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3D bioprinted cardiac patches are biomaterial free

Advances in medical imaging enable bespoke tissues and organs to be developed for transplant or engraftment with remarkable resolution and definition using 3D bioprinting. The incorporation of stem cell therapies into these 3D tissue constructs is incredibly promising for the delivery of pioneering stem cell regenerative therapies. Typically, 3D bioprinting requires use of a biomaterial to aid with deposition, which can cause negative host responses. To avoid such problems, US researchers have developed a biomaterial-free cardiac patch (Scientific Reports 7 4566).

Developing a biomaterial-free cardiac patch

Heart disease affects thousands of people every year and effective repair of cardiac tissue would reduce a large medical health care burden. Researchers from the Narutoshi Hibino labat Johns Hopkins Hospital and Johns Hopkins University have devised a 3D-bioprinting procedure that allows for the biofabrication of cardiac tissue patches to deliver regenerative stem cells, without using biomaterials. The process utilises aggregated balls of cardiac cells (cardiospheroids), which are directly printed into a cardiac patch construct. The cardiospheroids are identified, picked up by a vacuum and bioprinted directly onto a needle microarray (a video of the 3D-bioprinting process used is available from JOVE). This novel method allows the patch to be constructed with cells alone and will avoid detrimental effects induced by biomaterial grafts.

Stem cell techniques for tissue regeneration typically rely on biomaterial scaffolds to provide structure and support for cells during grafting. The grafting or introduction of biomaterials to a patient induces an immune response, or can create scar tissue from the graft, potentially damaging the region of tissue intended to be repaired. Through developing a biomaterial-free graft, it is possible to avoid these detrimental factors. And by using a patient’s own stem cells it is possible to create native tissue that is fully biocompatible.

Cardiac patch integrity

3D bioprinting was crucial to the development of effective cardiac patches, with specific spatial distribution being crucial to mechanical integrity. Cardiospheres without specific placement to overlap with other cardiospheres disintegrated after removal from the needle array; although partially disintegrated regions were able to fuse back together eventually. This effect removed the structural definition of the patch, negating the advantages of using bioprinting for developing a cardiac patch of specified dimensions.

In vivo grafts

The researchers grafted patches onto rat hearts and after a week saw signs of blood vessel formation, with viable cells and red blood cells present in the cardiac patch. Tissue protein stains showed that collagen was present in the patch, indicating the deposition of a native extracellular matrix from the cells, crucial to cell integration. Further staining showed the presence of human nucleic acid in rat tissue, implying that the human cell derived patch had successfully grafted with the rat tissue.

This biomaterial-free cardiac patch was developed using pluripotent cardiomyocyte stem cells, cardiac fibroblasts and human umbilical vein endothelial cells (HUVECs), which were aggregated into cardiospheroids for bioprinting. Cardiospheroids were able to develop a functional phenotype after 48 hours, with spontaneous beating and electrical conductivity a week after bioprinting. Cardiomyocytes alone were not able to reproduce this functional phenotype.

Biomaterial-free future?

This process demonstrates a novel approach to eliminating biomaterial-induced damage. Further development of this 3D bioprinting technique in conjunction with stem cell therapies could progress biomaterial-free cardiac patches into the popular domain.

Cassini provides a magnetic mystery

Saturn’s magnetic field has no discernible tilt relative to the planet’s rotational axis, according to data from NASA’s Cassini spacecraft. This unexpected result means the exact length of a day on the planet is still unknown.

Cassini is currently undergoing its Grand Finale phase – 22 weekly orbits of Saturn that take the spacecraft between the planet and its rings. This stage of the Cassini’s mission began on 26 April and it has completed 14 of the orbits. After 22, Cassini will perform its final act and plummet into the planet’s atmosphere on September 15.

Aligned and challenging

Among the vast swathes of data sent back by Cassini, the spacecraft’s magnetometer instrument has revealed that Saturn’s magnetic field is closely aligned to its rotational axis. The tilt is in fact much smaller than the lower limit (0.06°) the magnetometer data indicated before the Grand Finale.

The observation challenges the current understanding of how a planet generates a magnetic field. It is thought that there must be some degree of tilt to sustain currents flowing through liquid metal within the planet. Without a tilt, the currents should subside, causing the magnetic field to disappear.

