Category Archives: medicine

Synthesizing nerve tissues with 3D printers and cellulose nanocrystals (CNC)

There are lots of stories about bioprinting and tissue engineering here and I think it’s time (again) for one which one has some good, detailed descriptions and, bonus, it features cellulose nanocrystals (CNC) and graphene. From a May 13, 2015 news item on Azonano,

The printer looks like a toaster oven with the front and sides removed. Its metal frame is built up around a stainless steel circle lit by an ultraviolet light. Stainless steel hydraulics and thin black tubes line the back edge, which lead to an inner, topside box made of red plastic.

In front, the metal is etched with the red Bio Bot logo. All together, the gray metal frame is small enough to fit on top of an old-fashioned school desk, but nothing about this 3D printer is old school. In fact, the tissue-printing machine is more like a sci-fi future in the flesh—and it has very real medical applications.

Researchers at Michigan Technological University hope to use this newly acquired 3D bioprinter to make synthesized nerve tissue. The key is developing the right “bioink” or printable tissue. The nanotechnology-inspired material could help regenerate damaged nerves for patients with spinal cord injuries, says Tolou Shokuhfar, an assistant professor of mechanical engineering and biomedical engineering at Michigan Tech.

Shokuhfar directs the In-Situ Nanomedicine and Nanoelectronics Laboratory at Michigan Tech, and she is an adjunct assistant professor in the Bioengineering Department and the College of Dentistry at the University of Illinois at Chicago.

In the bioprinting research, Shokuhfar collaborates with Reza Shahbazian-Yassar, the Richard and Elizabeth Henes Associate Professor in the Department of Mechanical Engineering-Engineering Mechanics at Michigan Tech. Shahbazian-Yassar’s highly interdisciplinary background on cellulose nanocrystals as biomaterials, funded by the National Science Foundation’s (NSF) Biomaterials Program, helped inspire the lab’s new 3D printing research. “Cellulose nanocrystals with extremely good mechanical properties are highly desirable for bioprinting of scaffolds that can be used for live tissues,” says Shahbazian-Yassar. [emphases mine]

A May 11, 2015 Michigan Technological University (MTU) news release by Allison Mills, which originated the news item, explains the ‘why’ of the research,

“We wanted to target a big issue,” Shokuhfar says, explaining that nerve regeneration is a particularly difficult biomedical engineering conundrum. “We are born with all the nerve cells we’ll ever have, and damaged nerves don’t heal very well.”

Other facilities are trying to address this issue as well. Many feature large, room-sized machines that have built-in cell culture hoods, incubators and refrigeration. The precision of this equipment allows them to print full organs. But innovation is more nimble at smaller scales.

“We can pursue nerve regeneration research with a simpler printer set-up,” says Shayan Shafiee, a PhD student working with Shokuhfar. He gestures to the small gray box across the lab bench.

He opens the red box under the top side of the printer’s box. Inside the plastic casing, a large syringe holds a red jelly-like fluid. Shafiee replenishes the needle-tipped printer, pulls up his laptop and, with a hydraulic whoosh, he starts to print a tissue scaffold.

The news release expands on the theme,

At his lab bench in the nanotechnology lab at Michigan Tech, Shafiee holds up a petri dish. Inside is what looks like a red gummy candy, about the size of a half-dollar.

Here’s a video from MTU illustrating the printing process,

Back to the news release, which notes graphene could be instrumental in this research,

“This is based on fractal geometry,” Shafiee explains, pointing out the small crenulations and holes pockmarking the jelly. “These are similar to our vertebrae—the idea is to let a nerve pass through the holes.”

Making the tissue compatible with nerve cells begins long before the printer starts up. Shafiee says the first step is to synthesize a biocompatible polymer that is syrupy—but not too thick—that can be printed. That means Shafiee and Shokuhfar have to create their own materials to print with; there is no Amazon.com or even a specialty shop for bioprinting nerves.

Nerves don’t just need a biocompatible tissue to act as a carrier for the cells. Nerve function is all about electric pulses. This is where Shokuhfar’s nanotechnology research comes in: Last year, she was awarded a CAREER grant from NSF for her work using graphene in biomaterials research. [emphasis mine] “Graphene is a wonder material,” she says. “And it has very good electrical conductivity properties.”

The team is extending the application of this material for nerve cell printing. “Our work always comes back to the question, is it printable or not?” Shafiee says, adding that a successful material—a biocompatible, graphene-bound polymer—may just melt, mush or flat out fail under the pressure of printing. After all, imagine building up a substance more delicate than a soufflé using only the point of a needle. And in the nanotechnology world, a needlepoint is big, even clumsy.

Shafiee and Shokuhfar see these issues as mechanical obstacles that can be overcome.

“It’s like other 3D printers, you need a design to work from,” Shafiee says, adding that he will tweak and hone the methodology for printing nerve cells throughout his dissertation work. He is also hopeful that the material will have use beyond nerve regeneration.

This looks like a news release designed to publicize work funded at MTU by the US National Science Foundation (NSF) which is why there is no mention of published work.

