Category Archives: medicine

Controlling neurons with light: no batteries or wires needed

Caption: Wireless and battery-free implant with advanced control over targeted neuron groups. Credit: Philipp Gutruf

This January 2, 2019 news item on ScienceDaily describes the object seen in the above and describes the problem it’s designed to solve,

University of Arizona biomedical engineering professor Philipp Gutruf is first author on the paper Fully implantable, optoelectronic systems for battery-free, multimodal operation in neuroscience research, published in Nature Electronics.

Optogenetics is a biological technique that uses light to turn specific neuron groups in the brain on or off. For example, researchers might use optogenetic stimulation to restore movement in case of paralysis or, in the future, to turn off the areas of the brain or spine that cause pain, eliminating the need for — and the increasing dependence on — opioids and other painkillers.

“We’re making these tools to understand how different parts of the brain work,” Gutruf said. “The advantage with optogenetics is that you have cell specificity: You can target specific groups of neurons and investigate their function and relation in the context of the whole brain.”

In optogenetics, researchers load specific neurons with proteins called opsins, which convert light to electrical potentials that make up the function of a neuron. When a researcher shines light on an area of the brain, it activates only the opsin-loaded neurons.

The first iterations of optogenetics involved sending light to the brain through optical fibers, which meant that test subjects were physically tethered to a control station. Researchers went on to develop a battery-free technique using wireless electronics, which meant subjects could move freely.

But these devices still came with their own limitations — they were bulky and often attached visibly outside the skull, they didn’t allow for precise control of the light’s frequency or intensity, and they could only stimulate one area of the brain at a time.

A Dec. 21, 2018 University of Azrizona news release (published Jan. 2, 2019 on EurekAlert), which originated the news item, discusses the work in more detail,

“With this research, we went two to three steps further,” Gutruf said. “We were able to implement digital control over intensity and frequency of the light being emitted, and the devices are very miniaturized, so they can be implanted under the scalp. We can also independently stimulate multiple places in the brain of the same subject, which also wasn’t possible before.”

The ability to control the light’s intensity is critical because it allows researchers to control exactly how much of the brain the light is affecting — the brighter the light, the farther it will reach. In addition, controlling the light’s intensity means controlling the heat generated by the light sources, and avoiding the accidental activation of neurons that are activated by heat.

The wireless, battery-free implants are powered by external oscillating magnetic fields, and, despite their advanced capabilities, are not significantly larger or heavier than past versions. In addition, a new antenna design has eliminated a problem faced by past versions of optogenetic devices, in which the strength of the signal being transmitted to the device varied depending on the angle of the brain: A subject would turn its head and the signal would weaken.

“This system has two antennas in one enclosure, which we switch the signal back and forth very rapidly so we can power the implant at any orientation,” Gutruf said. “In the future, this technique could provide battery-free implants that provide uninterrupted stimulation without the need to remove or replace the device, resulting in less invasive procedures than current pacemaker or stimulation techniques.”

Devices are implanted with a simple surgical procedure similar to surgeries in which humans are fitted with neurostimulators, or “brain pacemakers.” They cause no adverse effects to subjects, and their functionality doesn’t degrade in the body over time. This could have implications for medical devices like pacemakers, which currently need to be replaced every five to 15 years.

The paper also demonstrated that animals implanted with these devices can be safely imaged with computer tomography, or CT, and magnetic resonance imaging, or MRI, which allow for advanced insights into clinically relevant parameters such as the state of bone and tissue and the placement of the device.

This image of a combined MRI (magnetic resonance image) and CT (computer tomography) scan bookends, more or less, the picture of the device which headed this piece,

Combined image analysis with MRI and CT results superimposed on a 3D rendering of the animal implanted with the programmable bilateral multi µ-ILED device. Courtesy: University of Arizona

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

Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research by Philipp Gutruf, Vaishnavi Krishnamurthi, Abraham Vázquez-Guardado, Zhaoqian Xie, Anthony Banks, Chun-Ju Su, Yeshou Xu, Chad R. Haney, Emily A. Waters, Irawati Kandela, Siddharth R. Krishnan, Tyler Ray, John P. Leshock, Yonggang Huang, Debashis Chanda, & John A. Rogers. Nature Electronics volume 1, pages652–660 (2018) DOI: https://doi.org/10.1038/s41928-018-0175-0 Published 13 December 2018

This paper is behind a paywall.

Tapping into wound healing by harnessing the natural healing process

If you’re imagining an enhanced chakra balancing experience or more efficient digestion of your vitamin supplements, you will be a little disappointed in this latest news from the Imperial College of London (ICL). On the other hand, if you have damaged tissue, this discovery could make your recovery much easier. From a January 7, 2019 news item on phys.org,

Materials are widely used to help heal wounds: Collagen sponges help treat burns and pressure sores, and scaffold-like implants are used to repair bones. However, the process of tissue repair changes over time, so scientists are developing biomaterials that interact with tissues as healing takes place

Now, Dr. Ben Almquist and his team at Imperial College London have created a new molecule that could change the way traditional materials work with the body. Known as traction force-activated payloads (TrAPs), their method lets materials talk to the body’s natural repair systems to drive healing.

The researchers say incorporating TrAPs into existing medical materials could revolutionise the way injuries are treated. Dr. Almquist, from Imperial’s Department of Bioengineering, said: “Our technology could help launch a new generation of materials that actively work with tissues to drive healing.”

A January 7, 2019 ICL press release (also on EurekAlert) by Caroline Brogan, which originated the news item, expands on the theme,

After an injury, cells ‘crawl’ through the collagen ‘scaffolds’ found in wounds, like spiders navigating webs. As they move, they pull on the scaffold, which activates hidden healing proteins that begin to repair injured tissue.

