Nickel ions from a corroded cardiovascular stent induce monocytic cell apoptosis: Proposed impact on vascular remodeling and mechanism.

BACKGROUND/PURPOSE: Monocytes play important roles in inflammatory responses and vascular remodeling after vascular stenting. This research focused on impacts of nickel (Ni) ions released from a corroded cardiovascular stent on cytotoxicity and monocyte activation. METHODS: A human promonocytic (macrophage-like) cell line (U937) was exposed to graduated concentrations of Ni(2+)in vitro. Cells were observed and harvested at indicated times to determine the effects using histological and biochemical methods. RESULTS: Ni caused U937 cell death in dose- and time-dependent manners. In vitro, high concentrations of Ni(2+) (>240 µM) significantly induced cell apoptosis and increased terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-positive cells according to flow cytometric surveillance and triggered apoptotic cell death. Although no significant changes in Bcl-2 or Bax expressions were detected after 24 hours of Ni(2+) treatment, increasing cleavage of caspase-3 and -8 was present. Results showed that cleavage of caspase-8 was inhibited by the presence of the inhibitor, Z-IETD-FMK, and this suggested the presence of Ni(2+)-induced U937 cell death through a death receptor-mediated pathway. Simultaneously, when treated with a high concentration of Ni(2+) ions, expressions of the vascular remodeling factors, matrix metalloproteinases (MMP)-9 and -2, were activated in dose- and time-dependent manners. Secretion of the proliferative factor, monocyte chemoattractant protein (MCP)-1, significantly increased during the first 6 hours of incubation with 480 µM Ni(2+)-treated medium. CONCLUSION: Our results demonstrated that a high concentration of Ni ions causes apoptotic cell death of circulating monocytes. They may also play different roles in vascular remodeling during the corrosion process following implantation of Ni alloy-containing devices.

Stability of passivated 316L stainless steel oxide films for cardiovascular stents.

Passivated 316L stainless steel is used extensively in cardiovascular stents. The degree of chloride ion attack might increase as the oxide film on the implant degrades from exposure to physiological fluid. Stability of 316L stainless steel stent is a function of the concentration of hydrated and hydrolyated oxide concentration inside the passivated film. A high concentration of hydrated and hydrolyated oxide inside the passivated oxide film is required to maintain the integrity of the passivated oxide film, reduce the chance of chloride ion attack, and prevent any possible leaching of positively charged ions into the surrounding tissue that accelerate the inflammatory process. Leaching of metallic ions from corroded implant surface into surrounding tissue was confirmed by the X-ray mapping technique. The degree of thrombi weight percentage [W(ao): (2.1 +/- 0.9)%; W(ep): (12.5 +/- 4.9)%, p < 0.01] between the amorphous oxide (AO) and the electropolishing (EP) treatment groups was statistically significant in ex-vivo extracorporeal thrombosis experiment of mongrel dog. The thickness of neointima (T(ao): 100 +/- 20 microm; T(ep): 500 +/- 150 microm, p < 0.01) and the area ratio of intimal response at 4 weeks (AR(ao): 0.62 +/- 0.22; AR(ep): 1.15 +/- 0.42, p < 0.001) on the implanted iliac stents of New Zealand rabbit could be a function of the oxide properties.

Mechanism of degradation of AgCl coating on biopotential sensors.

AgCl coated Ag foil has been widely used as the biopotential sensor to diagnose problems of the human heart. Evidence shows that quality of AgCl on the electrode could experience degradation during the process of long-term monitoring for irregular activities of the heart. To study the degradation of AgCl/Ag electrode, new and used electrodes were collected. Electrochemical tests such as open-circuit potential (OCP), cathodic stripping, electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and X-ray mapping of elemental distribution were applied to understand the electrochemical properties of the sensors during the progress of degradation. Results revealed that OCP values shift from positive potential of new sensor to negative potential of used sensor (OCP(new): +30 mV; OCP(used): -300 mV, p < 0.05) and a significant difference in impedance (Impedance(new): 3000 Omega; Impedance(used): 1 MOmega, p < 0.05). Ratio of the average AgCl thickness on good and bad eletrocardiographic (ECG or EKG) electrodes is 4.83 (p < 0.05). Simulated degradation by exposing the biosensor to deaerated sweat solution and by cathodic stripping of AgCl proposed that the degradation occurs by cathodic reduction of AgCl due to the presence of hydrogen ions in the low pH value of human sweat under deaerated condition.