One final comment regarding cellulose nanocrystals (CNC). They have also been called nanocrystalline cellulose (NCC), which you will still see but it seems CNC is emerging as the generic term. NCC has been trademarked by CelluForce, a Canadian company researching and producing CNC (or if you prefer, NCC) from forest products.

Measuring a singular spin of a biological molecule

I gather there are some Swiss scientists excited about obtaining experimental proof for room temperature detection of a  biological molecule’s spin. From a May 11, 2015 news item on Nanowerk (Note: A link has been removed),

Physicists of the University of Basel and the Swiss Nanoscience Institute were able to show for the first time that the nuclear spins of single molecules can be detected with the help of magnetic particles at room temperature.

In Nature Nanotechnology (“High-efficiency resonant amplification of weak magnetic fields for single spin magnetometry at room temperature”), the researchers describe a novel experimental setup with which the tiny magnetic fields of the nuclear spins of single biomolecules – undetectable so far – could be registered for the first time. The proposed concept would improve medical diagnostics as well as analyses of biological and chemical samples in a decisive step forward.

A May 11, 2015 University of Basel press release, which originated the news item, explains why the researchers are excited about a ‘room temperature’ approach to measuring a nuclear spin,

The measurement of nuclear spins is routine by now in medical diagnostics (MRI). However, the currently existing devices need billions of atoms for the analysis and thus are not useful for many small-scale applications. Over many decades, scientists worldwide have thus engaged in an intense search for alternative methods, which would improve the sensitivity of the measurement techniques.

With the help of various types of sensors (SQUID- and Hall-sensors) and with magnetic resonance force microscopes, it has become possible to detect spins of single electrons and achieve structural resolution at the nanoscale. However, the detection of single nuclear spins of complex biological samples – the holy grail in the field – has not been possible so far.

Diamond crystals with tiny defects

The researchers from Basel now investigate the application of sensors made out of diamonds that host tiny defects in their crystal structure. In the crystal lattice of the diamond a Carbon atom is replaced by a Nitrogen atom, with a vacant site next to it. These so-called Nitrogen-Vacancy (NV) centers generate spins, which are ideally suited for detection of magnetic fields. At room temperature, researchers have shown experimentally in many labs before that with such NV centers resolution of single molecules is possible. However, this requires atomistically close distances between sensor and sample, which is not possible for biological material.

A tiny ferromagnetic particle, placed between sample and NV center, can solve this problem. Indeed, if the nuclear spin of the sample is driven at a specific resonance frequency, the resonance of the ferromagnetic particle changes. With the help of an NV center that is in close proximity of the magnetic particle, the scientists can then detect this modified resonance.

Measuring technology breakthrough?

The theoretical analysis and experimental techniques of the researchers in the teams of Prof. Daniel Loss and Prof. Patrick Maletinsky have shown that the use of such ferromagnetic particles can lead to a ten-thousand-fold amplification of the magnetic field of nuclear spins. „I am confident that our concept will soon be implemented in real systems and will lead to a breakthrough in metrology“ [science of measurement], comments Daniel Loss the recent publication, where the first author Dr. Luka Trifunovic, postdoc in the Loss team, made essential contributions and which was performed in collaboration with colleagues from the JARA Institute for Quantum Information (Aachen, Deutschland) and the Harvard University (Cambridge, USA).

Here’s a link to and a citation for the paper,

High-efficiency resonant amplification of weak magnetic fields for single spin magnetometry at room temperature by  Luka Trifunovic, Fabio L. Pedrocchi, Silas Hoffman, Patrick Maletinsky, Amir Yacoby, & Daniel Loss. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.74 Published online 11 May 2015

This paper is behind a paywall.

Are you sure my artificial muscles don’t smell like onions?

A May 5, 2015 news item on ScienceDaily highlights some research on artificial muscles from the National Taiwan University,

Just one well-placed slice into a particularly pungent onion can send even the most seasoned chef running for a box of tissues. Now, this humble root vegetable is proving its strength outside the culinary world as well — in an artificial muscle created from onion cells. Unlike previous artificial muscles, this one, created by a group of researchers from National Taiwan University, can either expand or contract to bend in different directions depending on the driving voltage applied.

A May 5, 2015 American Institute of Physics (AIP) news release by Laurel Hamers,  which originated the news item, describes the research goals,

“The initial goal was to develop an engineered microstructure in artificial muscles for increasing the actuation deformation [the amount the muscle can bend or stretch when triggered],” said lead researcher Wen-Pin Shih. “One day, we found that the onion’s cell structure and its dimensions were similar to what we had been making.” Shih lead the study along with graduate student Chien-Chun Chen and their colleagues.

The onion epidermis — the fragile skin found just beneath the onion’s surface — is a thin, translucent layer of blocky cells arranged in a tightly-packed lattice. Shih and his colleagues thought that onion epidermal cells might be a viable candidate for the tricky task of creating a more versatile muscle that could expand or contract while bending. To date, Shih said, artificial muscles can either bend or contract, but not at the same time.

The researchers treated the cells with acid to remove the hemicellulose, a protein that makes the cell walls rigid. Then, they coated both sides of the onion layer with gold. When current flowed through the gold electrodes, the onion cells bent and stretched much like a muscle.