The researchers in the study designed TrAPs as a way to recreate this natural healing method. They folded the DNA segments into three-dimensional shapes known as aptamers that cling tightly to proteins. Then, they attached a customisable ‘handle’ that cells can grab onto on one end, before attaching the opposite end to a scaffold such as collagen.

During laboratory testing of their technique, they found that cells pulled on the TrAPs as they crawled through the collagen scaffolds. The pulling made the TrAPs unravel like shoelaces to reveal and activate the healing proteins. These proteins instruct the healing cells to grow and multiply

The researchers also found that by changing the cellular ‘handle’, they can change which type of cell can grab hold and pull, letting them tailor TrAPs to release specific therapeutic proteins based on which cells are present at a given point in time. In doing so, the TrAPs produce materials that can smartly interact with the correct type of cell at the correct time during wound repair.

This is the first time scientists have activated healing proteins using differing cell types in man-made materials. The technique mimics healing methods found in nature. Dr Almquist said: “Creatures from sea sponges to humans use cell movement to activate healing. Our approach mimics this by using the different cell varieties in wounds to drive healing.””

From lab to humans

This approach is adaptable to different cell types, so could be used in a variety of injuries such as fractured bones, scar tissue after heart attacks, and damaged nerves. New techniques are also desperately needed for patients whose wounds won’t heal despite current interventions, like diabetic foot ulcers, which are the leading cause of non-traumatic lower leg amputations.

TrAPs are relatively straightforward to create and are fully man-made, meaning they are easily recreated in different labs and can be scaled up to industrial quantities. Their adaptability also means they could help scientists create new methods for laboratory studies of diseases, stem cells, and tissue development.

Aptamers are currently used as drugs, meaning they are already proven safe and optimised for clinical use. Because TrAPs take advantage of aptamers that are safe for humans, they may be able to take a shorter path to the clinic than methods that start from ground zero.

Dr Almquist said: “TrAPs provide a flexible method of actively communicating with wounds, as well as key instructions when and where they are needed. This intelligent healing is useful during every phase of the healing process, has the potential to increase the body’s chance to recover, and has far-reaching uses on many different types of wounds. This technology could serve as a conductor of wound repair, orchestrating different cells over time to work together to heal damaged tissues.”

The researchers have made available an image and a video abstract illustrating their work,

TrAPs could harness the body’s natural healing powers to repair bone. Courtesy: Imperial College of London

By the way, the video was produced by www.animateyour.science (based in Adelaide, Australia) and they have a very interesting About page,

Our story

Your research is brilliant and novel. I’m sure of it. You might even be a pioneer in your field. But ask yourself honestly, is it enough? Is it truly enough to make a difference in the world?
 
My name is Tullio Rossi, and I founded Animate Your Science on my quest to make a positive impact on society through science.
 
During my Ph.D., I found that my peer-reviewed paper alone wasn’t cutting it. If I wanted to reach my peers, let alone the general public, I needed to communicate my findings in a fun and imaginative way.
 
This realization changed everything and inspired me to create “Lost at Sea,” an award-winning video that reached the hearts and minds of thousands of people.
 
The success of this first video blew my mind. And I got to thinking, maybe other scientists are lost at sea, so to speak. Maybe others want to reach the masses with their research, but just don’t know where to start.
 
This was the day Animate Your Science was born.

Why we do it

What we really want to do is bring science into society. That’s the true value of this company and the reason we believe in it.

We love science but we believe that, if not communicated properly, science is of limited use to society.​
 
As scientists, it’s our privilege and duty to unearth these revelations and package them in a way that appeals to our peers as well as the general public.

Getting back to TrAPS, here’s a link to and a citation for the paper,

Biologically Inspired, Cell‐Selective Release of Aptamer‐Trapped Growth Factors by Traction Forces by Anna Stejskalová, Nuria Oliva, Frances J. England, Benjamin D. Almquist. Advanced Materials DOI: https://doi.org/10.1002/adma.201806380 First published: 07 January 2019

This paper is open access.

Ouchies no more! Not from bandages, anyway.

An adhesive that US and Chinese scientists have developed shows great promise not just for bandages but wearable robotics too. From a December 14, 2018 news item on Nanowerk,

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Xi’an Jiaotong University in China have developed a new type of adhesive that can strongly adhere wet materials — such as hydrogel and living tissue — and be easily detached with a specific frequency of light.

The adhesives could be used to attach and painlessly detach wound dressings, transdermal drug delivery devices, and wearable robotics.

A December 18, 2018 SEAS news release by Leah Burrows (also on EurekAlert but published Dec. 14, 2018), which originated the news item, delves further,

“Strong adhesion usually requires covalent bonds, physical interactions, or a combination of both,” said Yang Gao, first author of the paper and researcher at Xi’an Jiaotong University. “Adhesion through covalent bonds is hard to remove and adhesion through physical interactions usually requires solvents, which can be time-consuming and environmentally harmful. Our method of using light to trigger detachment is non-invasive and painless.”

The adhesive uses an aqueous solution of polymer chains spread between two, non-sticky materials — like jam between two slices of bread. On their own, the two materials adhere poorly together but the polymer chains act as a molecular suture, stitching the two materials together by forming a network with the two preexisting polymer networks. This process is known as topological entanglement.

When exposed to ultra-violet light, the network of stitches dissolves, separating the two materials.