Nanoporous hard carbon membranes for medical applications.

Current blood glucose sensors have proven to be inadequate for long term in vivo applications; membrane biofouling and inflammation play significant roles in sensor instability. An ideal biosensor membrane material must prevent protein adsorption and promote integration of the sensor with the surrounding tissue. Furthermore, biosensor membranes must be sufficiently thin and porous in order to allow the sensor to rapidly respond to fluctuations in analyte concentration. In this study, the use of diamondlike carbon-coated anodized aluminum oxide as a potential biosensor membrane is discussed. Diamondlike carbon films and diamondlike carbon-coated anodized aluminum oxide nanoporous membranes were examined using scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and platelet rich plasma testing. The diamondlike carbon-coated anodized aluminum oxide membranes remained free from protein adsorption during in vitro platelet rich plasma testing. We anticipate that this novel membrane could find use in immunoisolation devices, pacemakers, kidney dialysis membranes, microdialysis systems, and other devices facing biocompatibility issues that limit in vivo function.

Failure analysis of explanted sternal wires.

To classify and understand the mechanisms of surface damages and fracture mechanisms of sternal wires, explanted stainless steel sternal wires were collected from patients with sternal dehiscence following open-heart surgery. Surface alterations and fractured ends of sternal wires were examined and analyzed. Eighty fractured wires extracted from 25 patients from January 1999 to December 2003, with mean implantation interval of 55+/-149 days (range 5-729 days) after cardiac surgery, were studied by various techniques. The extracted wires were cleaned and the fibrotic tissues were removed. Irregularities and fractured ends were assayed by a scanning electron microscopy. After stereomicroscopy and documentation, the explants were cleaned with 1% sodium hypochlorite to remove the blood and tissues and was followed by cleaned with deionized water and alcohol. The explants were examined by stereomicroscopy, and irregularities on surface and fracture surfaces of sternal wires were assayed by scanning electron microscopy, energy dispersive X-ray analysis (EDAX) and X-ray mapping. The explants with surrounding fibrotic tissue were stained and examined with stereomicroscopy and transmission electronic microscopy. Corrosion pits were found on the surface of explanted sternal wires. EDAX and X-ray mapping examinations revealed diminution of nickel concentration in the severely corroded pits on sternal wires. A feature of transgranular cracking was observed for stress corrosion cracking and striation character for typical corrosion fatigue was also identified. TEM examination of tissue showed the metallic particles in phagolysosomes of macrophages inside the surrounding sternal tissue. The synergic effect of hostile environment and the stress could be the precursors of failures for sternal wires.

Amorphous oxide--a platform for drug delivery.

Usually, a drug is loaded onto the metallic surface of a medical device by applying a polymer layer containing the drug. Unfortunately, polymer coatings on the metallic surface may exhibit numerous problems after implantation, such as late thrombosis, inflammation, and restenosis. Current research was conducted to investigate whether a suitable oxide layer can be used as a polymer-free platform for drug loading, especially for cardiovascular stents. The loading of heparin onto, as well as eluting of heparin from, the amorphous oxide film on the 316LVM stainless steel wire was confirmed by experimental studies using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), electron spectroscopy for chemical analysis (ESCA), high-performance liquid chromatography (HPLC), and activated clotting time (ACT). Evidence shows that amorphous oxide can be an ideal substitute for the polymer coating of drug-loaded stents to minimize metallic corrosion, inflammation, late-thrombosis, and restenosis.

In vitro study of drug loading on polymer-free oxide films of metallic implants.