“We intentionally made the top and bottom electrodes a different thickness so that the cell stiffness becomes asymmetric from top to bottom,” said Shih. The asymmetry gave the researchers control over the muscle’s response: a low voltage made them expand and flex downwards, towards the thicker bottom layer. A high voltage, on the other hand, caused the cells to contract and flex upwards, towards the thinner top layer.

“We found that the single-layer lattice structure can generate unique actuation modes that engineered artificial muscle has never achieved before,” said Shih.

To demonstrate their device’s utility, the researchers combined two onion muscles into a pair of tweezers, which they used to pick up a cotton ball. In the future, they hope to increase the lifting power of their artificial muscles. “Our next step is to reduce the driving voltage and the actuating force,” said Shih.

Here’s a link to and a citation for the paper,

Onion artificial muscles by Chien-Chun Chen, Wen-Pin Shih, Pei-Zen Chang, Hsi-Mei Lai, Shing-Yun Chang, Pin-Chun Huang and Huai-An Jeng. Appl. Phys. Lett. 106, 183702 (2015); http://dx.doi.org/10.1063/1.4917498

This appears to be open access.

Customizing DNA nanotubes quickly and cheaply

Building on some work published earlier this year, scientists from McGill University (Montréal, Québec) created a new technique for building DNA nanotubes block by block (my March 2, 2015 posting) and, now, the newest research from the McGill team features a way of making long DNA strands with that technique, as mentioned in a May 7, 2015 news item on Azonano,

Imagine taking strands of DNA – the material in our cells that determines how we look and function – and using it to build tiny structures that can deliver drugs to targets within the body or take electronic miniaturization to a whole new level.

While it may still sound like science fiction to most of us, researchers have been piecing together and experimenting with DNA structures for decades. And, in recent years, work by scientists such as McGill University chemistry professor Hanadi Sleiman has moved the use of man-made DNA structures closer to a variety of real-world applications.

But as these applications continue to develop, they require increasingly large and complex strands of DNA. That has posed a problem, because the automated systems used for making synthetic DNA can’t produce strands containing more than about 100 bases (the chemicals that link up to form the strands). It can take hundreds of these short strands to assemble nanotubes for applications such as smart drug-delivery systems.

Here’s a video featuring one of the researchers taking about this latest work from McGill University,

A May 6, 2015 McGill University news release, which originated the news item, describes the long DNA nanotubes in more detail,

In new research published May 5 in Nature Communications, however, Sleiman’’s team at McGill reports that it has devised a technique to create much longer strands of DNA, including custom-designed sequence patterns. What’s more, this approach also produces large amounts of these longer strands in just a few hours, making the process potentially more economical and commercially viable than existing techniques.

The new method involves piecing together small strands one after the other, so that they attach into a longer DNA strand with the help of an enzyme known as ligase.  A second enzyme, polymerase, is then used to generate many copies of the long DNA strand, yielding larger volumes of the material. The polymerase process has the added advantage of correcting any errors that may have been introduced into the sequence, amplifying only the correctly sequenced, full-length product.

Designer DNA materials

The team used these strands as a scaffold to make DNA nanotubes, demonstrating that the technique allows the length and functions of the tubes to be precisely programmed. “In the end, what we get is a long, synthetic DNA strand with exactly the sequence of bases that we want, and with exactly as many repeat units as we want,” explains Sleiman, who co-authored the study with Graham Hamblin, who recently completed his doctorate, and PhD student Janane Rahbani.

“This work opens the door toward a new design strategy in DNA nanotechnology,” Sleiman says. “This could provide access to designer DNA materials that are economical and can compete with cheaper, but less versatile technologies. In the future, uses could range from customized gene and protein synthesis, to applications in nanoelectronics, nano-optics, and medicine, including diagnosis and therapy.”

Here’s a link to and a citation for the paper,

Sequential growth of long DNA strands with user-defined patterns for nanostructures and scaffolds by Graham D. Hamblin, Janane F. Rahbani, & Hanadi F. Sleiman. Nature Communications 6, Article number: 7065 doi:10.1038/ncomms8065 Published 05 May 2015

This article is behind a paywall.

Gold and your neurons

Should you need any electrode implants for your neurons at some point in the future, it’s possible they could be coated with gold. Researchers at the Lawrence Livermore National Laboratory (LLNL) and at the University of California at Davis (UC Davis) have discovered that electrodes covered in nanoporous gold could prevent scarring (from a May 5, 2015 news item on Azonano),

A team of researchers from Lawrence Livermore and UC Davis have found that covering an implantable neural electrode with nanoporous gold could eliminate the risk of scar tissue forming over the electrode’s surface.

The team demonstrated that the nanostructure of nanoporous gold achieves close physical coupling of neurons by maintaining a high neuron-to-astrocyte surface coverage ratio. Close physical coupling between neurons and the electrode plays a crucial role in recording fidelity of neural electrical activity.

An April 30, 2015 LLNL news release, which originated the news item, details the scarring issue and offers more information about the proposed solution,

Neural interfaces (e.g., implantable electrodes or multiple-electrode arrays) have emerged as transformative tools to monitor and modify neural electrophysiology, both for fundamental studies of the nervous system, and to diagnose and treat neurological disorders. These interfaces require low electrical impedance to reduce background noise and close electrode-neuron coupling for enhanced recording fidelity.