The researchers, led by Zhigang Suo, the Allen E. and Marilyn M. Puckett Professor of Mechanics and Materials at SEAS, tested adhesion and detachment on a range of materials, sticking together hydrogels; hydrogels and organic tissue; elastomers; hydrogels and elastomers; and hydrogels and inorganic solids.

“Our strategy works across a range of materials and may enable broad applications,” said Kangling Wu, co-lead author and researcher at Xi’an Jiaotong University in China.
While the researchers focused on using UV light to trigger detachment, their work suggests the possibility that the stitching polymer could detach with near-infrared light, a feature which could be applied to a range of new medical procedures.

“In nature, wet materials don’t like to adhere together,” said Suo. “We have discovered a general approach to overcome this challenge. Our molecular sutures can strongly adhere wet materials together. Furthermore, the strong adhesion can be made permanent, transient, or detachable on demand, in response to a cue. So, as we see it, nature is full of loopholes, waiting to be stitched.”

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

Photodetachable Adhesion by Yang Gao, Kangling Wu, Zhigang Suo. https://doi.org/10.1002/adma.201806948 First published: 14 December 2018

This paper is behind a paywall.

Better anti-parasitic medicine delivery with chitosan-based nanocapsules

I mage: The common liver fluke which can cause fascioliasis. Credit: Wikimedia creative commons Courtesy: Leeds University

It looks like a pair of lips to me but, according to a December 12, 2018 news item on Nanowerk, this liver fluke heralds a flatworm infection is a serious health problem,

An international team, led by Professor Francisco Goycoolea from the University of Leeds [UK] and Dr Claudio Salomon from the Universidad Nacional de Rosario, Argentina, and in collaboration with colleagues at the University of Münster, Germany, have developed a novel pharmaceutical formulation to administer triclabendazole – an anti-parasitic drug used to treat a type of flatworm infection – in billions of tiny capsules.

The World Health Organisation estimates that 2.4 million people are infected with fascioliasis, the disease caused by flatworms and treated with triclabendazole.

A December 12, 2018 University of Leeds  press release (also on EurekAlert), which originated the news item,

Anti-parasitic drugs do not become effective until they dissolve and are absorbed. Traditionally, these medicines are highly insoluble and this limits their therapeutic effect.
In a bid to overcome this limitation and accomplish the new formulation, the team used “soft” nanotechnology and nanomedicine approaches, which utilises the self-assembly properties of organic nanostructures and uses techniques in which components, such as polymers and surfactants in solution, play key roles.

Their formulation produces capsules that are less than one micron in size – the diameter of a human hair is roughly 75 microns. These tiny capsules are loaded with triclabendazole and then bundled together to deliver the required dose.

The team used chitosan, a naturally-occurring sugar polymer found in the exoskeleton of shellfish and the cell walls of certain fungi, to coat the oil-core of capsules and bind the drug together, while stabilising the capsule and helping to preserve it.
In its nanocapsule form, the drug would be 100 times more soluble than its current tablet form.

Professor Goycoolea, from the School of Food Science and Nutrition at Leeds, said: “Solubility is critical challenge for effective anti-parasite medicine. We looked to tackle this problem at the particle level. Triclabendazole taken as a dose made up of billions of tiny capsules would mean the medicine would be more efficiently and quickly absorbed

“Through the use of nanocapsules and nanoemulsions, drug efficiency can be enhanced and new solutions can be considered for the best ways to target medicine delivery.”
Dr Salomon said: “To date, this is the first report on triclabendazole nanoencapsulation and we believe this type of formulation could be applied to other anti-parasitic drugs as well. But more research is needed to ensure this new pharmaceutical formulation of the drug does not diminish the anti-parasitic effect. Our ongoing research is working to answer this very question.”

Although there have been cases of fascioliasis in more than 70 countries worldwide, with increasing reports from Europe and the Americas, it is considered a neglected disease, as it does not receive much attention and often goes untreated.
Symptoms of the disease when it reaches the chronic phase include intermittent pain, jaundice and anaemia. Patients can also experience hardening of the liver in the case of long-term inflammation.

Because of the highly insoluble nature of anti-parasitic drugs, they need to be administered in very high dosages to ensure enough of the active ingredient is absorbed. This is particularly problematic when treating children for parasites. Tablets needs to be divided into smaller pieces to adjust the dosage and make swallowing easier, but this can cause side effects due to incorrect dosage.

The team’s technique to formulate triclabendazole into nanocapsules, published today [Dec. 12, 2018] in the journal PLOS ONE, would also allow for lower doses to be administered. s

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

Chitosan-based nanodelivery systems applied to the development of novel triclabendazole formulations by Daniel Real, Stefan Hoffmann, Darío Leonardi, Claudio Salomon, Francisco M. Goycoolea. PLOS DOI https://doi.org/10.1371/journal.pone.0207625 Published: December 12, 2018

This paper is open access. BTW, I loved the title for the press release (Helping the anti-parasitic medicine go down) for its reference to the song, A spoonful of sugar helps the medicine go down, in the 1964 film musical, Mary Poppins, and the shout out for the sort of sequel, Mary Poppins Returns, released on Dec. 19, 2018.

Membrane stretching as a new transport mechanism for nanomaterials

This work comes from Catalonia, Spain by way of a collaboration between Chinese, German, and, of course, Spanish scientists. From a December 12, 2018 Universitat Rovira i Virgili press release (also on EurekAlert),

Increasing awareness of bioeffects and toxicity of nanomaterials interacting with cells puts in focus the mechanisms by which nanomaterials can cross lipid membranes. Apart from well-discussed energy-dependent endocytosis for large objects and passive diffusion through membranes by solute molecules, there can exist other transport mechanisms based on physical principles. Based on this hypothesis, the team of theoretical physics at Universitat Rovira i Virgili in Tarragona, led by Dr. Vladimir Baulin, designed a research project to investigate the interaction between nanotube and lipid membranes. In computer simulations, the researchers studied what they call a “model bilayer”, composed only by one type of lipids. Based on their calculations, the team of Dr. Baulin observed that ultra -short nanotube (10nm length) can insert perpendicularly to the lipid bilayer core.

