Thermosensitive hydrogels to deliver reactive species generated by cold atmospheric plasma: a case study with methylcellulose.

Hydrogels have been recently proposed as suitable materials to generate reactive oxygen and nitrogen species (RONS) upon gas-plasma treatment, and postulated as promising alternatives to conventional cancer therapies. Acting as delivery vehicles that allow a controlled release of RONS to the diseased site, plasma-treated hydrogels can overcome some of the limitations presented by plasma-treated liquids in in vivo therapies. In this work, we optimized the composition of a methylcellulose (MC) hydrogel to confer it with the ability to form a gel at physiological temperatures while remaining in the liquid phase at room temperature to allow gas-plasma treatment with suitable formation of plasma-generated RONS. MC hydrogels demonstrated the capacity for generation, prolonged storage and release of RONS. This release induced cytotoxic effects on the osteosarcoma cancer cell line MG-63, reducing its cell viability in a dose-response manner. These promising results postulate plasma-treated thermosensitive hydrogels as good candidates to provide local anticancer therapies.

Hydrothermal processing of 3D-printed calcium phosphate scaffolds enhances bone formation in vivo: a comparison with biomimetic treatment.

Hydrothermal (H) processes accelerate the hydrolysis reaction of α-tricalcium phosphate (α-TCP) compared to the long-established biomimetic (B) treatments. They are of special interest for patient-specific 3D-printed bone graft substitutes, where the manufacturing time represents a critical constraint. Altering the reaction conditions has implications for the physicochemical properties of the reaction product. However, the impact of the changes produced by the hydrothermal reaction on the in vivo performance was hitherto unknown. The present study compares the bone regeneration potential of 3D-printed α-TCP scaffolds hardened using these two treatments in rabbit condyle monocortical defects. Although both consolidation processes resulted in biocompatible scaffolds with osseointegrative and osteoconductive properties, the amount of newly formed bone increased by one third in the hydrothermal vs the biomimetic samples. B and H scaffolds consisted mostly of high specific surface area calcium-deficient hydroxyapatite (38 and 27 m2 g-1, respectively), with H samples containing also 10 wt.% ß-tricalcium phosphate (ß-TCP). The shrinkage produced during the consolidation process was shown to be very small in both cases, below 3%, and smaller for H than for B samples. The differences in the in vivo performance were mainly attributed to the distinct crystallisation nanostructures, which proved to have a major impact on permeability and protein adsorption capacity, using BSA as a model protein, with B samples being highly impermeable. Given the crucial role that soluble proteins play in osteogenesis, this is proposed to be a relevant factor behind the distinct in vivo performances observed for the two materials. STATEMENT OF SIGNIFICANCE: The possibility to accelerate the consolidation of self-setting calcium phosphate inks through hydrothermal treatments has aroused great interest due to the associated advantages for the development of 3D-printed personalised bone scaffolds. Understanding the implications of this approach on the in vivo performance of the scaffolds is of paramount importance. This study compares, for the first time, this treatment to the long-established biomimetic setting strategy in terms of osteogenic potential in vivo in a rabbit model, and relates the results obtained to the physicochemical properties of the 3D-printed scaffolds (composition, crystallinity, nanostructure, nanoporosity) and their interaction with soluble proteins.

Osteosarcoma tissue-engineered model challenges oxidative stress therapy revealing promoted cancer stem cell properties.

The use of oxidative stress generated by Cold Atmospheric Plasma (CAP) in oncology is being recently studied as a novel potential anti-cancer therapy. However, the beneficial effects of CAP for treating osteosarcoma have mostly been demonstrated in 2-dimensional cultures of cells, which do not mimic the complexity of the 3-dimensional (3D) bone microenvironment. In order to evaluate the effects of CAP in a relevant context of the human disease, we developed a 3D tissue-engineered model of osteosarcoma using a bone-like scaffold made of collagen type I and hydroxyapatite nanoparticles. Human osteosarcoma cells cultured within the scaffold showed a high capacity to infiltrate and proliferate and to exhibit osteomimicry in vitro. As expected, we observed significantly different functional behaviors between monolayer and 3D cultures when treated with Cold Plasma-Activated Ringer's Solution (PAR). Our data reveal that the 3D environment not only protects cells from PAR-induced lethality by scavenging and diminishing the amount of reactive oxygen and nitrogen species generated by CAP, but also favours the stemness phenotype of osteosarcoma cells. This is the first study that demonstrates the negative effect of PAR on cancer stem-like cell subpopulations in a 3D biomimetic model of cancer. These findings will allow to suitably re-focus research on plasma-based therapies in future.

