Patrick K. Bowen

Zinc Exhibits Ideal Physiological Corrosion Behavior for Bioabsorbable Stents

Zinc is proposed as an exciting new biomaterial for use in bioabsorbable cardiac stents. Not only is zinc a physiologically relevant metal with behavior that promotes healthy vessels, but it combines the best behaviors of both current bioabsorbable stent materials: iron and magnesium. Shown here is a composite image of zinc degradation in a murine (rat) artery.

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

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.

Metallic zinc exhibits optimal biocompatibility for bioabsorbable endovascular stents

Although corrosion resistant bare metal stents are considered generally effective, their permanent presence in a diseased artery is an increasingly recognized limitation due to the potential for long-term complications. We previously reported that metallic zinc exhibited an ideal biocorrosion rate within murine aortas, thus raising the possibility of zinc as a candidate base material for endovascular stenting applications. This study was undertaken to further assess the arterial biocompatibility of metallic zinc. Metallic zinc wires were punctured and advanced into the rat abdominal aorta lumen for up to 6.5months. This study demonstrated that metallic zinc did not provoke responses that often contribute to restenosis. Low cell densities and neointimal tissue thickness, along with tissue regeneration within the corroding implant, point to optimal biocompatibility of corroding zinc. Furthermore, the lack of progression in neointimal tissue thickness over 6.5months or the presence of smooth muscle cells near the zinc implant suggest that the products of zinc corrosion may suppress the activities of inflammatory and smooth muscle cells.

Magnesium in the murine artery: Probing the products of corrosion

Many publications are available on the physiological and pseudophysiological corrosion of magnesium and its alloys for bioabsorbable implant application, yet few focus on the characterization of explanted materials. In this work, commercially pure magnesium wires were corroded in the arteries of rats for up to 1 month, removed, and both bulk and surface products characterized. Surface characterization using infrared spectroscopy revealed a duplex structure comprising heavily magnesium-substituted hydroxyapatite that later transformed into an A-type (carbonate-substituted) hydroxyapatite. To explain this transformation, an ion-exchange mechanism is suggested. Elemental mapping of the bulk products of biocorrosion revealed the elemental distribution of Ca, P, Mg and O in the outer and Mg, O and P in the inner layers. Carbon was not observed in any significant quantity from the inner corrosion layer, suggesting that carbonates are not a prevalent product of corrosion. Backscatter electron imaging of cross-sections showed that thinning or absence of the hydroxyapatite in the later stages of degradation is related to local thickening of the inner corrosion layer. Based on these experimental observations, mechanisms describing corrosion in the quasi-steady state and during terminal breakdown of the magnesium specimens are proposed.

Rates of in vivo (arterial) and in vitro biocorrosion for pure magnesium.

The development of magnesium-based materials for bioabsorbable stents relies heavily on corrosion testing by immersion in pseudophysiological solutions, where magnesium degrades faster than it does in vivo. The quantitative difference in corrosion kinetics in vitro and in vivo is largely unknown, but, if determined, would help reduce dependence on animal models. In order to create a quantitative in vitro-in vivo correlation based on an accepted measure of corrosion (penetration rate), commercially pure magnesium wires were corroded in vivo in the abdominal aortas of rats for 5-32 days, and in vitro for up to 14 days using Dulbeccos modified eagle medium. Cross-sectioning, scanning electron microscopy, image analysis, a modified penetration rate tailored to degraded wires, and empirical modeling were used to analyze the corroded specimens. In vitro penetration rates were consistently higher than comparable in vivo rates by a factor of 1.2-1.9× (±0.2×). For a sample <20% corroded, an approximate in vitro-in vivo multiplier of 1.3 ± 0.2× was applied, whereas a multiplier of 1.8 ± 0.2× became appropriate when the magnesium specimen was 25-35% degraded.

A new in vitro-in vivo correlation for bioabsorbable magnesium stents from mechanical behavior.

Correlating the in vitro and in vivo degradation of candidate materials for bioabsorbable implants is a subject of interest in the development of next-generation metallic stents. In this study, pure magnesium wire samples were corroded both in the murine artery (in vivo) and in static cell culture media (in vitro), after which they were subjected to mechanical analysis by tensile testing. Wires corroded in vivo showed reductions in strength, elongation, and the work of fracture, with additional qualitative changes between tensile profiles. The in vivo degradation was 2.2±0.5, 3.1±0.8, and 2.3±0.3 times slower than corrosion in vitro in terms of effective tensile strength, strain to failure, and sample lifetime, respectively. Also, a combined metric, defined as strength multiplied by elongation, was 3.1±0.7 times faster in vitro than in vivo. Consideration of the utility and restrictions of each metric indicates that the lifetime-based multiplier is the best suited to general use for magnesium, though other metrics could be used to deduce the mechanical properties of degradable implants in service.

Tensile testing as a novel method for quantitatively evaluating bioabsorbable material degradation

Bioabsorbable metallic materials have become a topic of interest in the field of interventional cardiology because of their potential application in stents. A well-defined, quantitative method for evaluating the degradation rate of candidate materials is currently needed in this area. In this study, biodegradation of 0.25-mm iron and magnesium wires was simulated in vitro through immersion in cell-culture medium with and without a fibrin coating (meant to imitate the neointima). The immersed samples were corroded under physiological conditions (37°C, 5% CO(2)). Iron degraded in a highly localized manner, producing voluminous corrosion product while magnesium degraded more uniformly. To estimate the degradation rate in a quantitative manner, both raw and corroded samples underwent tensile testing using a protocol similar to that used on polymeric nanofibers. The effective ultimate tensile stress (tensile stress holding constant cross-sectional area) was determined to be the mechanical metric that exhibited the smallest amount of variability. When the effective tensile stress data were aggregated, a statistically significant downward, linear trend in strength was observed in both materials (Fe and Mg) with and without the fibrin coating. It was also demonstrated that tensile testing is able to distinguish between the higher degradation rate of the bare wires and the lower degradation rate of the fibrin-coated wires with confidence.

