Yeoheung Yun

Revolutionizing biodegradable metals

Development of biodegradable metal implants is a complex problem because it combines engineering and medical requirements for a material. This article discusses the development of sensing and corrosion control techniques that can help in the design of biodegradable metallic implants. Biodegradable metallic implants dissolve as new tissue is formed. One of the most important factors in the design of biodegradable implants is to study the active interface, which should be monitored and controlled to address the medical concern of biocompatibility. Thus miniaturized and nanotechnology-based sensors that measure the activities of the degradation process and the formation of tissue are discussed for use with in vitro and in vivo experiments. These sensors can monitor chemical components and also cell activity and can provide new knowledge about biodegradable interfaces and how to actively control the interface to provide the best bioactivity to regenerate new tissue in a short time. Development of new alloys, nano-materials, miniature sensors, corrosion control coatings, and auxiliary applications such as biodegradable drug delivery capsules is expected to open up a new era in the engineering of materials for medicine.

Nanotube electrodes and biosensors

This article reviews the state of the art in carbon nanotube electrode and biosensor research. Carbon nanotubes have unique mechanical, electrical, and geometrical properties that are ideal for developing different types of nanoscale electrodes and biosensors. Carbon nanotube synthesis and subsequent functionalization strategies to immobilize special biomolecules are discussed first. Then different types of carbon nanotube biosensors and electroanalytical methods are reviewed particularly considering their capabilities for low detection limits, point-of-care applications, and label-free use. Detection strategies for proteins and nucleic acids, as well as mammalian and bacterial cells are also outlined. We conclude with some speculations and predictions on future exciting and challenging directions for nanotube biosensor research and applications.

Development of novel single-wall carbon nanotube?epoxy composite ply actuators

This paper describes a carbon nanotube epoxy ply material that has electrochemical actuation properties. The material was formed by dispersing single-wall carbon nanotubes in a solvent and then solution casting a thin paper using a mold and vacuum oven. In order to take advantage of the high elastic modulus of carbon nanotubes for actuation, epoxy as a chemically inert polymer is considered. An epoxy layer was cast on the surface of the nanotube paper to make a two-layer ply. A wet electrochemical actuator was formed by placing the nanotube epoxy ply in a 2 M NaCl electrolyte solution. Electrochemical impedance spectroscopy and cyclic voltammetry were carried out to characterize the electrochemical properties of the actuator. The voltage–current relationship and power to drive the actuator material were also determined. Compared to previous single-wall carbon nanotube buckypaper tape actuators, which had poor adhesion between the nanotubes and tape, and other nanotube–thermal plastic polymer actuators, which could not provide high strength, the epoxy based actuator has a higher elastic modulus and strength, which will be useful for future structural applications. This demonstrates that a polymer layer can reinforce nanotube paper, which is an important step in building a new structural material that actuates. Further work is under way to develop a solid electrolyte to allow dry actuation. Finally, these actuator plies will be laminated to build a carbon nanocomposite material. This smart structural material will have potential applications that range from use in robotic surgical tools to use as structures that change shape.

In Vivo and In Vitro Degradation Behavior of Magnesium Alloys as Biomaterials

The corrosion behavior of pure Mg, AZ31, and AZ91D were evaluated in various in vitro and in vivo environments to investigate the potential application of these metals as biodegradable implant materials. DC polarization tests and immersion tests were performed in different simulated body solutions, such as distilled (DI) water, simulated body fluid (SBF) and phosphate buffered solution (PBS). Mg/Mg alloys were also implanted in different places in a mouse for in vivo weight loss and biocompatibility investigations. The in vivo subcutis bio-corrosion rate was lower than the corrosion rate for all of the in vitro simulated corrosive environments. The Mg/Mg alloys were biocompatible based on histology results for the liver, heart, kidney, skin and lung of the mouse during the two months implantation. Optical microscopy and scanning electron microscopy were carried out to investigate the morphology and topography of Mg/Mg alloys after immersion testing and implantation to understand the corrosion mechanisms.