Plasma-Conditioned Liquids as Anticancer Therapies In Vivo: Current State and Future Directions.

Plasma-conditioned liquids (PCL) are gaining increasing attention in the medical field, especially in oncology, and translation to the clinics is advancing on a good path. This emerging technology involving cold plasmas has great potential as a therapeutic approach in cancer diseases, as PCL have been shown to selectively kill cancer cells by triggering apoptotic mechanisms without damaging healthy cells. In this context, PCL can be injected near the tumor or intratumorally, thereby allowing the treatment of malignant tumors located in internal organs that are not accessible for direct cold atmospheric plasma (CAP) treatment. Therefore, PCL constitutes a very interesting and minimally invasive alternative to direct CAP treatment in cancer therapy, avoiding surgeries and allowing multiple local administrations. As the field advances, it is progressively moving to the evaluation of the therapeutic effects of PCL in in vivo scenarios. Exciting developments are pushing forward the clinical translation of this novel therapy. However, there is still room for research, as the quantification and identification of reactive oxygen and nitrogen species (RONS) in in vivo conditions is not yet clarified, dosage regimens are highly variable among studies, and other more relevant in vivo models could be used. In this context, this work aims to present a critical review of the state of the field of PCL as anticancer agents applied in in vivo studies.

Magnetoelectrically Driven Catalytic Degradation of Organics.

Here, the catalytic degradation of organic compounds is reported by exploiting the magnetoelectric nature of cobalt ferrite-bismuth ferrite (CFO-BFO) core-shell nanoparticles. The combination of magnetostrictive CFO with multiferroic BFO gives rise to a magnetoelectric engine that purifies water under wireless magnetic fields via advanced oxidation processes, without involvement of any sacrificial molecules or cocatalysts. Magnetostrictive CoFe2 O4 nanoparticles are fabricated using hydrothermal synthesis, followed by sol-gel synthesis to create the multiferroic BiFeO3 shell. Theoretical modeling is performed to study the magnetic-field-induced polarization on the surface of magnetoelectric nanoparticles. The results obtained from these simulations are consistent with experimental findings of the piezoforce microscopy analysis, where changes in piezoresponse of the nanoparticles under magnetic fields are observed. Next, the magnetoelectric-effect-induced catalytic degradation of organic pollutants is investigated under AC magnetic fields, and 97% removal efficiency for synthetic dyes and over 85% removal efficiency for routinely used pharmaceuticals are obtained. Additionally, trapping experiments are performed to elucidate the mechanism behind the magnetic-field-induced catalytic degradation of organic pollutants by using scavengers for each of the reactive species. The results indicate that hydroxyl and superoxide radicals are the main reactive species in the magnetoelectrically induced catalytic degradation of organic compounds.

A contactless positioning system for monitoring discontinuities in three dimensions with geological and geotechnical applications.

In this paper, a contactless positioning system is presented which has been designed to monitor the kinematic behavior of mechanical discontinuities in three dimensions. The positioning system comprises a neodymium magnet, fixed on one side of a discontinuity, and a magnetoresistive sensing array, fixed on the opposing side. Each of the anisotropic magnetoresistive sensors in the sensing array records the magnetic field along three orthogonal directions. The positioning system intrinsically generates compact data packages which are transmitted effectively using a range of standard wireless telecommunication technologies. These data are then modeled using a global least squares fitting procedure in which the adjustable parameters are represented by the position and orientation of the neodymium magnet. The instrumental resolution of the positioning system can be tuned depending on the strength of the magnetic field generated by the neodymium magnet and the distance between the neodymium magnet and the magnetoresistive sensing array. For a typical installation, the displacement resolution is shown to be circa 10 µm while the rotation resolution is circa 0.1°. The first permanently deployed positioning system was established in June 2016 to monitor the behavior of an N-S trending fault located at the contact between the eastern Alps and the Vienna Basin. The robust design of the positioning system is demonstrated by the fact that no interruptions in the broadcasted data streams have occurred since its installation. It has a range of potential applications in many areas of basic and applied research including geology, geotechnical engineering, and structural health monitoring.

On the persistence of polar domains in ultrathin ferroelectric capacitors.

