Tag Archives: nerve cells

Carbon nanotubes to repair nerve fibres (cyborg brains?)

Can cyborg brains be far behind now that researchers are looking at ways to repair nerve fibers with carbon nanotubes (CNTs)? A June 26, 2017 news item on ScienceDaily describes the scheme using carbon nanotubes as a material for repairing nerve fibers,

Carbon nanotubes exhibit interesting characteristics rendering them particularly suited to the construction of special hybrid devices — consisting of biological issue and synthetic material — planned to re-establish connections between nerve cells, for instance at spinal level, lost on account of lesions or trauma. This is the result of a piece of research published on the scientific journal Nanomedicine: Nanotechnology, Biology, and Medicine conducted by a multi-disciplinary team comprising SISSA (International School for Advanced Studies), the University of Trieste, ELETTRA Sincrotrone and two Spanish institutions, Basque Foundation for Science and CIC BiomaGUNE. More specifically, researchers have investigated the possible effects on neurons of the interaction with carbon nanotubes. Scientists have proven that these nanomaterials may regulate the formation of synapses, specialized structures through which the nerve cells communicate, and modulate biological mechanisms, such as the growth of neurons, as part of a self-regulating process. This result, which shows the extent to which the integration between nerve cells and these synthetic structures is stable and efficient, highlights the great potentialities of carbon nanotubes as innovative materials capable of facilitating neuronal regeneration or in order to create a kind of artificial bridge between groups of neurons whose connection has been interrupted. In vivo testing has actually already begun.

The researchers have included a gorgeous image to illustrate their work,

Caption: Scientists have proven that these nanomaterials may regulate the formation of synapses, specialized structures through which the nerve cells communicate, and modulate biological mechanisms, such as the growth of neurons, as part of a self-regulating process. Credit: Pixabay

A June 26, 2017 SISSA press release (also on EurekAlert), which originated the news item, describes the work in more detail while explaining future research needs,

“Interface systems, or, more in general, neuronal prostheses, that enable an effective re-establishment of these connections are under active investigation” explain Laura Ballerini (SISSA) and Maurizio Prato (UniTS-CIC BiomaGUNE), coordinating the research project. “The perfect material to build these neural interfaces does not exist, yet the carbon nanotubes we are working on have already proved to have great potentialities. After all, nanomaterials currently represent our best hope for developing innovative strategies in the treatment of spinal cord injuries”. These nanomaterials are used both as scaffolds, a supportive framework for nerve cells, and as means of interfaces releasing those signals that empower nerve cells to communicate with each other.

Many aspects, however, still need to be addressed. Among them, the impact on neuronal physiology of the integration of these nanometric structures with the cell membrane. “Studying the interaction between these two elements is crucial, as it might also lead to some undesired effects, which we ought to exclude”. Laura Ballerini explains: “If, for example, the mere contact provoked a vertiginous rise in the number of synapses, these materials would be essentially unusable”. “This”, Maurizio Prato adds, “is precisely what we have investigated in this study where we used pure carbon nanotubes”.

The results of the research are extremely encouraging: “First of all we have proved that nanotubes do not interfere with the composition of lipids, of cholesterol in particular, which make up the cellular membrane in neurons. Membrane lipids play a very important role in the transmission of signals through the synapses. Nanotubes do not seem to influence this process, which is very important”.

There is more, however. The research has also highlighted the fact that the nerve cells growing on the substratum of nanotubes, thanks to this interaction, develop and reach maturity very quickly, eventually reaching a condition of biological homeostasis. “Nanotubes facilitate the full growth of neurons and the formation of new synapses. This growth, however, is not indiscriminate and unlimited since, as we proved, after a few weeks a physiological balance is attained. Having established the fact that this interaction is stable and efficient is an aspect of fundamental importance”. Maurizio Prato and Laura Ballerini conclude as follows: “We are proving that carbon nanotubes perform excellently in terms of duration, adaptability and mechanical compatibility with the tissue. Now we know that their interaction with the biological material, too, is efficient. Based on this evidence, we are already studying the in vivo application, and preliminary results appear to be quite promising also in terms of recovery of the lost neurological functions”.

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

Sculpting neurotransmission during synaptic development by 2D nanostructured interfaces by Niccolò Paolo Pampaloni, Denis Scaini, Fabio Perissinotto, Susanna Bosi, Maurizio Prato, Laura Ballerini. Nanomedicine: Nanotechnology, Biology and Medicine, DOI: http://dx.doi.org/10.1016/j.nano.2017.01.020 Published online: May 25, 2017

This paper is open access.