Unknown day

The result also means the true length of a day on Saturn is unknown, because it is measured by a daily “wobble” in the planet’s interior caused by the misalignment of magnetic field and rotational axis. “We have not been able to resolve the length of day at Saturn so far, but we’re still working on it,” says Michele Dougherty, Cassini magnetometer investigation lead from Imperial College London in the UK.

There is the possibility, however, that the lack of tilt may be rectified with further data. Dougherty and colleagues believe an aspect of Saturn’s atmosphere could be masking the true magnetic fields and Cassini’s plunge into Saturn may reveal further clues.

Spinning black holes could grow long hair

A potentially explosive phenomenon called superradiance could give black holes hair – according to William East of the Perimeter Institute for Theoretical Physics in Canada and Frans Pretorius of Princeton University in the US. Their claim relies on the existence of an extremely light particle and could be confirmed by detecting gravitational waves associated with the hair.

Black holes famously have “no hair”. This is the conventional idea that a black hole can only be described in terms of three quantities: mass, angular momentum and charge. All other physical properties (the hair) of the stuff that has been sucked into a black hole are lost forever. Evidence for the no-hair theorem has been seen by LIGO, which has detected the gravitational waves produced when two black holes merge.

However, the idea of having no hair does not sit very well with basic principles of quantum mechanics and as a result, the possibility of black-hole hair is an active area of physics research.

Black-hole bomb

Another curious phenomenon associated with black holes is superradiance. This involves particles and electromagnetic radiation scattering from a spinning black hole and gaining energy and angular momentum in the process. If this radiation is reflected back at the black hole, a runaway explosive process called a “black-hole bomb” could develop.

For this process to occur spontaneously there must exist a hitherto unknown boson particle and associated field. Furthermore, the mass of the boson must be extremely low – about 10–17 that of the electron. As a result, the observation of runaway superradiance in black holes could signal the existence of physics beyond the Standard Model of particle physics – perhaps providing an explanation of dark matter.

Quasistable state

Now, East and Pretorius have done detailed simulations of this process for a spinning solar-mass black hole with zero charge. They have found that rather than being explosively unstable, superradiance can settle into a quasistable state in which about 9% of the black-hole’s mass/energy is transferred to a field of hypothetical bosons that becomes trapped around the black hole.

This bosonic halo is called a “Proca cloud” and can be thought of as “long hair” that persists for a relatively long time and also extends out beyond the event horizon of the black hole. Black holes with such hair are expected to broadcast gravitational waves at a specific frequency – and in principle these could be detected by LIGO or perhaps the upcoming space-based LISA gravitational-wave detector.

The simulations are described in Physical Review Letters.

New 3D scanning method uses Archimedes’ principle

Scientists have used Archimedes’ ancient principle of water displacement to develop a new 3D scanning and reconstruction technique. The method was developed by an international team led by Kfir Aberman, Oren Katzir, Daniel Cohen-Or and colleagues at Tel-Aviv University in Israel, who have used it to successfully reconstruct complex objects including cavities.

Typically, 3D scanning and reconstruction methods use optical devices that probe the visible surface of an object. While these techniques are reasonably efficient, they cannot capture features of an object that are hidden from the optics’ line of sight. Conventional methods also struggle with glossy or transparent surfaces, which can result in noisy scans.

Archimedes approach

To overcome these limitations, Aberman, Katzir and colleagues took a different approach. Rather than relying on optics they turned to Archimedes’ principle, which states that “the volume of fluid displaced is equal to the volume of the part that was submerged.”

The technique uses a robotic arm to dip an object into a water tank along a controlled direction. As the object is submerged, the water displacement is measured, giving a thin volume slice of the shape. The researchers then repeat this process multiple times by dipping at different angles. Using mathematical models, they convert the volume slices into a dip transform – a 3D representation of the object.

Cat, octopus, elephant

The more often the object is dipped, the greater detail about its geometry can be extracted. Aberman, Katzir and colleagues were able to reconstruct a variety of complex sculptures, including a DNA-like helix, cats, an octopus and an elephant with a rider.

Although the technique does not require expensive equipment or customized environments, it assumes the object has no air pockets when dipped. The team is working on methods to overcome this limitation by measuring the level of water while the object is being vertically lifted out as well as dipped in. This may reveal further details about the object’s geometry.