The instability of ferroelectric ordering in ultra-thin films is one of the most important fundamental issues pertaining realization of a number of electronic devices with enhanced functionality, such as ferroelectric and multiferroic tunnel junctions or ferroelectric field effect transistors. In this paper, we investigate the polarization state of archetypal ultrathin (several nanometres) ferroelectric heterostructures: epitaxial single-crystalline BaTiO3 films sandwiched between the most habitual perovskite electrodes, SrRuO3, on top of the most used perovskite substrate, SrTiO3. We use a combination of piezoresponse force microscopy, dielectric measurements and structural characterization to provide conclusive evidence for the ferroelectric nature of the relaxed polarization state in ultrathin BaTiO3 capacitors. We show that even the high screening efficiency of SrRuO3 electrodes is still insufficient to stabilize polarization in SrRuO3/BaTiO3/SrRuO3 heterostructures at room temperature. We identify the key role of domain wall motion in determining the macroscopic electrical properties of ultrathin capacitors and discuss their dielectric response in the light of the recent interest in negative capacitance behaviour.

Calculating flux to predict future cave radon concentrations.

Cave radon concentration measurements reflect the outcome of a perpetual competition which pitches flux against ventilation and radioactive decay. The mass balance equations used to model changes in radon concentration through time routinely treat flux as a constant. This mathematical simplification is acceptable as a first order approximation despite the fact that it sidesteps an intrinsic geological problem: the majority of radon entering a cavity is exhaled as a result of advection along crustal discontinuities whose motions are inhomogeneous in both time and space. In this paper the dynamic nature of flux is investigated and the results are used to predict cave radon concentration for successive iterations. The first part of our numerical modelling procedure focuses on calculating cave air flow velocity while the second part isolates flux in a mass balance equation to simulate real time dependence among the variables. It is then possible to use this information to deliver an expression for computing cave radon concentration for successive iterations. The dynamic variables in the numerical model are represented by the outer temperature, the inner temperature, and the radon concentration while the static variables are represented by the radioactive decay constant and a range of parameters related to geometry of the cavity. Input data were recorded at Driny Cave in the Little Carpathians Mountains of western Slovakia. Here the cave passages have developed along splays of the NE-SW striking Smolenice Fault and a series of transverse faults striking NW-SE. Independent experimental observations of fault slip are provided by three permanently installed mechanical extensometers. Our numerical modelling has revealed four important flux anomalies between January 2010 and August 2011. Each of these flux anomalies was preceded by conspicuous fault slip anomalies. The mathematical procedure outlined in this paper will help to improve our understanding of radon migration along crustal discontinuities and its subsequent exhalation into the atmosphere. Furthermore, as it is possible to supply the model with continuous data, future research will focus on establishing a series of underground monitoring sites with the aim of generating the first real time global radon flux maps.

The instrumental resolution of a moire extensometer in light of its recent automatisation.

This paper assesses the instrumental resolution of a mechanical extensometer in light of its recent automatisation. The instrument takes advantage of the moire phenomenon of optical interference to measure angular rotation in two perpendicular planes and displacement in three dimensions. Our assessment systematically defines an analytical solution for the complete interpretation of a generic moire pattern and a set of mathematical approximations for the moire patterns used to measure rotation and displacement. The ultimate sensitivity of the automated instrument is determined on the basis of a generic least square differences fitting procedure while the instrumental resolution is defined on the basis of realistic, rather than optimal, scenarios: the resolution of the rotation measurements are in the order of 8.7*10-5 rad while the resolution of the displacement measurements are better than 5 µm. This assessment represents the first step towards a global numerical repository for processed data recorded by the automated extensometers.

Four-state ferroelectric spin-valve.

Spin-valves had empowered the giant magnetoresistance (GMR) devices to have memory. The insertion of thin antiferromagnetic (AFM) films allowed two stable magnetic field-induced switchable resistance states persisting in remanence. In this letter, we show that, without the deliberate introduction of such an AFM layer, this functionality is transferred to multiferroic tunnel junctions (MFTJ) allowing us to create a four-state resistive memory device. We observed that the ferroelectric/ferromagnetic interface plays a crucial role in the stabilization of the exchange bias, which ultimately leads to four robust electro tunnel electro resistance (TER) and tunnel magneto resistance (TMR) states in the junction.