Traditionally, a drug that is loaded onto a metallic surface has to use various polymer bondings as its platform. Unfortunately, polymer coatings on a metallic surface cause numerous problems after implantation, such as late thrombosis, inflammation, and restenosis. This research was conducted to investigate whether an oxide layer can be used as a polymer-free platform for drug loading, especially for cardiovascular stents. The interaction and loading of heparin onto different oxide films on 316LVM stainless steel wire was confirmed in vitro by experimental studies using linear voltammetry, electrochemical impedance spectroscopy, and electron spectroscopy for chemical analysis. The eluting of heparin from heparinized surface was studied by using high-performance liquid chromatography, and activated clotting time in addition to linear voltammetry and electron spectroscopy for chemical analysis analyses. Experimental results show that amorphous oxide could be a potential substitute for the polymer coating of drug-loaded stents for minimizing metallic corrosion, inflammation, late thrombosis, and restenosis.

The interaction of selected semiconducting biomaterials with platelet-rich plasma and whole blood.

Copper and silicon are used as biomaterials in various forms. Silicon is a well-known semiconductor and has two distinct types (n-type and p-type), depending on the dopants used. The oxides (e.g., CuO and Cu2O) on the copper surface also behave as semiconductors. The electrochemical properties of these two selected semiconducting biomaterials were investigated by cyclic voltammetry, electrochemical impedance spectroscopy (EIS), and open-circuit potential (OCP) in an aerated Ringer's solution at 37 degrees C. Platelet-rich plasma (PRP) and whole blood from a healthy human donor were used to determine the degree of interaction with the selected semiconducting materials in vitro. Morphologies of adherent platelets and blood on these two biomaterials were examined by scanning electron microscopy (SEM). Experimental results indicated that the degree of interaction is a function of the electrochemical properties of these two biomaterials. Platelets and blood were found to react strongly with p-type biomaterials while little or no sign of interaction with n-type biomaterials was demonstrated. The difference in PRP and whole blood reactions between p-type and n-type semiconductors was quantified to be significant as p<0.05.

Quantitative evaluation of thrombosis by electrochemical methodology.

Electrochemical reactions between blood and metal electrodes have been studied since 1928. Little is known about the actual current density induced during the reaction. In this study, an in situ continuous monitoring method was developed to detect the progress of thrombosis on an oxidized 316L stainless steel coil was deployed inside the artery. Three stages of current density were observed on a 316L wire passivated with polycrystalline oxide film. In contrast, no significant current density was detected for a wire passivated with amorphous oxide film. Results showed that this in situ electrochemical monitoring method is sensitive to the passivated film on the stainless steel coil and could provide efficient and reliable information on the control of thrombosis on cardiovascular devices.

Impact on the thrombogenicity of surface oxide properties of 316l stainless steel for biomedical applications.

Surface oxide film on cardiovascular devices could be one of the most critical factors that determine the degree of thrombosis. Previous studies have shown that metallic wire passivated with amorphous oxide film provides excellent corrosion and scratch resistance. Investigation was undertaken to see whether this oxide film, with its unique electrochemical properties, could reduce the development of thrombosis. Results show that amorphous oxide has higher value of time constant, lower open-circuit potential, and lower degree of thrombosis. These distinguished characteristics prove amorphous oxide to be the best candidate for the cardiovascular devices. Amorphous oxide film could be a potential solution to the thrombogenic problem of cardiovascular devices.

Potential risk of sternal wires.

OBJECTIVE: To understand the potential fracture mechanism of sternal wires, we collected extracted stainless steel sternal wires from patients with sternal dehiscence following open-heart operations. Surface alterations and fractured ends of sternal wires were inspected and analyzed. METHODS: Eight fractured and 12 non-fractured wires extracted from five patients (closure method: figure-of-eight or straight twisted; two without and three with mediastinitis) with mean implantation interval of 13.2+/-4.2 days (range 8-20 days) were studied by various techniques. The extracted wires were cleaned and the fibrotic tissues were removed. Irregularities and fractured ends were assayed by scanning electron microscopy and energy dispersive X-ray analysis (EDXA). RESULTS: All examined fractured wires showed the presence of severe transversal cracks and crevice corrosion. EDAX revealed aluminum oxide inclusion on the fractured surface. CONCLUSIONS: The synergic effect of stress and poor wire quality could be the precursors of material failure for the sternal wire.