Designing neural interfaces that maintain close physical coupling of neurons to an electrode surface remains a major challenge for both implantable and in vitro neural recording electrode arrays. An important obstacle in maintaining robust neuron-electrode coupling is the encapsulation of the electrode by scar tissue.

Typically, low-impedance nanostructured electrode coatings rely on chemical cues from pharmaceuticals or surface-immobilized peptides to suppress glial scar tissue formation over the electrode surface, which is an obstacle to reliable neuron−electrode coupling.

However, the team found that nanoporous gold, produced by an alloy corrosion process, is a promising candidate to reduce scar tissue formation on the electrode surface solely through topography by taking advantage of its tunable length scale.

“Our results show that nanoporous gold topography, not surface chemistry, reduces astrocyte surface coverage,” said Monika Biener, one of the LLNL authors of the paper.

Nanoporous gold has attracted significant interest for its use in electrochemical sensors, catalytic platforms, fundamental structure−property studies at the nanoscale and tunable drug release. It also features high effective surface area, tunable pore size, well-defined conjugate chemistry, high electrical conductivity and compatibility with traditional fabrication techniques.

“We found that nanoporous gold reduces scar coverage but also maintains high neuronal coverage in an in vitro neuron-glia co-culture model,” said Juergen Biener, the other LLNL author of the paper. “More broadly, the study demonstrates a novel surface for supporting neuronal cultures without the use of culture medium supplements to reduce scar overgrowth.”

Here’s a link to and a citation for the paper,

Nanoporous Gold as a Neural Interface Coating: Effects of Topography, Surface Chemistry, and Feature Size by Christopher A. R. Chapman, Hao Chen, Marianna Stamou, Juergen Biener, Monika M. Biener, Pamela J. Lein, and Erkin Seker. ACS Appl. Mater. Interfaces, 2015, 7 (13), pp 7093–7100 DOI: 10.1021/acsami.5b00410 Publication Date (Web): February 23, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

The researchers have provided this image to illustrate their work,

The image depicts a neuronal network growing on a novel nanotextured gold electrode coating. The topographical cues presented by the coating preferentially favor spreading of neurons as opposed to scar tissue. This feature has the potential to enhance the performance of neural interfaces. Image by Ryan Chen/LLNL.

The image depicts a neuronal network growing on a novel nanotextured gold electrode coating. The topographical cues presented by the coating preferentially favor spreading of neurons as opposed to scar tissue. This feature has the potential to enhance the performance of neural interfaces. Image by Ryan Chen/LLNL.

Virtual Reality (VR) becomes educational (at Case Western Reserve University and Miami Children’s Hospital)

I have two virtual reality news bits the most recent concerning Case Western Reserve University (CWRU; located in Cleveland, Ohio) and Microsoft’s HoloLens in an April 29, 2015 CWRU press release (also on EurekAlert), Note: Some of this academic press release reads like marketing collateral,

Case Western Reserve University Radiology Professor Mark Griswold knew his world had changed the moment he first used a prototype of Microsoft’s HoloLens headset. Two months later, one of the university’s medical students illustrated exactly why.

“There’s the aortic valve,” Satyam Ghodasara exclaimed as he used Microsoft’s device to examine a holographic heart. “Now I understand.”

Today, Griswold told tens of thousands of people how HoloLens can transform learning across countless subjects, including those as complex as the human body. Speaking to an in-person and online audience at Microsoft’s annual Build conference, he highlighted disciplines as disparate as art history and engineering–but started with a holographic heart. In traditional anatomy, after all, students like Ghodasara cut into cadavers to understand the body’s intricacies.

With HoloLens, Griswold explained, “you see it truly in 3D. You can take parts in and out. You can turn it around. You can see the blood pumping–the entire system.”

In other words, technology not only can match existing educational methods–it can actually improve upon them. Which, in many ways, is why Cleveland Clinic CEO Toby Cosgrove contacted then-Microsoft executive Craig Mundie in 2013, after the hospital and university first agreed to partner on a new education building.

“We launched this collaboration to prepare students for a health care future that is still being imagined,” Cleveland Clinic CEO Delos “Toby” Cosgrove said of what has become a 485,000-square-foot Health Education Campus project. “By combining a state-of-the-art structure, pioneering technology, and cutting-edge teaching techniques, we will provide them the innovative education required to lead in this new era.”

As Cosgrove, Case Western Reserve President Barbara R. Snyder and other academic leaders engaged more extensively with Microsoft, the more potential everyone saw.

“For more than a century, our medical school has been renowned for inventing and reinventing approaches to teaching and learning that take root nationwide,” President Snyder said. “When we match that expertise with the interdisciplinary knowledge of our faculty, we create a rich environment to explore the educational potential of Microsoft’s extraordinary technology.”

After a small group including Griswold, engineering professor Marc Buchner and Cleveland Clinic education technology leader Neil Mehta first experienced HoloLens in December, the faculty returned to Cleveland to create a core team dedicated to exploring the technology’s academic potential. In February, 10 members of the team–including Ghodasara–returned to Microsoft for a HoloLens programming deep dive.