They observed that these nanotubes stay trapped in the cell membrane, as commonly accepted by the scientific community. But a surprise appears when they stretched their model cell membrane, then inserted nanotubes which were trapped in the bilayer, suddenly started to escape from the bilayer on both sides. This means that it is possible to control the transport of nanomaterial across a cell membrane by tuning the membrane tension.

This is where Dr. Baulin contacted Dr. Jean-Baptiste Fleury at the Saarland University (Germany) to confirm this mechanism and to study experimentally this tension-mediated transport phenomena. Dr. Fleury and his team, designed a microfluidic experiment with a well-controlled phospholipid bilayer, an experimental model for cell membranes and added ultra-small carbon nanotubes (10nm in length) in solution. The nanotubes had an adsorbed lipid monolayer that guarantees their stable dispersion and prevent their clustering. Using a combination of optical fluorescent microscopy and electrophysiological measurements, the team of Dr. Fleury could follow individual nanotube crossing a bilayer and unravel their pathway on a molecular level. And as predicted by the simulations, they observed that nanotubes inserted into the bilayer by dissolving their lipid coating into the artificial membrane. When a tension of 4mN/m was applied to the bilayer, nanotubes spontaneously escaped the bilayer just in few milliseconds, while at lower tensions nanotubes remain trapped inside the membrane.

This discovery of translocation of tiny nanotubes through barriers protecting cells, i.e. lipid bilayer, may raise concerns about safety of nanomaterials for public health and suggest new mechanical mechanisms to control the drug delivery.

Caption: Nanotubes trapped inside the membrane. Credit: © URV

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

Tension-Induced Translocation of an Ultrashort Carbon Nanotube through a Phospholipid Bilayer by Yachong Guo, Marco Werner, Ralf Seemann, Vladimir A. Baulin, and Jean-Baptiste Fleury. ACS Nano, Article ASAP DOI: 10.1021/acsnano.8b04657 Publication Date (Web): November 19, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Cellulose biosensor heralds new bioimaging approach to tissue engineering

I keep an eye on how nanocellulose is being used in various applications and I’m not sure that this cellulose biosensor quite fits the bill as nanocellulose, nonetheless, it’s interesting and that’s enough for me. From a December 12, 2018 Sechenov University (Russia) press release on EurekAlert,

I.M. Sechenov First Moscow State Medical University teamed up together with Irish colleagues to develop a new imaging approach for tissue engineering. The team produced so-called ‘hybrid biosensor’ scaffold materials, which are based on cellulose matrices labeled with pH- and calcium-sensitive fluorescent proteins. These materials enable visualization of the metabolism and other important biomarkers in the engineered artificial tissues by microscopy. The results of the work were published in the Acta Biomaterialia journal.
The success of tissue engineering is based on the use of scaffold matrices – materials that support the viability and direct the growth of cells, tissues, and organoids. Scaffolds are important for basic and applied biomedical research, tissue engineering and regenerative medicine, and are promising for development of new therapeutics. However, the ability ‘to see’ what happens within the scaffolds during the tissue growth poses a significant research challenge

“We developed a new approach allowing visualization of scaffold-grown tissue and cells by using labeling with biosensor fluorescent proteins. Due to the high specificity of labeling and the use of fluorescence microscopy FLIM, we can quantify changes in pH and calcium in the vicinity of cells,” says Dr. Ruslan Dmitriev, Group Leader at the University College Cork and the Institute for Regenerative Medicine (I.M. Sechenov First Moscow State Medical University).
To achieve the specific labeling of cellulose matrices, researchers used well-known cellulose-binding proteins. The use of extracellular pH- and calcium-sensitive biosensors allow for analysis of cell metabolism: indeed, the extracellular acidification is directly associated with the balance of cell energy production pathways and the glycolytic flux (release of lactate). It is also a frequent hallmark of cancer and transformed cell types. On the other hand, calcium plays a key role in the extra- and intracellular signaling affecting cell growth and differentiation.

The approach was tested on different types of cellulose matrices (bacterial and produced from decellularised plant tissues) using 3D culture of human colon cancer cells and stem-cell derived mouse small intestinal organoids. The scaffolds informed on changes in the extracellular acidification and were used together with the analysis of real-time oxygenation of intestinal organoids. The resulting data can be presented in the form of colour maps, corresponding to the areas of cell growth within different microenvironments.

“Our results open new prospects in the imaging of tissue-engineered constructs for regenerative medicine. They enable deeper understanding of tissue metabolism in 3D and are also highly promising for commercialisation,” concludes Dr. Dmitriev.

The researchers have provided an image to illustrate their work,

Caption: A 3D reconstruction of a cellulose matrix stained with a pH-sensitive biosensor. Credit: Dr. R. Dmitriev

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

Cellulose-based scaffolds for fluorescence lifetime imaging-assisted tissue engineering by Neil O’Donnell, Irina A. Okkelman, Peter Timashev, Tatyana I.Gromovykh, Dmitri B. Papkovsky, Ruslan I.Dmitriev. Acta Biomaterialia Volume 80, 15 October 2018, Pages 85-96 DOI: https://doi.org/10.1016/j.actbio.2018.09.034


This paper is behind a paywall.

