare-earth elements (REEs) have been regarded as potential candidates for bioresorbable stent materials. As implanted in coronary arteries, stents could be exposed to angiotensin-converting enzyme (ACE) inhibitor drugs that are widely used for post-percutaneous coronary intervention patient therapy. This work investigates the inhibitory effect of an ACE inhibitor drug, namely captopril, on the corrosion behavior of Mg–Zn-(Y, Nd) alloys in Hanks' solution. Three alloy compositions, namely Mg–1Zn-2.9Y, Mg–5Zn-1Nd, and Mg–2Zn-0.2Y-0.5Nd, were prepared by a powder metallurgical (PM) method. The corrosion behavior and inhibition efficiency were studied using potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), Mott-Schottky analysis, and a hydrogen evolution test. It is shown that captopril suppressed the dissolution kinetics of Mg–Zn-(Y, Nd) alloys in Hanks' solution. The captopril inhibition efficiencies (η) for the alloys are in the order of Mg–2Zn-0.2Y-0.5Nd > Mg–5Zn-1Nd > Mg–1Zn-2.9Y. A remarkable η of 48.4 % has been achieved for the Mg–2Zn-0.2Y-0.5Nd alloy. The EIS results revealed that the polarization resistance increased in the alloys after the addition of captopril to Hanks' solution. The Mott-Schottky analysis showed that the Mg–Zn-(Y, Nd) alloys behaved as an n-type semiconductor but switched to a p-type for the Mg–1Zn-2.9Y alloy in the captopril-containing Hanks’ solution. The surface analysis of the post-corrosion-tested sample has observed captopril film partially covering the α-Mg matrix, which acted as a protective layer against corrosion.

View all citing articles on Scopus

^☆: Part of the Thermec’2009 Biodegradable Metals Special Issue, edited by Professor Diego Mantovani and Professor Frank Witte.

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ReviewDevelopments in metallic biodegradable stents☆

Abstract

Introduction

Section snippets

Idea of biodegradable stents

Development

In vitro and in vivo degradation studies

Concluding remarks

Lancet

Am J Cardiol

J Am Coll Cardiol

Lancet

Acta Biomater

Biomaterials

Biomaterials

Clin Chim Acta

Mol Aspects Med

Corros Sci

Biomaterials

Biomaterials

A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6–18 months after implantation into New Zealand white rabbits

Heart

Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?

Heart

First successful implantation of a biodegradable metal stent into the left pulmonary artery of a preterm baby

Catheter Cardiovasc Interv

Bioabsorbable metal stents for percutaneous treatment of critical recoarctation of the aorta in a newborn

Catheter Cardiovasc Interv

Preliminary results after application of absorbable metal stents in patients with critical limb ischemia

J Endovasc Ther

AMS INSIGHT—absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis

Cardiovasc Intervent Radiol

A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group

N Engl J Med

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators

N Engl J Med

Drug-eluting stents: caution and concerns for long-term outcome

Coron Artery Dis

In stent restenosis: bane of the stent era

J Clin Pathol

Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study

Circulation

Update on bioabsorbable stents: from bench to clinical

J Interv Cardiol

Update on in-stent restenosis

Curr Interv Cardiol Rep

Four-year experience with Palmaz-Schatz stenting in coronary angioplasty complicated by dissection with threatened or present vessel closure

Circulation

Coronary-artery stents

N Engl J Med

Review
Developments in metallic biodegradable stents☆