Ghodasara already had taken the traditional anatomy class at Case Western Reserve, but it wasn’t until he used the HoloLens headset that he first visualized the aortic valve in its entirety–unobstructed by other elements of the cardiac system and undamaged by earlier dissection efforts. Members of the Microsoft team were in the room when Ghodasara had his “aha” moment; a few weeks later, the heart demonstration became part of the Build conference agenda.

Case Western Reserve is the only university represented during the three-day event, a distinction Griswold attributes in part to the core team’s breadth of expertise and collegial approach.

“Without all of those people coming together,” Griswold said, “this would not have happened.”

When Griswold took the stage as part of Microsoft’s opening keynote at the Build conference, Ghodasara, Buchner and Chief Information Officer Sue Workman also were in the audience. Back in Cleveland, three of Professor Buchner’s undergraduates–John Billingsley, Henry Eastman and Tim Sesler–demonstrated some of the potential of the HoloLens technology live in the Tinkham Veale University Center.

Buchner, whose specialties include simulation and game design, believes Microsoft’s innovation “has the capability to transform engineering education.”

Because the technology is relatively easy to use, students will be able to build, operate and analyze all manner of devices and systems. “[It will] encourage experimentation,” Buchner said, “leading to deeper understanding and improved product design.”

In truth, HoloLens ultimately could have applications for dozens of Case Western Reserve’s academic programs. NASA’s Jet Propulsion Laboratory already has worked with Microsoft to develop software that will allow Earth-based scientists to work on Mars with a specially designed rover vehicle. A similar collaboration could enable students here to take part in archeological digs around the world. Or astronomy students could stand in the midst of colliding galaxies, securing front-row view of the unfolding chaos. Art history professors could present masterpieces in their original settings–a centuries-old castle, or even the Sistine Chapel.

“The whole campus has the potential to use this,” Griswold said. “Our ability to use this for education is almost limitless.”

For now, however, the top priority is creating a full digital anatomy curriculum, a process launched with the advent of the Health Education Campus, and now experiencing even greater momentum. Among the key collaborators are a team of medical students and anatomy and radiology faculty who are already investigating the use of these kinds of technology. This team, led by Amy Wilson­Delfosse, the medical school’s associate dean for curriculum, and Suzanne Wish-Baratz, an assistant professor who is one of the primary leaders of anatomy education, fully expects to have a digital curriculum ready for the new Health Education Campus.

Also essential, Griswold said, has been the advice and assistance of Microsoft’s HoloLens team and executives.

“It’s been a joy to work with them. They have been so friendly, so collaborative, so willing to work with us on this,” Griswold said. “We’re going to do incredible things together.”

Ohio is not the only state where virtual reality is being incorporated into medical education.

Florida

From an April 30, 2015 Next Galaxy Corp. news release,

Incorporating eye gaze control, gestures, and voice commands while “walking around” inside an emergency medical experience, Next Galaxy’s Virtual Reality Model educates participants far beyond today’s methodology of passively watching video and taking written tests.

Next Galaxy Corp (OTC: NXGA) recently announced the signing of an agreement with Miami Children’s Hospital to use the Company’s VR Model to develop immersive Virtual Reality medical instructional content for patient and medical professional education. Per the multi-year agreement, Next Galaxy and Miami Children’s Hospital are jointly developing VR Instructionals on cardiopulmonary resuscitation (CPR) and other lifesaving procedures, which will be released as an application for smartphones.

Assessments are incorporated directly into the medical VR models, creating situations where participants are required to make the appropriate decisions about proper techniques. The Virtual CPR instructional will measure metrics and provide real-time feedback ensuring participants accurately perform CPR techniques. Further, the instructional will explain any mistake and prompt users to try again when errors are made. Supportive messages are delivered upon success.

The medical VR models will be viewable through smartphones and desktops as 3D, and via VR devices such as Google Cardboard, VRONE and Oculus Rift.

About Next Galaxy Corporation

Next Galaxy Corporation is a leading developer of innovative content solutions and fully Immersive Consumer Virtual Reality technology. The Company’s flagship consumer product in development is CEEK, a next-generation fully immersive entertainment and educational social virtual reality platform featuring a combination of live action and 3D experiences. Next Galaxy’s CEEK simulates the communal experience of attending events, such as concerts, sporting events, movies or conferences through Virtual Reality. Next Galaxy is developing entertainment and educational experiences for VR Cinema, VR Concerts, VR Sports, VR Business, VR Tourism and more. In short, Next Galaxy is building the meeting places of the future. For further information, visit www.nextgalaxycorp.com

This seems to be the second time this information has been distributed (March 11, 2015 news release on PRNewswire), a widely adopted practice. Consequently and thankfully, there’s a March 11, 2015 article by Celia Ampel for the South Florida Business Journal which provides more details about the technology and explaining how a smartphone fits into virtual reality,

The best way to learn CPR is an immersive experience, Miami Children’s Hospital leaders believe — not a video.