Bandage with nanogenerator promotes healing

This bandage not only heals wounds (on rats) much faster; it’s cheap, according to a November 29, 2018 news item on Nanowerk,

A new, low-cost wound dressing developed by University of Wisconsin-Madison engineers could dramatically speed up healing in a surprising way.

The method leverages energy generated from a patient’s own body motions to apply gentle electrical pulses at the site of an injury.

In rodent tests, the dressings reduced healing times to a mere three days compared to nearly two weeks for the normal healing process.

“We were surprised to see such a fast recovery rate,” says Xudong Wang, a professor of materials science and engineering at UW-Madison. “We suspected that the devices would produce some effect, but the magnitude was much more than we expected.”

A November 29, 2018 University of Wisconsin-Madison news release (also on EurekAlert) by Sam Million-Weaver, which originated the news item, expands on the theme,

Researchers have known for several decades that electricity can be beneficial for skin healing, but most electrotherapy units in use today require bulky electrical equipment and complicated wiring to deliver powerful jolts of electricity.

“Acute and chronic wounds represent a substantial burden in healthcare worldwide,” says collaborator Angela Gibson, professor of surgery at UW-Madison and a burn surgeon and director of wound healing services at UW Health. “The use of electrical stimulation in wound healing is uncommon.”

In contrast with existing methods, the new dressing is much more straightforward.

“Our device is as convenient as a bandage you put on your skin,” says Wang.

The new dressings consist of small electrodes for the injury site that are linked to a band holding energy-harvesting units called nanogenerators, which are looped around a wearer’s torso. The natural expansion and contraction of the wearer’s ribcage during breathing powers the nanogenerators, which deliver low-intensity electric pulses.

“The nature of these electrical pulses is similar to the way the body generates an internal electric field,” says Wang.

And, those low-power pulses won’t harm healthy tissue like traditional, high-power electrotherapy devices might.

In fact, the researchers showed that exposing cells to high-energy electrical pulses caused them to produce almost five times more reactive oxygen species — major risk factors for cancer and cellular aging — than did cells that were exposed to the nanogenerators.

Also a boon to healing: They determined that the low-power pulses boosted viability for a type of skin cell called fibroblasts, and exposure to the nanogenerator’s pulses encouraged fibroblasts to line up (a crucial step in wound healing) and produce more biochemical substances that promote tissue growth.

“These findings are very exciting,” says collaborator Weibo Cai, a professor of radiology at UW-Madison. “The detailed mechanisms will still need to be elucidated in future work.”

In that vein, the researchers aim to tease out precisely how the gentle pulses aid in healing. The scientists also plan to test the devices on pig skin, which closely mimics human tissue.

And, they are working to give the nanogenerators additional capabilities–tweaking their structure to allow for energy harvesting from small imperceptible twitches in the skin or the thrumming pulse of a heartbeat.

“The impressive results in this study represent an exciting new spin on electrical stimulation for many different wound types, given the simplicity of the design,” says Gibson, who will collaborate with the team to confirm the reproducibility of these results in human skin models.

If the team is successful, the devices could help solve a major challenge for modern medicine.

“We think our nanogenerator could be the most effective electrical stimulation approach for many therapeutic purposes,” says Wang.

And because the nanogenerators consist of relatively common materials, price won’t be an issue.

“I don’t think the cost will be much more than a regular bandage,” says Wang. “The device in itself is very simple and convenient to fabricate.”

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

Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable Nanogenerators by Yin Long, Hao Wei, Jun Li, Guang Yao, Bo Yu, Dalong Ni, Angela LF Gibson, Xiaoli Lan, Yadong Jiang, Weibo Cai, and Xudong Wang. ACS Nano, Article ASAP DOI: 10.1021/acsnano.8b07038 Publication Date (Web): November 29, 2018

Copyright © 2018 American Chemical Society

This paper is open access.

I assume it will be a while before there are human clinical trials.

Non-viral ocular gene therapy with gold nanoparticles and femtosecond lasers

I love the stylistic choice the writer made (pay special attention to the second paragraph) when producing this November 19, 2018 Polytechnique Montréal news release (also on EurekAlert),

A scientific breakthrough by Professor Michel Meunier of Polytechnique Montréal and his collaborators offers hope for people with glaucoma, retinitis or macular degeneration.

In January 2009, the life of engineer Michel Meunier, a professor at Polytechnique Montréal, changed dramatically. Like others, he had observed that the extremely short pulse of a femtosecond laser (0.000000000000001 second) could make nanometre-sized holes appear in silicon when it was covered by gold nanoparticles. But this researcher, recognized internationally for his skills in laser and nanotechnology, decided to go a step further with what was then just a laboratory curiosity. He wondered if it was possible to go from silicon to living matter, from inorganic to organic. Could the gold nanoparticles and the femtosecond laser, this “light scalpel,” reproduce the same phenomenon with living cells?

A very pretty image illustrating the work,

Caption: Gold nanoparticles, which act like “nanolenses,” concentrate the energy produced by the extremely short pulse of a femtosecond laser to create a nanoscale incision on the surface of the eye’s retina cells. This technology, which preserves cell integrity, can be used to effectively inject drugs or genes into specific areas of the eye, offering new hope to people with glaucoma, retinitis or macular degeneration. Credit and Copyright: Polytechnique Montréal

The news release goes on to describe the technology in more detail,

Professor Meunier started working on cells in vitro in his Polytechnique laboratory. The challenge was to make a nanometric incision in the cells’ extracellular membrane without damaging it. Using gold nanoparticles that acted as “nanolenses,” Professor Meunier realized that it was possible to concentrate the light energy coming from the laser at a wavelength of 800 nanometres. Since there is very little energy absorption by the cells at this wavelength, their integrity is preserved. Mission accomplished!