Bioelectronics: creating components that speak the body’s own language

This is work is still in its early stages but the idea that the body could be stimulated to release more of its own pain relievers is exciting. From a Nov. 2, 2016 news item on ScienceDaily,

With a microfabricated ion pump built from organic electronic components, ions can be sent to nerve or muscle cells at the speed of the nervous system and with a precision of a single cell. “Now we can start to develop components that speak the body’s own language,” says Daniel Simon, head of bioelectronics research at the Laboratory of Organic Electronics, Linköping University, Campus Norrköping.

A Nov. 2, 2016 Linköping University press release (also on EurekAlert), which originated the news item, discusses the research in more detail,

Our nerve and muscle cells send signals to each other using ions and molecules. Certain substances, such as the neurotransmitter GABA (gamma aminobutyric acid), are important signal substances throughout the central nervous system. Eighteen months ago, researchers at the Laboratory of Organic Electronics demonstrated an ion pump which researchers at the Karolinska Institutet could use to reduce the sensation of pain in awake, freely-moving rats. The ion pump delivered GABA directly to the rat´s spinal cord. The news that researchers could deliver the body’s own neurotransmitters was published in Science Advances and garnered intense interest all over the world.

The research group at the Laboratory of Organic Electronics has now achieved another major advance and developed a significantly smaller and more rapid ion pump that transmits signals nearly as rapidly as the cells themselves, and with a precision on the scale of an individual cell. …

“Our skilled doctoral students, Amanda Jonsson and Theresia Arbring Sjöström, have succeeded with the last important part of the puzzle in the development of the ion pump. When a signal passes between two synapses it takes 1-10 milliseconds, and we are now very close to the nervous system’s own speed,” says Magnus Berggren, professor of organic electronics and director of the Laboratory of Organic Electronics.

“We conclude that we have produced artificial nerves that can communicate seamlessly with the nervous system. After more than 10 years’ research we have finally got all the parts of the puzzle in place,” he says.

Amanda Jonsson, who together with Theresia Arbring Sjöström is principal author of the article in Science Advances, has developed the pain-alleviating ion pump as part of her doctoral studies. She proudly presents a glass disk with many of the new miniaturized ion pumps. Some pumps have only a single outlet, but others have six tiny point outlets.

“We can make them with several outlets, it’s just as easy as making one. And all of the outlets can be individually controlled. Previously we could only transport ions horizontally and from all outputs at the same time. Now, however, we can deliver the ions vertically, which makes the distance they have to be transported as short as a micrometre,” she explains.

All of the outputs of the ion pump can also be rapidly switched on or off with the aid of micrometre-sized ion diodes.

“The ions are released rapidly by an electrical signal, in the same way that the neurotransmitter is released in a synapse,” says Theresia Arbring Sjöström.

Organic electronic components have a major advantage here: they can conduct both ions and electricity. In this case, the material PEDOT:PSS enables the electrical signals to be converted to chemical signals that the body understands.

The ion diode has recently been developed, as has the material that forms the basis of the new rapid ion pump.

“The new material makes it possible to build with a precision and reliability not possible in previous versions of the ion pump,” says Daniel Simon.

The new ion pump has so far only been tested in the laboratory. The next step will be to test it with live cells and the researchers hope eventually to, for example alleviate pain, stop epileptic seizures, and reduce the symptoms of Parkinsons disease, using exactly the required dose at exactly the affected cells. Communication using the cell´s own language, and the cell´s own speed.

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

Chemical delivery array with millisecond neurotransmitter release by Amanda Jonsson, Theresia Arbring Sjöström, Klas Tybrandt, Magnus Berggren, and Daniel T. Simon. Science Advances  02 Nov 2016: Vol. 2, no. 11, e1601340 DOI: 10.1126/sciadv.1601340

This paper is open access.

Graphene and neurons in a UK-Italy-Spain collaboration

There’s been a lot of talk about using graphene-based implants in the brain due to the material’s flexibility along with its other properties. A step forward has been taking according to a Jan. 29, 2016 news item on phys.org,

Researchers have successfully demonstrated how it is possible to interface graphene – a two-dimensional form of carbon – with neurons, or nerve cells, while maintaining the integrity of these vital cells. The work may be used to build graphene-based electrodes that can safely be implanted in the brain, offering promise for the restoration of sensory functions for amputee or paralysed patients, or for individuals with motor disorders such as epilepsy or Parkinson’s disease.

