A simplified in vivo approach for evaluating the bioabsorbable behavior of candidate stent materials

Abstract

Metal stents are commonly used to revascularize occluded arteries. A bioabsorbable metal stent that harmlessly erodes away over time may minimize the normal chronic risks associated with permanent implants. However, there is no simple, low-cost method of introducing candidate materials into the arterial environment. Here, we developed a novel experimental model where a biomaterial wire is implanted into a rat artery lumen (simulating bioabsorbable stent blood contact) or artery wall (simulating bioabsorbable stent matrix contact). We use this model to clarify the corrosion mechanism of iron (≥99.5 wt %), which is a candidate bioabsorbable stent material due to its biocompatibility and mechanical strength. We found that iron wire encapsulation within the arterial wall extracellular matrix resulted in substantial biocorrosion by 22 days, with a voluminous corrosion product retained within the vessel wall at 9 months. In contrast, the blood-contacting luminal implant experienced minimal biocorrosion at 9 months. The importance of arterial blood versus arterial wall contact for regulating biocorrosion was confirmed with magnesium wires. We found that magnesium was highly corroded when placed in the arterial wall but was not corroded when exposed to blood in the arterial lumen for 3 weeks. The results demonstrate the capability of the vascular implantation model to conduct rapid in vivo assessments of vascular biomaterial corrosion behavior and to predict long-term biocorrosion behavior from material analyses. The results also highlight the critical role of the arterial environment (blood vs. matrix contact) in directing the corrosion behavior of biodegradable metals.

New approaches in evaluating metallic candidates for bioabsorbable stents

“…From the iron/oxygen map, one can see that a significant amount of iron oxide has developed between the passive layer and the remaining Fe. These results are indicative of the evolution of a voluminous Fe-O corrosion product, which was confirmed by histological examination 54 and by results presented later in Figure 5. The corrosion products do not appear to be excreted nor metabolized at an appreciable rate.…”

“…Specific preparation, sterilization, and related procedures can be found in the authors' previous contribution. 54 The position of the wire in the arterial wall or in the lumen determines the nature and composition of the wire's environment, which greatly influences the corresponding degradation that occurs. Positioning the wire in the lumen replicates the conditions a stent experiences during its early life, before it becomes encapsulated in neointimal tissue.…”

“…Instead of dissolving in an apparently harmless manner, pure Fe seems to be unsuitable for application in interventional cardiology due to the accumulation of voluminous corrosion products in the arterial walls of rats. 54 Mg has not exhibited the same buildup of corrosion product, but instead appeared to dissolve harmlessly, 54 suggesting that Mg and its alloys are currently the most promising bioabsorbable materials.…”

“…Fe extracted from the luminal environment ( Figure 5(e)) appears to be lightly corroded, while the wall contacting surfaces on a portion of the Fe sample in Figure 5(f) have ballooned outwards because of the evolution of a voluminous corrosion product. 54 The precise reason for this difference between the luminal and wall environment with respect to material degradation is currently unknown. However, it will likely play a key role in the evaluation of bioabsorption, as the pre and postencapsulation degradation rate of any candidate biomaterial will differ in a manner similar to the wires presented in Figure 5.…”

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

“…8 Iron, on the other hand, degrades too slowly for many applications and produces voluminous corrosion products, causing an increase in the volume of the implant. 9,10 Zinc (Zn) was recently suggested as an alternative degradable metal or alloy base. 11,12 The toxicity of zinc is higher than that of iron or magnesium, and concerns have therefore been raised regarding its biocompatibility.…”