Influence of Oxygen Concentration on the Performance of Ultra-Thin RF Magnetron Sputter Deposited Indium Tin Oxide Films as a Top Electrode for Photovoltaic Devices

The opportunity for substantial efficiency enhancements of thin film hydrogenated amorphous silicon (a-Si:H) solar photovoltaic (PV) cells using plasmonic absorbers requires ultra-thin transparent conducting oxide top electrodes with low resistivity and high transmittances in the visible range of the electromagnetic spectrum. Fabricating ultra-thin indium tin oxide (ITO) films (sub-50 nm) using conventional methods has presented a number of challenges; however, a novel method involving chemical shaving of thicker (greater than 80 nm) RF sputter deposited high-quality ITO films has been demonstrated. This study investigates the effect of oxygen concentration on the etch rates of RF sputter deposited ITO films to provide a detailed understanding of the interaction of all critical experimental parameters to help create even thinner layers to allow for more finely tune plasmonic resonances. ITO films were deposited on silicon substrates with a 98-nm, thermally grown oxide using RF magnetron sputtering with oxygen concentrations of 0, 0.4 and 1.0 sccm and annealed at 300 °C air ambient. Then the films were etched using a combination of water and hydrochloric and nitric acids for 1, 3, 5 and 8 min at room temperature. In-between each etching process cycle, the films were characterized by X-ray diffraction, atomic force microscopy, Raman Spectroscopy, 4-point probe (electrical conductivity), and variable angle spectroscopic ellipsometry. All the films were polycrystalline in nature and highly oriented along the (222) reflection. Ultra-thin ITO films with record low resistivity values (as low as 5.83 × 10−4 Ω·cm) were obtained and high optical transparency is exhibited in the 300–1000 nm wavelength region for all the ITO films. The etch rate, preferred crystal lattice growth plane, d-spacing and lattice distortion were also observed to be highly dependent on the nature of growth environment for RF sputter deposited ITO films. The structural, electrical, and optical properties of the ITO films are discussed with respect to the oxygen ambient nature and etching time in detail to provide guidance for plasmonic enhanced a-Si:H solar PV cell fabrication.

Evaluation of wrought Zn–Al alloys (1, 3, and 5 wt % Al) through mechanical and in vivo testing for stent applications

Special high grade zinc and wrought zinc-aluminum (Zn-Al) alloys containing up to 5.5 wt % Al were processed, characterized, and implanted in rats in search of a new family of alloys with possible applications as bioabsorbable endovascular stents. These materials retained roll-induced texture with an anisotropic distribution of the second-phase Al precipitates following hot-rolling, and changes in lattice parameters were observed with respect to Al content. Mechanical properties for the alloys fell roughly in line with strength (190-240 MPa yield strength; 220-300 MPa ultimate tensile strength) and elongation (15-30%) benchmarks, and favorable elastic ranges (0.19-0.27%) were observed. Intergranular corrosion was observed during residence of Zn-Al alloys in the murine aorta, suggesting a different corrosion mechanism than that of pure zinc. This mode of failure needs to be avoided for stent applications because the intergranular corrosion caused cracking and fragmentation of the implants, although the composition of corrosion products was roughly identical between non- and Al-containing materials. In spite of differences in corrosion mechanisms, the cross-sectional reduction of metals in murine aorta was nearly identical at 30-40% and 40-50% after 4.5 and 6 months, respectively, for pure Zn and Zn-Al alloys. Histopathological analysis and evaluation of arterial tissue compatibility around Zn-Al alloys failed to identify areas of necrosis, though both chronic and acute inflammatory indications were present.

Fabrication and Short-Term in Vivo Performance of a Natural Elastic Lamina-Polymeric Hybrid Vascular Graft

Although significant advances have been made in the development of artificial vascular grafts, small-diameter grafts still suffer from excessive platelet activation, thrombus formation, smooth muscle cell intimal hyperplasia, and high occurrences of restenosis. Recent discoveries demonstrating the excellent blood-contacting properties of the natural elastic lamina have raised the possibility that an acellular elastic lamina could effectively serve as a patent blood-contacting surface in engineered vascular grafts. However, the elastic lamina alone lacks the requisite mechanical properties to function as a viable vascular graft. Here, we have screened a wide range of biodegradable and biostable medical-grade polymers for their ability to adhere to the outer surface of the elastic lamina and allow cellular repopulation following engraftment in the rat abdominal aorta. We demonstrate a novel method for the fabrication of elastic lamina-polymeric hybrid small-diameter vascular grafts and identify poly(ether urethane) (PEU 1074A) as ideal for this purpose. In vivo results demonstrate graft patency over 21 days, with low thrombus formation, mild inflammation, and the general absence of smooth muscle cell hyperplasia on the grafts luminal surface. The results provide a new direction for developing small-diameter vascular grafts that are mass-producible, shelf-stable, and universally compatible due to a lack of immune response and inhibit the in-graft restenosis response that is common to nonautologous materials.