“If I’m watching a video, I can pause and count, but there’s no way to tell if I counted to six or seven,” Next Galaxy President Mary Spio said. “Because [the virtual reality application] is voice-activated, they’re going to be able to count out loud and self-assess whether they’re doing it correctly.”

Next Galaxy (Pink Sheets: NXGA)’s virtual reality technology uses a smartphone app. Users can put their smartphone into a virtual reality headset for an immersive experience, or see 3D content through the phone.

The application will be available to the public in the next few months, Spio said.

This deal and another with Miami-Dade Country Public Schools are transforming Next Galaxy Corp according to Ampel’s article,

The five-person company will be hiring about 20 full-time employees in the next six months, focusing on developers with 3D modeling and gaming experience, she said.

Quadrupling the size of your company in six months can be quite a challenge. I wish them good luck with their expansion and their virtual reality course materials.

As to what all this mixed-reality/virtual reality might look like, there’s this image from Case Western Reserve University,

Courtesy: Case Western Reserve University

Courtesy: Case Western Reserve University

Wound healing is nature’s way of zipping up your skin

Scientists have been able to observe the healing process at the molecular scale—in fruit flies. From an April 21, 2015 news item on ScienceDaily,

Scientists from the Goethe University (GU) Frankfurt, the European Molecular Biology Laboratory (EMBL) Heidelberg and the University of Zurich explain skin fusion at a molecular level and pinpoint the specific molecules that do the job in their latest publication in the journal Nature Cell Biology.

An April 21, 2015 Goethe University Frankfurt press release on EurekAlert, which originated the news item, describes similarities between humans and fruit flies allowing scientists to infer the wound healing process for human skin,

In order to prevent death by bleeding or infection, every wound (skin opening) must close at some point. The events leading to skin closure had been unclear for many years. Mikhail Eltsov (GU) and colleagues used fruit fly embryos as a model system to understand this process. Similarly to humans, fruit fly embryos at some point in their development have a large opening in the skin on their back that must fuse. This process is called zipping, because two sides of the skin are fastened in a way that resembles a zipper that joins two sides of a jacket.

The scientists have used a top-of-the-range electron microscope to study exactly how this zipping of the skin works. “Our electron microscope allows us to distinguish the molecular components in the cell that act like small machines to fuse the skin. When we look at it from a distance, it appears as if skin cells simply fuse to each other, but if we zoom in, it becomes clear that membranes, molecular machines, and other cellular components are involved”, explains Eltsov.

“In order to visualize this orchestra of healing, a very high-resolution picture of the process is needed. For this purpose we have recorded an enormous amount of data that surpasses all previous studies of this kind”, says Mikhail Eltsov.

As a first step, as the scientists discovered, cells find their opposing partner by “sniffing” each other out. As a next step, they develop adherens junctions which act like a molecular Velcro. This way they become strongly attached to their opposing partner cell. The biggest revelation of this study was that small tubes in the cell, called microtubules, attach to this molecular Velcro and then deploy a self-catastrophe, which results in the skin being pulled towards the opening, as if one pulls a blanket over.

Damian Brunner who led the team at the University of Zurich has performed many genetic manipulations to identify the correct components. The scientists were astonished to find that microtubules involved in cell-division are the primary scaffold used for zipping, indicating a mechanism conserved during evolution.

“What was also amazing was the tremendous plasticity of the membranes in this process which managed to close the skin opening in a very short space of time. When five to ten cells have found their respective neighbors, the skin already appears normal”, says Achilleas Frangakis from the Goethe University Frankfurt, who led the study.

The scientists hope that their results will open new avenues into the understanding of epithelial plasticity and wound healing. They are also investigating the detailed structural organization of the adherens junctions, work for which they were awarded a starting grant from European Research Council (ERC).

Here’s a link to and a citation for the paper,

Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography by Mikhail Eltsov, Nadia Dubé, Zhou Yu, Laurynas Pasakarnis, Uta Haselmann-Weiss, Damian Brunner, & Achilleas S. Frangakis. Nature Cell Biology (2015) doi:10.1038/ncb3159 Published online 20 April 2015

This paper is behind a paywall but there is a free preview available via ReadCube Access.

The researchers have provided an image illustrating ‘wound zipping’.

Caption: This is a perspective view of the zipping area with 17 skin cells. Credit: GU

Caption: This is a perspective view of the zipping area with 17 skin cells.
Credit: GU

Maple syrup as an antibiotic helper?

This maple syrup research is from McGill University in Montréal, Québec (from an April 16, 2015 McGill University news release; also on EurekAlert),

A concentrated extract of maple syrup makes disease-causing bacteria more susceptible to antibiotics, according to laboratory experiments by researchers at McGill University.

The findings, which will be published in the journal Applied and Environmental Microbiology, suggest that combining maple syrup extract with common antibiotics could increase the microbes’ susceptibility, leading to lower antibiotic usage. Overuse of antibiotics fuels the emergence of drug-resistant bacteria, which has become a major public-health concern worldwide.

Prof. Nathalie Tufenkji’s research team in McGill’s Department of Chemical Engineering prepared a concentrated extract of maple syrup that consists mainly of phenolic compounds. Maple syrup, made by concentrating the sap from North American maple trees, is a rich source of phenolic compounds.