Electrochemical impedance measurement of prostate cancer cells using carbon nanotube array electrodes in a microfluidic channel

Highly aligned multi-wall carbon nanotubes were synthesized in the shape of towers and embedded into fluidic channels as electrodes for impedance measurement of LNCaP human prostate cancer cells. Tower electrodes up to 8 mm high were grown and easily peeled off a silicon substrate. The nanotube electrodes were then successfully soldered onto patterned printed circuit boards and cast into epoxy under pressure. After polishing the top of the tower electrodes, RF plasma was used to enhance the electrocatalytic effect by removing excess epoxy and activating the open end of the nanotubes. Electrodeposition of Au particles on the plasma-treated tower electrodes was done at a controlled density. Finally, the nanotube electrodes were embedded into a polydimethylsiloxane (PDMS) channel and electrochemical impedance spectroscopy was carried out with different conditions. Preliminary electrochemical impedance spectroscopy results using deionized water, buffer solution, and LNCaP prostate cancer cells showed that nanotube electrodes can distinguish the different solutions and could be used in future cell-based biosensor development.

KCa3.1 and TRPM7 Channels at the Uropod Regulate Migration of Activated Human T Cells

The migration of T lymphocytes is an essential part of the adaptive immune response as T cells circulate around the body to carry out immune surveillance. During the migration process T cells polarize, forming a leading edge at the cell front and a uropod at the cell rear. Our interest was in studying the involvement of ion channels in the migration of activated human T lymphocytes as they modulate intracellular Ca2+ levels. Ca2+ is a key regulator of cellular motility. To this purpose, we created protein surfaces made of the bio-polymer PNMP and coated with ICAM-1, ligand of LFA-1. The LFA-1 and ICAM-1 interaction facilitates T cell movement from blood into tissues and it is critical in immune surveillance and inflammation. Activated human T lymphocytes polarized and migrated on ICAM-1 surfaces by random walk with a mean velocity of ∼6 µm/min. Confocal microscopy indicated that Kv1.3, CRAC, and TRPM4 channels positioned in the leading-edge, whereas KCa3.1 and TRPM7 channels accumulated in the uropod. The localization of KCa3.1 and TRPM7 at the uropod was associated with oscillations in intracellular Ca2+ levels that we measured in this cell compartment. Further studies with blockers against Kv1.3 (ShK), KCa3.1 (TRAM-34), CRAC (SKF-96365), TRPM7 (2-APB), and TRPM4 (glibenclamide) indicated that blockade of KCa3.1 and TRPM7, and not Kv1.3, CRAC or TRPM4, inhibits the T cell migration. The involvement of TRPM7 in cell migration was confirmed with siRNAs against TRPM7. Downregulation of TRPM7 significantly reduced the number of migrating T cells and the mean velocity of the migrating T cells. These results indicate that KCa3.1 and TRPM7 selectively localize at the uropod of migrating T lymphocytes and are key components of the T cell migration machinery.

Tiny Medicine: Nanomaterial-Based Biosensors

Tiny medicine refers to the development of small easy to use devices that can help in the early diagnosis and treatment of disease. Early diagnosis is the key to successfully treating many diseases. Nanomaterial-based biosensors utilize the unique properties of biological and physical nanomaterials to recognize a target molecule and effect transduction of an electronic signal. In general, the advantages of nanomaterial-based biosensors are fast response, small size, high sensitivity, and portability compared to existing large electrodes and sensors. Systems integration is the core technology that enables tiny medicine. Integration of nanomaterials, microfluidics, automatic samplers, and transduction devices on a single chip provides many advantages for point of care devices such as biosensors. Biosensors are also being used as new analytical tools to study medicine. Thus this paper reviews how nanomaterials can be used to build biosensors and how these biosensors can help now and in the future to detect disease and monitor therapies.

