Bioresorbable stents

In medicine, a stent is any device which is inserted into a blood vessel or other internal duct in order to expand the vessel to prevent or alleviate a blockage. Traditionally, such devices are fabricated from metal mesh and remain in the body permanently or until removed through further surgical intervention. A bioresorbable, biodegradable, or bioabsorbable stent serves the same purpose, but is manufactured from a material that may dissolve or be absorbed in the body.

Background
The use of metal drug-eluting stents presents some potential drawbacks. These include a predisposition to late stent thrombosis, prevention of late vessel adaptive or expansive remodeling, hindrance of surgical revascularization, and impairment of imaging with multislice CT.

To overcome some of these potential drawbacks, several companies are pursuing the development of bioresorbable or bioabsorbable stents. Like metal stents, placement of a bioresorbable stent will restore blood flow and support the vessel through the healing process. However, in the case of a bioresorbable stent, the stent will gradually resorb and be benignly cleared from the body, leaving no permanent implant.

Studies have shown that the most critical period of vessel healing is largely complete by approximately three months. Therefore, the goal of a bioresorbable or “temporary” stent is to fully support the vessel during this critical period, and then resorb from the body when it is no longer needed.

Material Selection
Selection of a base material for a bioabsorbable stent is not a trivial task; most traditional biocompatible base metals, such as tantalum, titanium, chromium, et al. do not degrade at an appreciable rate in the body due to passivation and thus would not be absorbed in a reasonable amount of time. Furthermore, such extraphysiological elements would not be metabolized by the body, but would rather have to proceed directly to excretion. Conversely, elements that are already known to play physiological roles in the human body are generally biocompatible in their metallic forms and therefore are suitable materials for constructing bioabsorbable stents. The two primary stent material candidates are magnesium, iron, and their alloys.

Iron
Iron stents were shown using an in vivo evaluation method based on the murine abdominal aorta to generate an iron oxide-filled cavity in the vascular wall. This behavior significantly narrowed the lumen and generated a potential site for rupture of the endothelium after stent degradation.

Magnesium
Magnesium is a relatively new biomaterial that has recently been gaining traction. While degrading harmlessly, it has been shown to possess a functional degradation time of about 30 days in vivo. This is much short of the three-to-six month window desired for bioabsorbable stents. Thus, much attention has been given to drastically reducing the rate of magnesium corrosion by alloying, coating, etc. Many novel methods have surfaced to minimize the penetration rate and hydrogen evolution rate (or, in layman's terms, the corrosion rate). One of the most successful has involved the creation of bioabsorbable metallic glasses via rapid solidification. Other, alternative solutions have included the development of magnesium-rare earth (Mg-RE) alloys which benefit from the low cytotoxicity of RE elements. Coatings and sophisticated materials processing routes are currently being developed to further decrease the corrosion rate. However a number of issues remain limiting the further development of Mg biomaterials in general.

Zinc
Recently, zinc was shown to exhibit outstanding physiological corrosion behavior, meeting a benchmark penetration rate of 20 micrometers per year. This contribution also asserts that zinc alloys generally meet or exceed mechanical behavior benchmarks (i.e. ductility and tensile strength). While promising, this material is relatively new, so further work is required to prove that zinc is a feasible base material for a stent.

Testing Bioabsorbable Materials
Testing bioabsorbable materials is a special challenge. Many researchers prefer to use in vitro corrosion simulations using pseudo-physiological solutions such as EMEM or HBSS. It is a point of contention, however, whether or not these solutions accurately mimic degradation in the mammillian artery. One methodological summary of in vitro corrosion concluded that DMEM, a variant of EMEM, was a suitable corrosion solution; summarized in vivo methodology and its application to magnesium alloys; reported several embodiments of in vitro corrosion tests; and argued in favor of tensile testing as a means for quantitative assessment of degradation. The variants of in vitro corrosion included typical bare wire submersion, submersion of a fibrin-coated wire, and laminar flow over a similarly coated specimen, with each approach having unique advantages. The argument for tensile testing was built on a prior publication, which demonstrated that measuring the effective tensile strength of samples with a wire geometry resulted in data that was sensitive to different materials and different corrosive environments.