Based on this finding, Professor Meunier decided to work on cells in vivo, cells that are part of a complex living cell structure, such as the eye for example.

The eye and the light scalpel

In April 2012, Professor Meunier met Przemyslaw Sapieha, an internationally renowned eye specialist, particularly recognized for his work on the retina. “Mike”, as he goes by, is a professor in the Department of Ophthalmology at Université de Montréal and a researcher at Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Est-de-l’Île-de-Montréal. He immediately saw the potential of this new technology and everything that could be done in the eye if you could block the ripple effect that occurs following a trigger that leads to glaucoma or macular degeneration, for example, by injecting drugs, proteins or even genes.

Using a femtosecond laser to treat the eye–a highly specialized and fragile organ–is very complex, however. The eye is part of the central nervous system, and therefore many of the cells or families of cells that compose it are neurons. And when a neuron dies, it does not regenerate like other cells do. Mike Sapieha’s first task was therefore to ensure that a femtosecond laser could be used on one or several neurons without affecting them. This is what is referred to as “proof of concept.”

Proof of concept

Mike and Michel called on biochemistry researcher Ariel Wilson, an expert in eye structures and vision mechanisms, as well as Professor Santiago Costantino and his team from the Department of Ophthalmology at Université de Montréal and the CIUSSS de l’Est-de-l’Île-de-Montréal for their expertise in biophotonics. The team first decided to work on healthy cells, because they are better understood than sick cells. They injected gold nanoparticles combined with antibodies to target specific neuronal cells in the eye, and then waited for the nanoparticles to settle around the various neurons or families of neurons, such as the retina. Following the bright flash generated by the femtosecond laser, the expected phenomenon occurred: small holes appeared in the cells of the eye’s retina, making it possible to effectively inject drugs or genes in specific areas of the eye. It was another victory for Michel Meunier and his collaborators, with these conclusive results now opening the path to new treatments.

The key feature of the technology developed by the researchers from Polytechnique and CIUSSS de l’Est-de-l’Île-de-Montréal is its extreme precision. With the use of functionalized gold nanoparticles, the light scalpel makes it possible to precisely locate the family of cells where the doctor will have to intervene.

Having successfully demonstrated proof of concept, Professor Meunier and his team filed a patent application in the United States. This tremendous work was also the subject of a paper reviewed by an impressive reading committee and published in the renowned journal Nano Letters in October 2018.

While there is still a lot of research to be done–at least 10 years’ worth, first on animals and then on humans–this technology could make all the difference in an aging population suffering from eye deterioration for which there are still no effective long-term treatments. It also has the advantage of avoiding the use of viruses commonly employed in gene therapy. These researchers are looking at applications of this technology in all eye diseases, but more particularly in glaucoma, retinitis and macular degeneration.

This light scalpel is unprecedented.

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

In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated Gold Nanoparticles by Ariel M. Wilson, Javier Mazzaferri, Éric Bergeron, Sergiy Patskovsky, Paule Marcoux-Valiquette, Santiago Costantino, Przemyslaw Sapieha, Michel Meunier. Nano Lett.201818116981-6988 DOI: https://doi.org/10.1021/acs.nanolett.8b02896 Publication Date: October 4, 2018  Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Lifesaving moths and nanomagnets

Rice University bioengineers use a magnetic field to activate nanoparticle-attached baculoviruses in a tissue. The viruses, which normally infect alfalfa looper moths, are modified to deliver gene-editing DNA code only to cells that are targeted with magnetic field-induced local transduction. Courtesy of the Laboratory of Biomolecular Engineering and Nanomedicine

Kudos to whomever put that diagram together! That’s a lot of well conveyed information.

Now for the details about how this technology might save lives. From a November 13, 2018 news item on Nanowerk,

A new technology that relies on a moth-infecting virus and nanomagnets could be used to edit defective genes that give rise to diseases like sickle cell, muscular dystrophy and cystic fibrosis.

Rice University bioengineer Gang Bao has combined magnetic nanoparticles with a viral container drawn from a particular species of moth to deliver CRISPR/Cas9 payloads that modify genes in a specific tissue or organ with spatial control.

A November 12, 2018 Rice University news release (also on EurekAlert published on November 13, 2018), which originated the news item, provides detail,

Because magnetic fields are simple to manipulate and, unlike light, pass easily through tissue, Bao and his colleagues want to use them to control the expression of viral payloads in target tissues by activating the virus that is otherwise inactivated in blood.

The research appears in Nature Biomedical Engineering. In nature, CRISPR/Cas9 bolsters microbes’ immune systems by recording the DNA of invaders. That gives microbes the ability to recognize and attack returning invaders, but scientists have been racing to adapt CRISPR/Cas9 to repair mutations that cause genetic diseases and to manipulate DNA in laboratory experiments.

CRISPR/Cas9 has the potential to halt hereditary disease – if scientists can get the genome-editing machinery to the right cells inside the body. But roadblocks remain, especially in delivering the gene-editing payloads with high efficiency.

Bao said it will be necessary to edit cells in the body to treat many diseases. “But efficiently delivering genome-editing machinery into target tissue in the body with spatial control remains a major challenge,” Bao said. “Even if you inject the viral vector locally, it can leak to other tissues and organs, and that could be dangerous.”

