The development of bioresorbable Fe-Mn alloys for orthopedic implantation

Bioresorbable metals have immense potential to be used in the clinical treatment of a variety of soft and hard tissue injuries and disease. For many applications, the presence of a permanent device may cause severe negative effects and require re-intervention in the long-term. A transient support for a healing tissue is an attractive solution for orthopaedic and vascular interventions alike. For applications in bone fracture in particular, the human body requires fixation devices to support bone regrowth in the proper alignment, but only for a short period of time (typically 6-12 months). We aim to design bioresorbable materials to fill this gap in the current offerings of implants. One such material system with promising results is iron-manganese (Fe-Mn) alloys. Our goal is to tailor the material’s corrosion rate, mechanical properties, and cellular interactions to support tissue healing and remodeling. Here, we characterized the surface evolution and degradation kinetics of Fe-20%Mn while immersed in osteogenic media for 90 days. It was found that the thick, quickly-forming Fe-rich oxide layer that forms on the surface severely inhibits the degradation rate of the alloy. Comparisons were drawn between the degradation rates obtained from immersion mass loss testing and electrochemical experiments. Electrochemical experiments clearly overestimate the true degradation rate of the alloy in vitro, but quick evaluations can be made between materials processed differently. The composition of the alloy, final microstructure, and manufacturing method employed to create the implant were found to affect the structure of the rapidly formed, iron-rich oxide layer, which inherently affects the amount of ion release from the alloy while immersed in biological environments. In an attempt to enhance the degradation rate, we then used large-strain machining (LSM), a novel severe plastic deformation (SPD) technique was utilized during these experiments to modify the degradation properties of a Fe-33%Mn alloy. It was discovered that Fe-33%Mn after LSM with a rake angle of α=0º (effective strain=2.85) showed the most promising increase in degradation rate compared to as-cast, annealed, and additional deformation conditions (rolled and other LSM parameters) for the same alloy. It was discovered that to increase the degradation rate further for Fe–Mn alloys, (1) tailored shear-based deformation processing can increase the kinetic effects of corrosion up to a critical value, (2) the surface area of the implants should be increased to allow for more diffusion of the osteogenic media into the Fe–Mn bulk alloy, which would also provide more adhesion and ingrowth of the hard tissue environment, or (3) new elements or components should be added to the alloy to facilitate increased degradation. Another step of the research involved the use of dealloying on Fe-30%Mn alloys to selectively leach out diffused Zn and create tailorable, nanoporous structures to facilitate increased initial cell attachment and ingrowth. The mechanisms of dealloying were explored and the major factors found that affect the final surface structures include: (1) Initial microstructure, (2) Zn diffusion rate, (3) Etching/dealloying rate, (4) Temperature and time of annealing treatment, (5) etching with different acid or basic media. Continuing this concept over to a cell attachment study, 11 various topographical configurations of the dealloying treatment were chosen to investigate initial bone marrow stromal cell attachment and improve tissue/implant interface adhesion. Cells were attached over a period of 24 hours and an MTS Assay was used to measure cell viability. Comparing this data with fluorescence microscopy, SEM, and roughness values experimentally found through AFM, certain surfaces were found to be more conducive to attachment of cells

Bio‐Nanopatterning: Inkjet printed nanopatterned aptamer‐based sensors for improved optical detection of foodborne pathogens

The increasing incidence of infectious outbreaks from contaminated food and water supplies continues to impose a global burden for public health. There is a market demand for on‐site, disposable, easy‐to‐use, and cost‐efficient pathogen sensing devices. Despite the rapid growth of biosensing as a research field, and the generation of breakthrough technologies, more than 80% of the biosensors developed at the laboratory scale never will get to meet the market. This work presents a cost‐efficient, reliable, and repeatable aptasensing platform for the whole-cell detection of foodborne pathogens in real food samples. An optimized inkjet printing platform was designed, taking advantage of the carefully controlled bionanopatterning of novel carboxyl‐functionalized aptameric inks on a nitrocellulose substrate. Please click Additional Files below to see the full abstract