Surface Modification of a Biodegradable Magnesium Alloy with Phosphorylcholine (PC) and Sulfobetaine (SB) Functional Macromolecules for Reduced Thrombogenicity and Acute Corrosion Resistance

Siloxane functionalized phosphorylcholine (PC) or sulfobetaine (SB) macromolecules (PCSSi or SBSSi) were synthesized to act as surface modifying agents for degradable metallic surfaces to improve acute blood compatibility and slow initial corrosion rates. The macromolecules were synthesized using a thiol-ene radical photopolymerization technique and then utilized to modify magnesium (Mg) alloy (AZ31) surfaces via an anhydrous phase deposition of the silane functional groups. X-ray photoelectron spectroscopy surface analysis results indicated successful surface modification based on increased nitrogen and phosphorus or sulfur composition on the modified surfaces relative to unmodified AZ31. In vitro acute thrombogenicity assessment after ovine blood contact with the PCSSi and SBSSi modified surfaces showed a significant decrease in platelet deposition and bulk phase platelet activation compared with the control alloy surfaces. Potentiodynamic polarization and electrochemical impedance spectroscopy data obtained from electrochemical corrosion testing demonstrated increased corrosion resistance for PCSSi- and SBSSi-modified AZ31 versus unmodified surfaces. The developed coating technique using PCSSi or SBSSi showed promise in acutely reducing both the corrosion and thrombotic processes, which would be attractive for application to blood contacting devices, such as vascular stents, made from degradable Mg alloys.

Effect of biologically relevant ions on the corrosion products formed on alloy AZ31B: an improved understanding of magnesium corrosion.

Simulated physiological solutions mimicking human plasma have been utilized to study the in vitro corrosion of biodegradable metals. However, corrosion and corrosion product formation are different for different solutions with varied responses and, hence, the prediction of in vivo degradation behavior is not feasible based on these studies alone. This paper reports the role of physiologically relevant salts and their concentrations on the corrosion behavior of a magnesium alloy (AZ31B) and subsequent corrosion production formation. Immersion tests were performed for three different concentrations of Ca(2+), HPO4(2-), HCO3(-) to identify the effect of each ion on the corrosion of AZ31B assessed at 1, 3 and 10 days. Time-lapse morphological characterization of the samples was performed using X-ray computed tomography and scanning electron microscopy. The chemical composition of the surface corrosion products was determined by electron dispersive X-ray spectroscopy and X-ray diffraction. The results show that: (1) calcium is not present in the corrosion product layer when only Cl(-) and OH(-) anions are available; (2) the presence of phosphate induces formation of a densely packed amorphous magnesium phosphate corrosion product layer when HPO4(2-) and Cl(-) are present in solution; (3) octacalcium phosphate and hydroxyapatite (HAp) are deposited on the surface of the magnesium alloy when HPO4(2-) and Ca(2+) are present together in NaCl solution (this coating limits localized corrosion and increases general corrosion resistance); (4) addition of HCO3(-) accelerates the overall corrosion rate, which increases with increasing bicarbonate concentration; (5) the corrosion rate decreases due to the formation of insoluble HAp on the surface when HCO3(-), Ca(2+), and HPO4(2-) are present together.

Flow-induced corrosion behavior of absorbable magnesium-based stents.

The aim of this work was to study corrosion behavior of magnesium (Mg) alloys (MgZnCa plates and AZ31 stents) under varied fluid flow conditions representative of the vascular environment. Experiments revealed that fluid hydrodynamics, fluid flow velocity and shear stress play essential roles in the corrosion behavior of absorbable magnesium-based stent devices. Flow-induced shear stress (FISS) accelerates the overall corrosion (including localized, uniform, pitting and erosion corrosions) due to the increased mass transfer and mechanical force. FISS increased the average uniform corrosion rate, the localized corrosion coverage ratios and depths and the removal rate of corrosion products inside the corrosion pits. For MgZnCa plates, an increase of FISS results in an increased pitting factor but saturates at an FISS of ∼0.15Pa. For AZ31 stents, the volume loss ratio (31%) at 0.056Pa was nearly twice that (17%) at 0Pa before and after corrosion. Flow direction has a significant impact on corrosion behavior as more severe pitting and erosion corrosion was observed on the back ends of the MgZnCa plates, and the corrosion product layer facing the flow direction peeled off from the AZ31 stent struts. This study demonstrates that flow-induced corrosion needs be understood so that Mg-based stents in vascular environments can be effectively designed.