The delivery vehicle developed by Bao’s group is based on a virus that infects Autographa californica, aka the alfalfa looper, a moth native to North America. The cylindrical baculovirus vector (BV), the payload-carrying part of the virus, is considered large at up to 60 nanometers in diameter and 200-300 nanometers in length. That’s big enough to transport more than 38,000 base pairs of DNA, which is enough to supply multiple gene-editing units to a target cell, Bao said.

He said the inspiration to combine BV and magnetic nanoparticles came from discussions with Rice postdoctoral researcher and co-lead author Haibao Zhu, who learned about the virus during a postdoctoral stint in Singapore but knew nothing about magnetic nanoparticles until he joined the Bao lab. The Rice team had previous experience using iron oxide nanoparticles and an applied magnetic field to open blood vessel walls just enough to let large-molecule drugs pass through.

“We really didn’t know if this would work for gene editing or not, but we thought, ‘worth a shot,'” Bao said.

The researchers use the magnetic nanoparticles to activate BV and deliver gene-editing payloads only where they’re needed. To do this, they take advantage of an immune-system protein called C3 that normally inactivates baculoviruses.

“If we combine BV with magnetic nanoparticles, we can overcome this deactivation by applying the magnetic field,” Bao said. “The beauty is that when we deliver it, gene editing occurs only at the tissue, or the part of the tissue, where we apply the magnetic field.”

Application of the magnetic field allows BV transduction, the payload-delivery process that introduces gene-editing cargo into the target cell. The payload is also DNA, which encodes both a reporter gene and the CRISPR/Cas9 system.

In tests, the BV was loaded with green fluorescent proteins or firefly luciferase. Cells with the protein glowed brightly under a microscope, and experiments showed the magnets were highly effective at targeted delivery of BV cargoes in both cell cultures and lab animals.

Bao noted his and other labs are working on the delivery of CRISPR/Cas9 with adeno-associated viruses (AAV), but he said BV’s capacity for therapeutic cargo is roughly eight times larger. “However, it is necessary to make BV transduction into target cells more efficient,” he said.

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

Spatial control of in vivo CRISPR–Cas9 genome editing via nanomagnets by Haibao Zhu, Linlin Zhang, Sheng Tong, Ciaran M. Lee, Harshavardhan Deshmukh, & Gang Bao. Nature Biomedical Engineering (2018) DOI: https://doi.org/10.1038/s41551-018-0318-7 Published: 12 November 2018

This paper is behind a paywall.

Wearable electronic textiles from the UK, India, and Canada: two different carbon materials

It seems wearable electronic textiles may be getting nearer to the marketplace. I have three research items (two teams working with graphene and one working with carbon nanotubes) that appeared on my various feeds within two days of each other.

UK/China

This research study is the result of a collaboration between UK and Chinese scientists. From a May 15, 2019 news item on phys.org (Note: Links have been removed),


Wearable electronic components incorporated directly into fabrics have been developed by researchers at the University of Cambridge. The devices could be used for flexible circuits, healthcare monitoring, energy conversion, and other applications.

The Cambridge researchers, working in collaboration with colleagues at Jiangnan University in China, have shown how graphene – a two-dimensional form of carbon – and other related materials can be directly incorporated into fabrics to produce charge storage elements such as capacitors, paving the way to textile-based power supplies which are washable, flexible and comfortable to wear.

The research, published in the journal Nanoscale, demonstrates that graphene inks can be used in textiles able to store electrical charge and release it when required. The new textile electronic devices are based on low-cost, sustainable and scalable dyeing of polyester fabric. The inks are produced by standard solution processing techniques.

Building on previous work by the same team, the researchers designed inks which can be directly coated onto a polyester fabric in a simple dyeing process. The versatility of the process allows various types of electronic components to be incorporated into the fabric.

Schematic of the textile-based capacitor integrating GNP/polyesters as electrodes and h-BN/polyesters as dielectrics. Credit: Felice Torrisi

A May 16, 2019 University of Cambridge press release, which originated the news item, probes further,

Most other wearable electronics rely on rigid electronic components mounted on plastic or textiles. These offer limited compatibility with the skin in many circumstances, are damaged when washed and are uncomfortable to wear because they are not breathable.

“Other techniques to incorporate electronic components directly into textiles are expensive to produce and usually require toxic solvents, which makes them unsuitable to be worn,” said Dr Felice Torrisi from the Cambridge Graphene Centre, and the paper’s corresponding author. “Our inks are cheap, safe and environmentally-friendly, and can be combined to create electronic circuits by simply overlaying different fabrics made of two-dimensional materials on the fabric.”

The researchers suspended individual graphene sheets in a low boiling point solvent, which is easily removed after deposition on the fabric, resulting in a thin and uniform conducting network made up of multiple graphene sheets. The subsequent overlay of several graphene and hexagonal boron nitride (h-BN) fabrics creates an active region, which enables charge storage. This sort of ‘battery’ on fabric is bendable and can withstand washing cycles in a normal washing machine.

“Textile dyeing has been around for centuries using simple pigments, but our result demonstrates for the first time that inks based on graphene and related materials can be used to produce textiles that could store and release energy,” said co-author Professor Chaoxia Wang from Jiangnan University in China. “Our process is scalable and there are no fundamental obstacles to the technological development of wearable electronic devices both in terms of their complexity and performance.”

The work done by the Cambridge researchers opens a number of commercial opportunities for ink based on two-dimensional materials, ranging from personal health and well-being technology, to wearable energy and data storage, military garments, wearable computing and fashion.

“Turning textiles into functional energy storage elements can open up an entirely new set of applications, from body-energy harvesting and storage to the Internet of Things,” said Torrisi “In the future our clothes could incorporate these textile-based charge storage elements and power wearable textile devices.”