Multisegmented FeCo/Cu nanowires: electrosynthesis, characterization, and magnetic control of biomolecule desorption.

In this paper, we report on the synthesis of FeCo/Cu multisegmented nanowires by means of pulse electrodeposition in nanoporous anodic aluminum oxide arrays supported on silicon chips. By adjustment of the electrodeposition conditions, such as the pulse scheme and the electrolyte, alternating segments of Cu and ferromagnetic FeCo alloy can be fabricated. The segments can be built with a wide range of lengths (15-150 nm) and exhibit a close-to-pure composition (Cu or FeCo alloy) as suggested by energy-dispersive X-ray mapping results. The morphology and the crystallographic structure of different nanowire configurations have been assessed thoroughly, concluding that Fe, Co, and Cu form solid solution. Magnetic characterization using vibrating sample magnetometry and magnetic force microscopy reveals that by introduction of nonmagnetic Cu segments within the nanowire architecture, the magnetic easy axis can be modified and the reduced remanence can be tuned to the desired values. The experimental results are in agreement with the provided simulations. Furthermore, the influence of nanowire magnetic architecture on the magnetically triggered protein desorption is evaluated for three types of nanowires: Cu, FeCo, and multisegmented FeCo15nm/Cu15nm. The application of an external magnetic field can be used to enhance the release of proteins on demand. For fully magnetic FeCo nanowires the applied oscillating field increased protein release by 83%, whereas this was found to be 45% for multisegmented FeCo15nm/Cu15nm nanowires. Our work suggests that a combination of arrays of nanowires with different magnetic configurations could be used to generate complex substance concentration gradients or control delivery of multiple drugs and macromolecules.

Giant reversible nanoscale piezoresistance at room temperature in Sr2IrO4 thin films.

Layered iridates have been the subject of intense scrutiny on account of their unusually strong spin-orbit coupling, which opens up a narrow bandgap in a material that would otherwise be a metal. This insulating state is very sensitive to external perturbations. Here, we show that vertical compression at the nanoscale, delivered using the tip of a standard scanning probe microscope, is capable of inducing a five orders of magnitude change in the room temperature resistivity of Sr2IrO4. The extreme sensitivity of the electronic structure to anisotropic deformations opens up a new angle of interest on this material, with the giant and fully reversible perpendicular piezoresistance rendering iridates as promising materials for room temperature piezotronic devices.

Spintronic functionality of BiFeO3 domain walls.

Anisotropic magnetoresistance at the BiFeO3 domain walls has been observed thanks to the realization of micro-devices that allow the direct magneto-transport characterization of the domain-walls. Anisotropic magnetoresistance of ferromagnetic metals has been a pillar in spintronic technology, and now it is evidenced at the conductive domain walls of an insulating ferroelectric material, which implies that domain walls become an electrically tunable nanospintronic object.

Room-temperature negative capacitance in a ferroelectric-dielectric superlattice heterostructure.

We demonstrate room-temperature negative capacitance in a ferroelectric-dielectric superlattice heterostructure. In epitaxially grown superlattice of ferroelectric BSTO (Ba0.8Sr0.2TiO3) and dielectric LAO (LaAlO3), capacitance was found to be larger compared to the constituent LAO (dielectric) capacitance. This enhancement of capacitance in a series combination of two capacitors indicates that the ferroelectric was stabilized in a state of negative capacitance. Negative capacitance was observed for superlattices grown on three different substrates (SrTiO3 (001), DyScO3 (110), and GdScO3 (110)) covering a large range of substrate strain. This demonstrates the robustness of the effect as well as potential for controlling the negative capacitance effect using epitaxial strain. Room-temperature demonstration of negative capacitance is an important step toward lowering the subthreshold swing in a transistor below the intrinsic thermodynamic limit of 60 mV/decade and thereby improving energy efficiency.

Skin layer of BiFeO(3) single crystals.

A surface layer ("skin") different from the bulk was found in single crystals of BiFeO(3). Impedance analysis and grazing incidence x-ray diffraction reveal a phase transition at T(*)∼275±5 °C that is confined within the surface of BiFeO(3). X-ray photoelectron spectroscopy and refraction-corrected x-ray diffraction as a function of incidence angle and photon wavelength indicate a reduced electron density and an elongated out-of-plane lattice parameter within a few nanometers of the surface. The skin will affect samples with large surface to volume ratios, as well as devices that rely on interfacial coupling such as exchange bias.