Cytotoxicity and its test methodology for a bioabsorbable nitrided iron stent

Abstract

Comprehensive assessments of the cytotoxicity of nitrided iron, a promising bioabsorbable metallic material, were conducted using in vitro methods. Extracting and standing experiments were conducted to determine the factors influencing the precipitation of the extract during extraction and incubation. The MTT method, fluorescent staining, and direct contact method were used to explore the in vitro cytotoxicity of nitrided iron stent extracts, nitrided iron foils, and their bulk corrosion products. The extracting and standing experiments confirmed that the extraction medium and available oxygen are crucial for precipitation during the extraction and incubation processes. In the MTT test, the extract of nitrided iron stents with a high iron ion concentration (124.11 ± 7.55 μg/mL) was not cytotoxic to L929 fibroblasts. Thus, the in vitro cytotoxicity of nitrided iron stents was actually caused by the size effect of corrosion particles and not the material itself. Test methodology for in vitro cytotoxicity of biodegradable iron-based materials was analyzed, and the results demonstrate that multiple methods should be combined for comprehensive evaluation of the cytocompatibility of bioabsorbable iron-based materials to get an impartial conclusion.

In vivo degradation and endothelialization of an iron bioresorbable scaffold

“…We made the IBS platform using pure iron alloyed with nitrogen. The alloying may increase the degradation rate and improve the mechanical properties [ 40 , 41 ]. The current sirolimus-eluting iron bioresorbable scaffolds (IBS Z8-P20 scaffolds, Φ3.0 × 8 mm & Φ3.0 × 15 mm, 800 nm zinc buffer layer, total coating thickness of both luminal and abluminal sides ~20 μm), IBS Z8-P13 scaffolds (Φ3.0 × 8 mm, 800 nm zinc buffer layer, total coating thickness ~13 μm), IBS Z6-P13 scaffolds (Φ3.0 × 8 mm, 600 nm zinc buffer layer, total coating thickness ~13 μm), and 316L stainless steel P13 stents (Φ3.0 × 8 mm, total coating thickness ~13 μm) shared the same ultrathin (53 μm) IBS platform design and sirolimus density (1.4 μm/mm 2 ).…”

Biodegradable Iron-Based Materials—What Was Done and What More Can Be Done?

“…Promising results were achieved by adding nitrogen to iron [ 111 ]. W. Lin et al published a series of studies about nitriding iron stents [ 70 , 112 , 113 ]. Nitrided iron turns out to corrode faster than pure iron and has better mechanical properties.…”

Are Fe-Based Stenting Materials Biocompatible? A Critical Review of In Vitro and In Vivo Studies

“…Few authors compared the consequences of the different procedures on cell cultures. Lin et al [35] compared the three methods for in vitro cytotoxicity evaluation, i.e., testing of extracts, direct contact, and the indirect contact method, and they reported completely opposite results. They showed a high fibroblast cytotoxicity after the direct exposure to corrosion particles precipitating during extraction or incubation processes, whereas the exposure to extracts (only iron ions) did not induce cytotoxicity.…”

“…Selecting a given cell type implies a specific scenario for the remodeling of the artery as each cell type has a different role and sensitivity. Some authors examined the response of cell types separately and found preferential cellular sensitivity [35,[43][44][45]. As restenosis is one of the principal adverse effects of stent implantation, some authors argue that elective cytotoxicity to VSMCs could antagonize restenosis by reducing excessive vascular cell proliferation [34].…”

“…Few authors have used human cell lines, highly relevant for the development of human endovascular implants, or primary cell lines, instead of animal cells, which are easier to handle and give more consistent results but are less closely related to the clinical situation [7,18,35,45].…”