The work will be presented at the 44th SIGGRAPH Conference on Computer Graphics and Interactive Techniques, which will be held in Los Angeles in the USA later this month.

UK commits £246m to developing battery technology

The UK government has launched the “Faraday Challenge”, which will invest £246m in boosting the country’s expertise in developing battery technology.

Running over four years, the first phase of the programme will include a competition to develop a £45m “Battery Institute” that will provide a framework for battery research and development. The institute will be a consortium of universities that will be selected by the Engineering and Physical Sciences Research Council, which provides government funding for research in the UK.

Promising research done by the Battery Institute and elsewhere in the UK will be moved towards commercialization through collaborations between academia and industry. This process will be facilitated by Innovate UK, which is a government body that provides funding to companies for the development of new products and services based on science and technology.

Manufacturing development

The Faraday Challenge will also fund a new National Battery Manufacturing Development Facility for the UK. A competition for hosting the facility will be led by the Advanced Propulsion Centre, which is an industry-led private company that seeks to develop technologies that can be used in low-carbon-emission transportation systems.

The Faraday Challenge was announced by business secretary Greg Clark, who has appointed Richard Parry-Jones to chair the Faraday Challenge Advisory Board. Parry-Jones spent much of his career working for the Ford Motor Company, where he held several senior positions before retiring a decade ago to work as an adviser to governments and industry.

Parry-Jones says: “The power of the Faraday Challenge derives from the joining-up of all three stages of research from the brilliant research in the university base, through innovation in commercial applications to scaling up for production.” He adds: “It will focus our best minds on the critical industrial challenges that are needed to establish the UK as one of the world leaders in advanced battery technologies and associated manufacturing capability.”

Work begins on US neutrino experiment

Construction has begun on a huge neutrino facility located at the Sanford Underground Research Facility in Lead, South Dakota. The Long-Baseline Neutrino Facility (LBNF) will study the properties of neutrinos in unprecedented detail, as well as the differences in behaviour between neutrinos and antineutrinos. Institutions in 30 countries are involved with the LBNF, which will take about a decade to build and once complete will be the world’s highest-intensity neutrino beam.

The centrepiece of the LBNF is a four-storey-high neutrino detector – dubbed the Deep Underground Neutrino Experiment (DUNE) – that will be built almost 1500 m underground in South Dakota. The detector is made up of four tanks that are each filled with 17,000 tonnes of liquid argon.

Underground journey

DUNE will measure the neutrinos that are generated by Fermilab, which lies around 1300 km away just outside Chicago. Fermilab will accelerate protons before smashing them into a piece of graphite. The particles that emerge from these collisions will go into a 200 m-long tunnel and decay into neutrinos. The neutrinos will first arrive at a “near detector” at Fermilab, where the beam will be characterized before heading on a 1300 km journey underground to DUNE. The neutrinos then interact with the liquid argon, which produces electrons that can be easily measured.

“The start of construction on this world-leading science experiment is cause for celebration, not just because of its positive impacts on the economy and on America’s strong relationships with our international partners, but also because of the fantastic discoveries that await us beyond the next horizon,” says US energy secretary Rick Perry. “I’m proud to support the efforts by Fermilab, Sanford Underground Research Facility and CERN, and we’re pleased to see it moving forward.”

Perovskites promise cheaper X-ray detectors

Recent studies have suggested that lead halide perovskites may end the search for the ideal X-ray photoconductor. Common solution-process protocols for fabricating thin films of these materials, however, are difficult to scale to the large areas required for X-ray detectors. In work recently published in Nature Photonics, a team of German researchers has presented an alternative, physical method of processing perovskites to solve this issue. The wafers produced using this sintering technique showed comparable performance to commercially available X-ray photodetectors.

The search for an ideal X-ray photoconductor has led researchers to hybrid organic-inorganic perovskites (HOIP), a class of materials that is already a major target for use in photovoltaics, light-emitting diodes and lasers. Current commercial detection systems based on materials like amorphous selenium and cadmium telluride are limited by low absorption coefficients and stability issues at high energies. HOIP materials, however, have the intrinsic ability to effectively absorb high-energy radiation because their composition includes heavy metal and halide ions. Perovskite X-ray detectors may therefore be a more effective alternative to existing detecting systems.