A Jan. 29, 2016 Cambridge University press release (also on EurekAlert), which originated the news item, provides more detail,

Previously, other groups had shown that it is possible to use treated graphene to interact with neurons. However the signal to noise ratio from this interface was very low. By developing methods of working with untreated graphene, the researchers retained the material’s electrical conductivity, making it a significantly better electrode.

“For the first time we interfaced graphene to neurons directly,” said Professor Laura Ballerini of the University of Trieste in Italy. “We then tested the ability of neurons to generate electrical signals known to represent brain activities, and found that the neurons retained their neuronal signalling properties unaltered. This is the first functional study of neuronal synaptic activity using uncoated graphene based materials.”

Our understanding of the brain has increased to such a degree that by interfacing directly between the brain and the outside world we can now harness and control some of its functions. For instance, by measuring the brain’s electrical impulses, sensory functions can be recovered. This can be used to control robotic arms for amputee patients or any number of basic processes for paralysed patients – from speech to movement of objects in the world around them. Alternatively, by interfering with these electrical impulses, motor disorders (such as epilepsy or Parkinson’s) can start to be controlled.

Scientists have made this possible by developing electrodes that can be placed deep within the brain. These electrodes connect directly to neurons and transmit their electrical signals away from the body, allowing their meaning to be decoded.

However, the interface between neurons and electrodes has often been problematic: not only do the electrodes need to be highly sensitive to electrical impulses, but they need to be stable in the body without altering the tissue they measure.

Too often the modern electrodes used for this interface (based on tungsten or silicon) suffer from partial or complete loss of signal over time. This is often caused by the formation of scar tissue from the electrode insertion, which prevents the electrode from moving with the natural movements of the brain due to its rigid nature.

Graphene has been shown to be a promising material to solve these problems, because of its excellent conductivity, flexibility, biocompatibility and stability within the body.

Based on experiments conducted in rat brain cell cultures, the researchers found that untreated graphene electrodes interfaced well with neurons. By studying the neurons with electron microscopy and immunofluorescence the researchers found that they remained healthy, transmitting normal electric impulses and, importantly, none of the adverse reactions which lead to the damaging scar tissue were seen.

According to the researchers, this is the first step towards using pristine graphene-based materials as an electrode for a neuro-interface. In future, the researchers will investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons, and whether tuning the material properties of graphene might alter the synapses and neuronal excitability in new and unique ways. “Hopefully this will pave the way for better deep brain implants to both harness and control the brain, with higher sensitivity and fewer unwanted side effects,” said Ballerini.

“We are currently involved in frontline research in graphene technology towards biomedical applications,” said Professor Maurizio Prato from the University of Trieste. “In this scenario, the development and translation in neurology of graphene-based high-performance biodevices requires the exploration of the interactions between graphene nano- and micro-sheets with the sophisticated signalling machinery of nerve cells. Our work is only a first step in that direction.”

“These initial results show how we are just at the tip of the iceberg when it comes to the potential of graphene and related materials in bio-applications and medicine,” said Professor Andrea Ferrari, Director of the Cambridge Graphene Centre. “The expertise developed at the Cambridge Graphene Centre allows us to produce large quantities of pristine material in solution, and this study proves the compatibility of our process with neuro-interfaces.”

The research was funded by the Graphene Flagship [emphasis mine],  a European initiative which promotes a collaborative approach to research with an aim of helping to translate graphene out of the academic laboratory, through local industry and into society.

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

Graphene-Based Interfaces Do Not Alter Target Nerve Cells by Alessandra Fabbro, Denis Scaini, Verónica León, Ester Vázquez, Giada Cellot, Giulia Privitera, Lucia Lombardi, Felice Torrisi, Flavia Tomarchio, Francesco Bonaccorso, Susanna Bosi, Andrea C. Ferrari, Laura Ballerini, and Maurizio Prato. ACS Nano, 2016, 10 (1), pp 615–623 DOI: 10.1021/acsnano.5b05647 Publication Date (Web): December 23, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

There are a couple things I found a bit odd about this project. First, all of the funding is from the Graphene Flagship initiative. I was expecting to see at least some funding from the European Union’s other mega-sized science initiative, the Human Brain Project. Second, there was no mention of Spain nor were there any quotes from the Spanish researchers. For the record, the Spanish institutions represented were: University of Castilla-La Mancha, Carbon Nanobiotechnology Laboratory, and the Basque Foundation for Science.