Atomic layer deposition of titanium dioxide on cellulose acetate for enhanced hemostasis.

TiO2 films may be used to alter the wettability and hemocompatibility of cellulose materials. In this study, pure and stoichiometric TiO2 films were grown using atomic layer deposition on both silicon and cellulose substrates. The films were grown with uniform thicknesses and with a growth rate in agreement with literature results. The TiO2 films were shown to profoundly alter the water contact angle values of cellulose in a manner dependent upon processing characteristics. Higher amounts of protein adsorption indicated by blurry areas on images generated by scanning electron microscopy were noted on TiO2 -coated cellulose acetate than on uncoated cellulose acetate. These results suggest that atomic layer deposition is an appropriate method for improving the biological properties of hemostatic agents and other blood-contacting biomaterials.

Degradation of 316L stainless steel sternal wire by steam sterilization.

Sterilization is an important step prior to the implantation of medical devices inside the human body. In this work we studied the influence of steam sterilization cycles on the oxide film properties of stainless steel sternal wire. Characterization techniques such as open- circuit potential, potentiodynamic measurement, electrochemical impedance spectroscopy, cathodic stripping, transmission electron microscopy, atomic force microscopy and scanning electron microscopy were employed to investigate the cycles of steam sterilization on the corrosion behavior of sternal wire. The results showed that the oxide properties are a function of the number of steam sterilization cycles and deteriorate as the number of cycles increases. Steam sterilization might damage the implant integrity and heavy metals could be released to the surrounding tissues due to deterioration of the oxide film.

Two Photon Polymerization-Micromolding of Polyethylene Glycol-Gentamicin Sulfate Microneedles.

The use of microneedles for transdermal drug delivery is limited due to the risk of infection associated with formation of channels through the stratum corneum layer of the epidermis. The risk of infection associated with use of microneedles may be reduced by imparting these devices with antimicrobial properties. In this study, a photopolymerization-micromolding technique was used to fabricate microneedle arrays from a photosensitive material containing polyethylene glycol 600 diacrylate, gentamicin sulfate, and a photoinitiator. Scanning electron microscopy indicated that the photopolymerization-micromolding process produced microneedle arrays that exhibited good microneedle-to-microneedle uniformity. An agar plating assay revealed that microneedles fabricated with polyethylene glycol 600 diacrylate containing 2 mg mL(-1) gentamicin sulfate inhibited growth of Staphylococcus aureus bacteria. Scanning electron microscopy revealed no platelet aggregation on the surfaces of platelet rich plasma-exposed undoped polyethylene glycol 600 diacrylate microneedles and gentamicin-doped polyethylene glycol 600 diacrylate microneedles. These efforts will enable wider adoption of microneedles for transdermal delivery of pharmacologic agents.

Atomic layer deposition-based functionalization of materials for medical and environmental health applications.

Nanoporous alumina membranes exhibit high pore densities, well-controlled and uniform pore sizes, as well as straight pores. Owing to these unusual properties, nanoporous alumina membranes are currently being considered for use in implantable sensor membranes and water purification membranes. Atomic layer deposition is a thin-film growth process that may be used to modify the pore size in a nanoporous alumina membrane while retaining a narrow pore distribution. In addition, films deposited by means of atomic layer deposition may impart improved biological functionality to nanoporous alumina membranes. In this study, zinc oxide coatings and platinum coatings were deposited on nanoporous alumina membranes by means of atomic layer deposition. PEGylated nanoporous alumina membranes were prepared by self-assembly of 1-mercaptoundec-11-yl hexa(ethylene glycol) on platinum-coated nanoporous alumina membranes. The pores of the PEGylated nanoporous alumina membranes remained free of fouling after exposure to human platelet-rich plasma; protein adsorption, fibrin networks and platelet aggregation were not observed on the coated membrane surface. Zinc oxide-coated nanoporous alumina membranes demonstrated activity against two waterborne pathogens, Escherichia coli and Staphylococcus aureus. The results of this work indicate that nanoporous alumina membranes may be modified using atomic layer deposition for use in a variety of medical and environmental health applications.