To date, much of the research has focused on solution-processing of perovskite thin films. While this is an efficient method for producing samples in the sub-micron regime, producing thicker layers, especially over large areas, is extremely difficult. This problem has so far hindered the development of perovskites for medical applications like X-ray detectors.

To get around this problem, first author Shreethu Shrestha and colleagues at Friedrich-Alexander-University Erlangen-Nürnberg in Germany, in collaboration with researchers at Siemens and the Bavarian Center for Applied Energy Research (ZAE Bayern), produced layers of perovskite using the physical method of sintering. Squeezing methyl ammonium triiodide perovskite (MAPbI3) powder in a hydraulic press for just five minutes, the researchers formed compact layers, or wafers, that were more than a centimetre in diameter. Depending on the amount of powder used, the resulting wafers ranged in thickness from 200 μm to 1 mm.

According to team member Gebhard Matt, also at Friedrich-Alexander-University Erlangen-Nürnberg, this was remarkable because such a sintering process is not possible for covalent semiconductors like silicon, which lack the plasticity of perovskites. As well as producing large-area detectors, sintering also allows the perovskites to be fabricated at room temperature, which makes the procedure simpler and cheaper than solution-processing.

Scanning electron microscopy (SEM), x-ray diffraction and photoluminescence confirmed that the crystallinity of the material was preserved after the sintering process. The grain boundaries of the microcrystals remain well defined following sintering, but, says Matt, “the surface of the wafers is as smooth as the surface of the cylinder in the hydraulic press”.

The group tested the X-ray performance of their wafers against a commercial cadmium telluride (CdTe) system, Timepix, which is the current state-of-the-art system for X-ray and gamma-ray detection. The group found that their MAPbI3-based detector had sensitivity and conversion values comparable to the Timepix system. CdTe is expensive, and only a few companies worldwide can produce the crystals, so even though the perovskites did not perform better than Timepix, their simpler preparation process makes them an attractive alternative.

Still, the researchers report that much work must be done prior to implementation of perovskite-based X-ray detectors. One major issue they encountered in their device was the presence of a high and unstable dark current. To fix this, the researchers now plan to explore carrier-selective electrodes to improve the performance still further.

More details can be found in Nature Photonics DOI: 10.1038/nphoton.2017.94.

How to detect gravitational waves using superfluid helium

Gravitational waves from nearby pulsars could be detected using just a few kilograms of superfluid helium-4, according to physicists in the US. Their detector, which is yet to be built, would measure sound waves in the superfluid caused by gravitational waves in the 0.1–1.5 kHz range.

Gravitational waves are ripples in space–time that are created when massive objects are accelerated under certain conditions. The first gravitational-wave detection was made in 2015, when the LIGO observatory spotted a signal from a coalescing binary black hole. Two more gravitational waves have since been detected by LIGO, both associated with binary black holes.

LIGO is a wideband detector that can detect signals in the 10 Hz–5 kHz range. It is particularly good at detecting transient signals (that change in frequency) associated with coalescing black holes.

Low-noise measurement

Swati Singh of Williams College, Laura DeLorenzo and Keith Schwab of Caltech and Igor Pikovski of Harvard University want to build a detector that can focus on a relatively narrow frequency band to detect gravitational waves from pulsars. A pulsar is a rapidly rotating neutron star that is expected to continually broadcast gravitational waves at a specific frequency in the 1 Hz–1 kHz range – with the frequency depending on the physical characteristics of the pulsar. By making a narrow-band measurement over a long period of time, a very low noise signal from a pulsar could in principle be detected.

Singh and colleagues’ detector comprises several kilograms of superfluid helium held in a cylindrical container that is coupled to microwaves in a superconductor resonator. Confinement in the container means that the superfluid will resonate with sound waves at certain frequencies – just like a musical instrument.

This acoustic resonance also means that the superfluid should act like an antenna that is tuned to detect gravitational waves at specific frequencies. When such a gravitational wave travels through the detector it would create a strain field that would create sound waves in the helium. The microwave resonator would then convert these waves into a measureable signal.

Adjustable frequency

Although others have tried to make such antennas using metal bars, the team says superfluid helium offers several benefits – including the fact that the frequency of the detector can be changed by adjusting the pressure of the helium.

Writing in New Journal of Physics, the team reckons that, using state-of-the-art microwave transducer technology, the detector could measure signals from certain types of pulsars after running several months.