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.

Nanocellulose as scaffolding for nerve cells

Swedish scientists have announced success with growing nerve cells using nanocellulose as the scaffolding. From the March 19, 2012 news item on Naowerk,

Researchers from Chalmers and the University of Gothenburg have shown that nanocellulose stimulates the formation of neural networks. This is the first step toward creating a three-dimensional model of the brain. Such a model could elevate brain research to totally new levels, with regard to Alzheimer’s disease and Parkinson’s disease, for example.

“This has been a great challenge,” says Paul Gatenholm, Professor of Biopolymer Technology at Chalmers.?Until recently the cells were dying after a while, since we weren’t able to get them to adhere to the scaffold. But after many experiments we discovered a method to get them to attach to the scaffold by making it more positively charged. Now we have a stable method for cultivating nerve cells on nanocellulose.”

When the nerve cells finally attached to the scaffold they began to develop and generate contacts with one another, so-called synapses. A neural network of hundreds of cells was produced. The researchers can now use electrical impulses and chemical signal substances to generate nerve impulses, that spread through the network in much the same way as they do in the brain. They can also study how nerve cells react with other molecules, such as pharmaceuticals.

I found the original March 19, 2012 press release  and an image on the University of Chalmers website,

Nerve cells growing on a three-dimensional nanocellulose scaffold. One of the applications the research group would like to study is destruction of synapses between nerve cells, which is one of the earliest signs of Alzheimer’s disease. Synapses are the connections between nerve cells. In the image, the functioning synapses are yellow and the red spots show where synapses have been destroyed. Illustration: Philip Krantz, Chalmers

This latest research from Gatenholm and his team will be presented at the American Chemical Society annual meeting in San Diego, March 25, 2012.

The research team from Chalmers University and its partners are working on other applications for nanocellulose including one for artificial ears. From the Chalmers University Jan. 22, 2012 press release,

As the first group in the world, researchers from Chalmers will build up body parts using nanocellulose and the body’s own cells. Funding will be from the European network for nanomedicine, EuroNanoMed.

Professor Paul Gatenholm at Chalmers is leading and co-ordinating this European research programme, which will construct an outer ear using nanocellulose and a mixture of the patient’s own cartilage cells and stem cells.

Previously, Paul Gatenholm and his colleagues succeeded, in close co-operation with Sahlgrenska University Hospital, in developing artificial blood vessels using nanocellulose, where small bacteria “spin” the cellulose.

In the new programme , the researchers will build up a three-dimensional nanocellulose network that is an exact copy of the patient’s healthy outer ear and construct an exact mirror image of the ear. It will have sufficient mechanical stability for it to be used as a bioreactor, which means that the patient’s own cartilage and stem cells can be cultivated directly inside the body or on the patient, in this case on the head. [Presumably the patient has one ear that is healthy and the researchers are attempting to repair or replace an unhealthy ear on the other side of the head.]

As for the Swedish perspective on nanocellulose (from the 2010 press release),

Cellulose-based material is of strategic significance to Sweden and materials science is one of Chalmers eight areas of advance. Biopolymers are highly interesting as they are renewable and could be of major significance in the development of future materials.

Further research into using the forest as a resource for new materials is continuing at Chalmers within the new research programme that is being built up with different research groups at Chalmers and Swerea – IVF. The programme is part of the Wallenberg Wood Science Center, which is being run jointly by the Royal Institute of Technology in Stockholm and Chalmers under the leadership of Professor Lars Berglund at the Royal Institute of Technology.

The 2012 press release announcing the work on nerve cells had this about nanocellulose,

Nanocellulose is a material that consists of nanosized cellulose fibers. Typical dimensions are widths of 5 to 20 nanometers and lengths of up to 2,000 nanometers. Nanocellulose can be produced by bacteria that spin a close-meshed structure of cellulose fibers. It can also be isolated from wood pulp through processing in a high-pressure homogenizer.

I last wrote about the Swedes and nanocellulose in a Feb. 15, 2012 posting about recovering it (nanocellulose) from wood-based sludge.

As for anyone interested in the Canadian scene, there is an article by David Manly in the Jan.-Feb. 2012 issue of Canadian Biomass Magazine that focuses largely on economic impacts and value-added products as they pertain to nanocellulose manufacturing production in Canada. You can also search this blog as I have covered the nanocellulose story in Canada and elsewhere as extensively as I can.