Electrochemical Sensing with Metal Oxides

The effective sensing of hydrogen peroxide is important for a variety of reasons. It can be utilized as a diagnostic tool for diseases like asthma; also, the sensing can be utilized in pharmaceutical and food production for quality control. The use of silver oxide nanoparticles with varying morphologies has not been investigated as a sensing agent for hydrogen peroxide in the past. The particles’ properties and ability to oxidize and reduce hydrogen peroxide suggest that they will be effective to create a sensitive sensor. The silver oxide particles were prepared through chemical reduction using varying molar ratios of reactants. The varying ratios created three different particle shapes: hexapod, octahedral, and cubic. A three electrode system was to evaluate electrochemical properties, and the working electrode was coated with the silver oxide particles. Current response, detection limit, and electrical impedance spectroscopy (EIS) tests were done to gauge the effectiveness of the sensor, and X-ray diffraction (XRD), Zeta potential, and scanning electron microscopy (SEM) were performed to characterize the particles. The use of these particles has shown positive results for a sensor, with very high sensitivity and a good detection limit. The hexapods gave more response than the octahedral which gave more response than the cubic particles. The low stability suggests a new coating method must be investigated, but overall, the very high sensitivity of the silver oxide particles would be useful for aforementioned applications of hydrogen peroxide sensing

The Role of Metal Oxide Layers in the Sensitivity of Lactate Biosensors Subjected to Oxygen-Limited Conditions

Amperometric lactate biosensors are used to detect lactate concentration in blood and tissues, which is integral in identifying cyanide poisoning, septic shock, and athletic condition. The construction of lactate biosensors with high sensitivity, selectivity, and stability is imperative to diagnose and determine these medical conditions. Lactate detection is currently limited to oxygen-rich environments due to the fact that oxygen is a limiting factor in the lactate reaction. To circumvent this problem, researchers have developed mediators or alternate, oxygen-free enzymes to improve sensitivity. In our study, ceria (CeO2) with high oxygen storage capacity (OSC) was introduced to the enzyme layer to eliminate the effects of oxygen depletion. Fluctuation in oxygen concentration was combatted by use of ceria metal oxide nanopowders, which absorb and release oxygen under oxygen rich and lean conditions respectively. These nanopowders were deposited on the electrode surface in a polyelectrolyte solution. The lactate biosensors were then constructed using layer-by-layer assembly to take advantage of electrostatic interaction between the positively charged polyelectrolyte and negatively charged lactate oxidase (LOx). Polyethylenimine (PEI), a positively charged polymer, was used to immobilize the enzymes on the Pt surface via alternating electrostatic adsorption. It was observed that the introduction of ceria in the enzyme layer reduced oxygen dependency. The results showed that lactate biosensors with high selectivity, sensitivity, and wide detection limit were constructed

Investigation of the Interaction between Nafion Ionomer and Surface Functionalized Carbon Black Using Both Ultrasmall Angle X-ray Scattering and Cryo-TEM

In making a catalyst ink, the interactions between Nafion ionomer and catalyst support are the key factors that directly affect both ionic conductivity and electronic conductivity of the catalyst layer in a membrane electrode assembly. One of the major aims of this investigation is to understand the behavior of the catalyst support, Vulcan XC-72 (XC-72) aggregates, in the existence of the Nafion ionomer in a catalyst ink to fill the knowledge gap of the interaction of these components. The dispersion of catalyst ink depends not only on the solvent but also on the interaction of Nafion and carbon particles in the ink. The interaction of Nafion ionomer particles and XC-72 catalyst aggregates in liquid media was studied using ultrasmall-angle X-ray scattering and cryogenic TEM techniques. Carbon black (XC-72) and functionalized carbon black systems were introduced to study the interaction behaviors. A multiple curve fitting was used to extract the particle size and size distribution from scattering data. The results suggest that the particle size and size distribution of each system changed significantly in Nafion + XC-72 system, Nafion + NH2-XC72 system, and Nafion + SO3H-XC-72 system, which indicates that an interaction among these components (i.e., ionomer particles and XC-72 aggregates) exists. The cryogenic TEM, which allows for the observation the size of particles in a liquid, was used to validate the scattering results and shows excellent agreement