Can four neutrons form a stable nucleus?

Is it possible for four neutrons to bind together to create an uncharged nucleus called a “tetraneutron”? The answer is a qualified “yes”, according to physicists in the US and France.

The idea of a tetraneutron goes back several decades, but it was not until in 2002 that the first tentative experimental evidence was found – by an international team of physicists working at the GANIL nuclear physics lab in France.

Near discovery

Then, in 2016, physicists working at the RIKEN nuclear-physics lab in Japan found evidence for tetraneutron in a different experiment that involved firing neutron-rich helium-8 nuclei at a helium-4 target. While they did not see direct evidence for a tetraneutron, careful measurements of the two helium-four particles produced in the collision suggest that the other four neutrons involved in the collision emerge in a bound state. The statistical significance of the measurement was 4.9σ – just shy of the 5σ needed for a discovery.

Despite this growing evidence, physicists do not have a clear theoretical understanding of how a tetraneutron could exist. Now, Kevin Fossez, Jimmy Rotureau and Nicolas Michel of the National Superconducting Cyclotron Laboratory at Michigan State University and Marek Płoszajczak of GANIL have done new calculations that are able to reproduce the energy of the tetraneutron observed at RIKEN.

Short lifetime

However, when the team used its method to calculate the energy width associated with the tetraneutron, the researchers found it to be significantly larger than that measured at RIKEN. A larger energy width corresponds to a short lifetime for the tetraneutron, and this has led the team to suggest that the four-neutron system may not stick around long enough to be considered to be a nucleus.

The research is described in Physical Review Letters.

Chiral metamaterial enables scatter-free propagation

A team of scientists from the UK and China has for the first time observed Fermi arcs – a distinct signature of the presence of topological properties – in a microwave metamaterial. Recent experiments have revealed Fermi arcs in quantum matter, but this is the first time they have been seen in a classical 3D system. The finding paves the way towards the study of a new class of topological optical materials, which could have important applications in communications because of their promise to send signals around corners or over defects without any loss of signal strength from scattering.

Fermi arcs are known to provide the connection between two topologically different surfaces in a quantum material called a Weyl semimetal. The electronic band structure in this material features so-called Weyl points, the 3D version of the Dirac points observed in graphene and other two-dimensional materials, where the dispersion is linear and the electronic bands cross each other. These Weyl points have a definite chirality, which can be understood as topological “charges”.

The researchers, led by Shuang Zhang from the University of Birmingham, therefore exploited chirality in the design of their topological metamaterial, along with hyperbolicity, to engineer the required dispersion. The material comprises a stacking of multiple tri-layers. The bottom layer possesses hyperbolic dispersion, which results from 200 μm-wide metallic wires running across its top surface, with metallic crosses superimposed on the wires to increase the capacitance and suppress non-local effects. The middle layer is a thin dielectric spacer that prevents electrical contact between top and bottom layers, while the top layer introduces chirality through the presence of metallic helices, each having 2.5 turns.

Backscattering-free surface wave propagating across a 3D step made of layers of chiral hyperbolic metamaterial (not to scale).

The researchers exploited a near-field scanning technique using microwave antannas to observe the Fermi arcs on both the top and side surfaces of their chiral hyperbolic metamaterial. The near-field distribution, once Fourier transformed into the frequency domain, clearly reveals the presence of Fermi arcs on the surface between the bulk states.

To further investigate the topological nature of the system, the group stacked several layers of the chiral hyperbolic metamaterial together to form a step. In this arrangement the topological protection of the surface state forces the surface wave excited at the top layer to bend around the step and to propagate forwards without any reflections from the edges. The absence of scattering as the surface wave propagates across the step confirms the topological nature of the chiral hyperbolic metamaterial.

One key feature of topologically protected states is that certain bands in the dispersion relation cannot interact, which means that a wave travelling in one band is not allowed to jump into another band. In this experiment, the researchers explain, the surface wave travels over the corner without any scattering because there is a topological charge difference between the Weyl points connected by the Fermi arc.

Next the researchers intend to investigate other systems that support topologically protected waves and find ways to more accurately steer waves on surfaces. Using simpler geometries, the group will be able to miniaturize these materials so that they can work at THz, infrared and optical frequencies.

The research has been published in Nature Communications.

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