The researchers tested the extract’s effect in the laboratory on infection-causing strains of certain bacteria, including E. coli and Proteus mirabilis (a common cause of urinary tract infection). By itself, the extract was mildly effective in combating bacteria. But the maple syrup extract was particularly effective when applied in combination with antibiotics. The extract also acted synergistically with antibiotics in destroying resistant communities of bacteria known as biofilms, which are common in difficult-to-treat infections, such as catheter-associated urinary tract infections.

“We would have to do in vivo tests, and eventually clinical trials, before we can say what the effect would be in humans,” Tufenkji says. “But the findings suggest a potentially simple and effective approach for reducing antibiotic usage. I could see maple syrup extract being incorporated eventually, for example, into the capsules of antibiotics.”

The scientists also found that the extract affects the gene expression of the bacteria, by repressing a number of genes linked with antibiotic resistance and virulence.

All maple syrup samples used in the study were purchased at local markets in Montreal, then frozen until the beginning of each experiment, which involved a series of steps to produce the phenolic-rich extract.

Tufenkji, who holds the Canada Research Chair in Biocolloids and Surfaces, has also studied the potential for cranberry derivatives to fight infection-causing bacteria. The new study is co-authored by postdoctoral fellows Vimal Maisuria and Zeinab Hosseinidoust.

Here’s a link to and a citation for the paper which at this time (April 24, 2014) is not yet published,,

Polyphenolic Extract from Maple Syrup Potentiates Antibiotic Susceptibility and Reduces Biofilm Formation of Pathogenic Bacteria by Vimal B. Maisuria, Zeinab Hosseinidoust, and Nathalie Tufenkji. doi: 10.1128/AEM.00239-15 AEM [Applied and Environmental Microbiology].00239-15

My guess is that this paper will be behind a paywall. Fear not! There is a very informative 3 mins. or so video,

I particularly appreciated the maple leaf-shaped glass container (still full) which is shown prominently when the researcher mentions purchasing the syrup from local markets.

Reversing Parkinson’s type symptoms in rats

Indian scientists have developed a technique for delivering drugs that could reverse Parkinson-like symptoms according to an April 22, 2015 news item on Nanowerk (Note: A link has been removed),

As baby boomers age, the number of people diagnosed with Parkinson’s disease is expected to increase. Patients who develop this disease usually start experiencing symptoms around age 60 or older. Currently, there’s no cure, but scientists are reporting a novel approach that reversed Parkinson’s-like symptoms in rats.

Their results, published in the journal ACS Nano (“Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats”), could one day lead to a new therapy for human patients.

An April 22, 2015 American Chemical Society press pac news release (also on EurekAlert), which originated the news item, describes the problem the researchers were solving (Note: Links have been removed),

Rajnish Kumar Chaturvedi, Kavita Seth, Kailash Chand Gupta and colleagues from the CSIR-Indian Institute of Toxicology Research note that among other issues, people with Parkinson’s lack dopamine in the brain. Dopamine is a chemical messenger that helps nerve cells communicate with each other and is involved in normal body movements. Reduced levels cause the shaking and mobility problems associated with Parkinson’s. Symptoms can be relieved in animal models of the disease by infusing the compound into their brains. But researchers haven’t yet figured out how to safely deliver dopamine directly to the human brain, which is protected by something called the blood-brain barrier that keeps out pathogens, as well as many medicines. Chaturvedi and Gupta’s team wanted to find a way to overcome this challenge.

The researchers packaged dopamine in biodegradable nanoparticles that have been used to deliver other therapeutic drugs to the brain. The resulting nanoparticles successfully crossed the blood-brain barrier in rats, released its dopamine payload over several days and reversed the rodents’ movement problems without causing side effects.

The authors acknowledge funding from the Indian Department of Science and Technology as Woman Scientist and Ramanna Fellow Grant, and the Council of Scientific and Industrial Research (India).

Here’s a link to and citation for the paper,

Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats by Richa Pahuja, Kavita Seth, Anshi Shukla, Rajendra Kumar Shukla, Priyanka Bhatnagar, Lalit Kumar Singh Chauhan, Prem Narain Saxena, Jharna Arun, Bhushan Pradosh Chaudhari, Devendra Kumar Patel, Sheelendra Pratap Singh, Rakesh Shukla, Vinay Kumar Khanna, Pradeep Kumar, Rajnish Kumar Chaturvedi, and Kailash Chand Gupta. ACS Nano, Article ASAP DOI: 10.1021/nn506408v Publication Date (Web): March 31, 2015
Copyright © 2015 American Chemical Society

This paper is open access.

Another recent example of breaching the blood-brain barrier, coincidentally, in rats, can be found in my Dec. 24, 2014 titled: Gelatin nanoparticles for drug delivery after a stroke. Scientists are also trying to figure out the the blood-brain barrier operates in the first place as per this April 22, 2015 University of Pennsylvania news release on EurekAlert titled, Penn Vet, Montreal and McGill researchers show how blood-brain barrier is maintained (University of Pennsylvania School of Veterinary Medicine, University of Montreal or Université de Montréal, and McGill University). You can find out more about CSIR-Indian Institute of Toxicology Research here.

