Recent advances in Fe-based bioresorbable stents: Materials design and biosafety

Abstract

Fe-based materials have received more and more interests in recent years as candidates to fabricate bioresorbable stents due to their appropriate mechanical properties and biocompatibility. However, the low degradation rate of Fe is a serious limitation for such application. To overcome this critical issue, many efforts have been devoted to accelerate the corrosion rate of Fe-based stents, through the structural and surface modification of Fe matrix. As stents are implantable devices, the released corrosion products (Fe²⁺ ions) in vessels may alter the metabolism, by generating reactive oxygen species (ROS), which might in turn impact the biosafety of Fe-based stents. These considerations emphasize the importance of combining knowledge in both materials and biological science for the development of efficient and safe Fe-based stents, although there are still only limited numbers of reviews regarding this interdisciplinary field. This review aims to provide a concise overview of the main strategies developed so far to design Fe-based stents with accelerated degradation, highlighting the fundamental mechanisms of corrosion and the methods to study them as well as the reported approaches to accelerate the corrosion rates. These approaches will be divided into four main sections, focusing on (i) increased active surface areas, (ii) tailored microstructures, (iii) creation of galvanic reactions (by alloying, ion implantation or surface coating of noble metals) and (iv) decreased local pH induced by degradable surface organic layers. Recent advances in the evaluation of the in vitro biocompatibility of the final materials and ongoing in vivo tests are also provided.

Graphical abstract

Fig. 1

The illustrative scheme of equipments for surface and structure analysis in the domain of Fe-based BRS. Created with Biorender.

Fig. 2

Illustrative scheme of the strategies to accelerate iron corrosion via (i) increasing surface porosity and roughness; (ii) Creating fine grained microstructure; (iii) alloying or ion implantation; and (iv) surface coating of microgalvanic layer or polymer to decrease local pH or/and inhabit of passivation layer deposition. Created with Biorender.

Fig. 3

(A) Construction of 3D macroporous Fe structure from computerized tomography (CT) scan and SEM picture of microporous sample surface. Comparison of potentio-dynamic polarization curves for (b) dense and microporous Fe sample (S1–S3), (c) macroporous samples (TO) with different strut size. Adapted from Ref. [39], copyright 2019, Elsevier.

Fig. 4

The yield (YS), ultimate (US) strength and elongation values of (a) as-cast and (b) as-rolled Fe and Fe-X (X = Mn, Co, Al, W, Sn, B, C and S) alloys. Adapted from Ref. [36], copyright 2011, Elsevier. (c) The potentio-dynamic polarization curves and SEM images after static immersion tests of 24 h for Fe, Fe₈₇Mg₉Zn₄, Fe₇₄Mg₁₉Zn₇ and Fe₆₀Mg₃₀Zn₁₀ alloys. Adapted from Ref. [61] copyright 2022, Elsevier. (d) 3D height image representing the surface topography of laser-textured and polished Fe–Mn sample before and after 3 days of immersion. Adapted from Ref. [47] copyright 2018, Elsevier. (e) Polarization curve for Fe and Fe/CNTs alloys (0.3–0.9 wt% CNTs contents). (f) Corrosion rate from 28 days' immersion tests for Fe/CNTs samples and (g) SEM image for Fe/1.2CNTs sample after immersion test. Adapted from Ref. [62], copyright 2019, Elsevier.

Fig. 5

(A) The EDX mapping of Zn ion implanted Fe; (inset) the mass and atomic contents of Fe and Zn in the mapping area. (b) Polarization curves and (c) static immersion tests for pure and Zn-implanted Fe. Adapted from Ref. [68] copyright (2016), Oxford University Press. (d) AFM image with surface roughness (Ra) values for pure and Zn-implanted Fe (Zn–Fe-10 sample, ion dose = 10 × 10¹⁶ ions/cm²). (b) Polarization curves and SEM images for (f) Fe, (g) Zn–Fe-10 sample after 9 days immersion test. Adapted from Ref. [49] copyright 2017, Elsevier. (h) SEM image and (inset) EDX map for Ta–Fe sample. (i) The atomic composition of Fe and Ta at P1, P2 and P3 points in the SEM image. (j) Polarization curves, (k) analysis of average degradation depth and released Fe ion concentration during static immersion tests for Fe and Ta–Fe sample. Adapted from Ref. [45] copyright 2022, Elsevier.

Fig. 6

SEM images of (a) Pt- (discs diameter of 4 μm; the space of 4 μm between two nearest platinum discs) and (b) Au-coated (prepared by a quasi-circular template with 200 × 200 μm² size) Fe. Dynamic-potentio polarization curves for (c) Pt- and (d) Au-coated Fe. (e) The corrosion rate values from static immersion tests for 42 days for Pt-coated Fe. (f) Released Fe ion concentration during 30 days immersion test for Au-coated Fe. (a, c, e) Adapted from Ref. [21] copyright 2016, Springer Nature. (b, d, f) Adapted from Ref. [20] copyright 2015, Elsevier.

Fig. 7

(A) Local pH on the surface of bare iron, in the interfaces of PMMA- and PLA-coated iron after 24 h immersion in Hank's solution. (b) Illustration of hydrolysis of PLA. Corrosion (c) potential and (d) current, derived from polarization curves, for bare, PMMA- and PLA-coated Fe after immersion in Hank's solution. (e) SEM and EDX mapping for PLA-coated iron after immersion (72 h in Hank's solution). Adapted from Ref. [51], copyright 2019, American Chemical Society.

Fig. 8

Schematic representation of in vitro tests for the biocompatibility evaluation of Fe samples (a) MTT test of ADSCs for indirect contact evaluation of iron released products (b). Adapted from Ref. [74] for (b), copyright 2021, Elsevier.

Fig. 9

Illustration of dynamic systems for the evaluation of iron samples. Mock vessels (a) or arteries (b) under simulated physiological flow. Adapted from Ref. [80]. Degradation under static (c) or dynamic (d) conditions of iron surfaces. Adapted from Ref. [35], 2010, Elsevier.

Fig. 10

(1) MG-63 cells on Ti–6Al–4V (a, b) and iron (c, d) scaffolds; live cells, green; dead cells, red. Scale bars indicate 300 mm (a, c) and 30 mm (b, d) (adapted from Ref. [40]). (2) Preosteoblasts after 3 days of culture in (a) 100%, (b) 75%, and (c) 50% iron extracts, (a–c) rhodamine phalloidin (red) and DAPI (blue) stained; morphology of the cells after 3 days of direct cell culture on the iron scaffolds (d-f) calcein acetoxymethyl (green, indicating living cells) and ethidium homodimer-1 (red, indicating dead cells) (adapted from Ref. [46]). (3) Corrosion of iron stent produces ROS by the Fenton reaction that can induce a cascade of oxidations on cell components.