In-vivo evaluation of biocompatibility of biodegradable Fe-Mn materials

The authors evaluated the biodegradability and biocompatibility of an alloy of iron and manganese in a bone model in vivo. Fe-Mn biodegradable materials with various porosities were first fabricated and characterized for microstructure, corrosion and mechanical properties. Resorption of a bioabsorbable wire of chemical formula Fe30Mn and no induced porosity was evaluated in-vivo. The Fe-Mn alloy behavior in-vivo was compared to that of a traditional permanent 316L stainless steel (SS) wire after bilateral transcondylar femoral implantation in 12 rats. Evaluation of biodegradation was performed over a period of 6 months using serial radiography, post-mortem histology and macroscopic implant surface analysis. Increased bone ingrowth was noted at the iron-manganese wire-bone interface, which indicates increased osseointegration of the implant. Please click Additional Files below to see the full abstract

Polybenzimidazole (PBI) Functionalized Nanographene as Highly Stable Catalyst Support for Polymer Electrolyte Membrane Fuel Cells (PEMFCs)

Nanoscale graphenes were used as cathode catalyst supports in proton exchange membrane fuel cells (PEMFCs). Surface-initiated polymerization that covalently bonds polybenzimidazole (PBI) polymer on the surface of graphene supports enables the uniform distribution of the Pt nanoparticles, as well as allows the sealing of the unterminated carbon bonds usually present on the edge of graphene from the chemical reduction of graphene oxide. The nanographene effectively shortens the length of channels and pores for O2 diffusion/water dissipation and significantly increases the primary pore volume. Further addition of p-phenyl sulfonic functional graphitic carbon particles as spacers, increases the specific volume of the secondary pores and greatly improves O2 mass transport within the catalyst layers. The developed composite cathode catalyst of Pt/PBI-nanographene (50 wt%) + SO3H-graphitic carbon black demonstrates a higher beginning of life (BOL) PEMFC performance as compared to both Pt/PBI-nanographene (50 wt%) and Pt/PBI-graphene (50 wt%) + SO3H-graphitic carbon black (GCB). Accelerated stress tests show excellent support durability compared to that of traditional Pt/Vulcan XC72 catalysts, when subjected to 10,000 cycles from 1.0 V to 1.5 V. This study suggests the promise of using PBI-nanographene + SO3H-GCB hybrid supports in fuel cells to achieve the 2020 DOE targets for transportation applications

Two C-terminal Sequence Variations Determine Differential Neurotoxicity Between Human and Mouse α-synuclein

BACKGROUND: α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson\u27s disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology. METHODS: Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. Brain sections prepared from rats injected intranigrally with aSyn-encoding adeno-associated viruses were analyzed immunohistochemically to determine nigral dopaminergic neuron viability and striatal dopaminergic terminal density. Recombinant aSyn variants were characterized in terms of fibrillization rates by measuring thioflavin T fluorescence, fibril morphologies via electron microscopy and atomic force microscopy, and protein-lipid interactions by monitoring membrane-induced aSyn aggregation and aSyn-mediated vesicle disruption. Statistical tests consisted of ANOVA followed by Tukey\u27s multiple comparisons post hoc test and the Kruskal-Wallis test followed by a Dunn\u27s multiple comparisons test or a two-tailed Mann-Whitney test. RESULTS: Mouse aSyn was less neurotoxic than human aSyn A53T in cell culture and in rat midbrain, and data obtained for the chimeric variants indicated that the human-to-mouse substitutions D121G and N122S were at least partially responsible for this decrease in neurotoxicity. Human aSyn A53T and a chimeric variant with the human residues D and N at positions 121 and 122 (respectively) showed a greater propensity to undergo membrane-induced aggregation and to elicit vesicle disruption. Differences in neurotoxicity among the human, mouse, and chimeric aSyn variants correlated weakly with differences in fibrillization rate or fibril morphology. CONCLUSIONS: Mouse aSyn is less neurotoxic than the human A53T variant as a result of inhibitory effects of two C-terminal amino acid substitutions on membrane-induced aSyn aggregation and aSyn-mediated vesicle permeabilization. Our findings highlight the importance of membrane-induced self-assembly in aSyn neurotoxicity and suggest that inhibiting this process by targeting the C-terminal domain could slow neurodegeneration in PD and other synucleinopathy disorders