Electronic organic micropump for direct drug delivery to the brain

I can understand the appeal but have some questions about this micropump in the brain concept. First, here’s more about the research from an April 16, 2015 news item on Nanowerk,

Many potentially efficient drugs have been created to treat neurological disorders, but they cannot be used in practice. Typically, for a condition such as epilepsy, it is essential to act at exactly the right time and place in the brain. For this reason, the team of researchers led by Christophe Bernard at Inserm Unit 1106, “Institute of Systems Neuroscience” (INS), with the help of scientists at the École des Mines de Saint-Étienne and Linköping University (Sweden) have developed an organic electronic micropump which, when combined with an anticonvulsant drug, enables localised inhibition of epileptic seizure in brain tissue in vitro.

An April 16, 2015 INSERM (Institut national de la santé et de la recherche médicale) press release on EurekAlert, which originated the news item, goes on to describe the problem the researchers are attempting to solve and their solution to it,

Drugs constitute the most widely used approach for treating brain disorders. However, many promising drugs failed during clinical testing for several reasons:

  • they are diluted in potentially toxic solutions,
  • they may themselves be toxic when they reach organs to which they were not initially directed,
  • the blood-brain barrier, which separates the brain from the blood circulation, prevents most drugs from reaching their targets in the brain,
  • drugs that succeed in penetrating the brain will act in a non-specific manner, i.e. on healthy regions of the brain, altering their functions.

Epilepsy is a typical example of a condition for which many drugs could not be commercialised because of their harmful effects, when they might have been effective for treating patients resistant to conventional treatments [1].

During an epileptic seizure, the nerve cells in a specific area of the brain are suddenly activated in an excessive manner. How can this phenomenon be controlled without affecting healthy brain regions? To answer this question, Christophe Bernard’s team, in collaboration with a team led by George Malliaras at the Georges Charpak-Provence Campus of the École des Mines of Saint-Étienne and Swedish scientists led by Magnus Berggren from Linköping University, have developed a biocompatible micropump that makes it possible to deliver therapeutic substances directly to the relevant areas of the brain.

The micropump (20 times thinner than a hair) is composed of a membrane known as “cation exchange,” i.e., it has negative ions attached to its surface. It thus attracts small positively charged molecules, whether these are ions or drugs. When an electrical current is applied to it, the flow of electrons generated projects the molecules of interest toward the target area.

To enable validation of this new technique, the researchers reproduced the hyperexcitability of epileptic neurons in mouse brains in vitro. They then injected GABA, a compound naturally produced in the brain and that inhibits neurons, into this hyperactive region using the micropump. The scientists then observed that the compound not only stopped this abnormal activity in the target region, but, most importantly, did not interfere with the functioning of the neighbouring regions.

This technology may thus resolve all the above-mentioned problems, by allowing very localised action, directly in the brain and without peripheral toxicity.

“By combining electrodes, such as those used to treat Parkinson’s disease, with this micropump, it may be possible to use this technology to treat patients with epilepsy who are resistant to conventional treatments, and those for whom the side-effects are too great,” explains Christophe Bernard, Inserm Research Director.

Based on these initial results, the researchers are now working to move on to an in vivo animal model and the possibility of combining this high-technology system with the microchip they previously developed in 2013. The device could be embedded and autonomous. The chip would be used to detect the imminent occurrence of a seizure, in order to activate the pump to inject the drug at just the right moment. It may therefore be possible to control brain activity where and when it is needed.

In addition to epilepsy, this state-of-the-art technology, combined with existing drugs, offers new opportunities for many brain diseases that remain difficult to treat at this time.

###

[1] Epilepsy in brief

This disease, which affects nearly 50 million people in the world, is the most common neurological disorder after migraine.

The neuronal dysfunctions associated with epilepsy lead to attacks with variable symptoms, from loss of consciousness to disorders of movement, sensation or mood.

Despite advances in medicine, 30% of those affected are resistant to all treatments.

Here’s a link to and a citation for the paper,

Controlling Epileptiform Activity with Organic Electronic Ion Pumps by Adam Williamson, Jonathan Rivnay, Loïg Kergoat, Amanda Jonsson, Sahika Inal, Ilke Uguz, Marc Ferro, Anton Ivanov, Theresia Arbring-Sjöström, Daniel T. Simon, Magnus Berggren, George G. Malliaras, and Christophe Bernardi. Advanced Materials First published: 11 April 2015Full publication history DOI: 10.1002/adma.201500482

This paper is behind a paywall.

Finally, my questions. How does the pump get refilled once the drugs are used up? Do you get a warning when the drug supply is almost nil? How does that warning work? Does implanting the pump require brain surgery or is there a less intrusive fashion of placing this pump exactly where you want it to be? Once it’s been implanted, how do you find a pump  20 times thinner than a human hair?

For some reason this micropump brought back memories of working in high tech environments where developers would come up with all kinds of nifty ideas but put absolutely no thought into how these ideas might actually work once human human beings got their hands on the product. In any event, the micropump seems exciting and I hope researchers work out the kinks, implementationwise, before they’re implanted.