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

Wearable solid-state capacitors based on two-dimensional material all-textile heterostructures by Siyu Qiang, Tian Carey, Adrees Arbab, Weihua Song, Chaoxia Wang and Felice Torris. Nanoscale, 2019, Advance Article DOI: 10.1039/C9NR00463G First published on 18 Apr 2019

This paper is behind a paywall.

India

Prior to graphene’s reign as the ‘it’ carbon material, carbon nanotubes (CNTs) ruled. It’s been quieter on the CNT front since graphene took over but a May 15, 2019 Nanowerk Spotlight article by Michael Berger highlights some of the latest CNT research coming out of India,


The most important technical challenge is to blend the chemical nature of raw materials with fabrication techniques and processability, all of which are diametrically conflicting for textiles and conventional energy storage devices. A team from Indian Institute of Technology Bombay has come out with a comprehensive approach involving simple and facile steps to fabricate a wearable energy storage device. Several scientific and technological challenges were overcome during this process.

First, to achieve user-comfort and computability with clothing, the scaffold employed was the the same as what a regular fabric is made up of – cellulose fibers. However, cotton yarns are electrical insulators and therefore practically useless for any electronics. Therefore, the yarns are coated with single-wall carbon nanotubes (SWNTs).

SWNTs are hollow, cylindrical allotropes of carbon and combine excellent mechanical strength with electrical conductivity and surface area. Such a coating converts the electrical insulating cotton yarn to a metallic conductor with high specific surface area. At the same time, using carbon-based materials ensures that the final material remains light-weight and does not cause user discomfort that can arise from metallic wires such as copper and gold. This CNT-coated cotton yarn (CNT-wires) forms the electrode for the energy storage device.

Next, the electrolyte is composed of solid-state electrolyte sheets since no liquid-state electrolytes can be used for this purpose. However, solid state electrolytes suffer from poor ionic conductivity – a major disadvantage for energy storage applications. Therefore, a steam-based infiltration approach that enhances the ionic conductivity of the electrolyte is adopted. Such enhancement of humidity significantly increases the energy storage capacity of the device.


The integration of the CNT-wire electrode with the electrolyte sheet was carried out by a simple and elegant approach of interweaving the CNT-wire through the electrolyte (see Figure 1). This resulted in cross-intersections which are actually junctions where the electrical energy can be stored. Each such junction is now an energy storage unit, referred to as sewcap.

The advantage of this process is that several 100s and 1000s of sewcaps can be made in a small area and integrated to increase the total amount of energy stored in the system. This scalability is unique and critical aspect of this work and stems from the approach of interweaving.

Further, this process is completely adaptable with current processes used in textile industries. Hence, a proportionately large energy-storage is achieved by creating sewcap-junctions in various combinations.

All components of the final sewcap device are flexible. However, they need to be protected from environmental effects such as temperature, humidity and sweat while retaining the mechanical flexibility. This is achieved by laminating the entire device between polymer sheets. The process is exactly similar to the one used for protecting documents and ID cards.

The laminated sewcap can be integrated easily on clothing and fabrics while retaining the flexibility and sturdiness. This is demonstrated by the unchanged performance of the device during extreme and harsh mechanical testing such as striking repeatedly with a hammer, complete flexing, bending and rolling and washing in a laundry machine.

In fact, this is the first device that has been proven to be stable under rigorous washing conditions in the presence of hot water, detergents and high torque (spinning action of washing machine). This provides the device with comprehensive mechanical stability.


CNTs have high surface area and electrical conductivity. The CNT-wire combines these properties of CNTs with stability and porosity of cellulose yarns. The junction created by interweaving is essentially comprised of two such CNT-wires that are sandwiching an electrolyte. Application of potential difference leads to polarization of the electrolyte thus enabling energy storage similar to the way in which a conventional capacitor acts.

“We use the advantage of the interweaving process and create several such junctions. So, with each junction being able to store a certain amount of electrical energy, all the junctions synchronized are able to store a large amount of energy. This provides high energy density to the device,” Prof. C. Subramaniam, Department of Chemistry, IIT Bombay and corresponding author of the paper points out.

The device has also been employed for lighting up an LED [light-emitting diode]. This can be potentially scaled to provide electrical energy demanded by the application.

This image accompanies the paper written by Prof. C. Subramaniam and his team,

Courtesy: IACS Applied Materials Interfaces

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

Interwoven Carbon Nanotube Wires for High-Performing, Mechanically Robust, Washable, and Wearable Supercapacitors by Mihir Kumar Jha, Kenji Hata, and Chandramouli Subramaniam. ACS Appl. Mater. Interfaces, Article ASAP DOI: 10.1021/acsami.8b22233 Publication Date (Web): April 29, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.

Canada

A research team from the University of British Columbia (UBC at the Okanagan Campus) joined the pack with a May 16, 2019 news item on ScienceDaily,

Forget the smart watch. Bring on the smart shirt.

Researchers at UBC Okanagan’s School of Engineering have developed a low-cost sensor that can be interlaced into textiles and composite materials. While the research is still new, the sensor may pave the way for smart clothing that can monitor human movement.

A May 16, 2019 UBC news release (also on EurekAlert), which originated the news item, describes the work in more detail,


“Microscopic sensors are changing the way we monitor machines and humans,” says Hoorfar, lead researcher at the Advanced Thermo-Fluidic Lab at UBC’s Okanagan campus. “Combining the shrinking of technology along with improved accuracy, the future is very bright in this area.”

This ‘shrinking technology’ uses a phenomenon called piezo-resistivity—an electromechanical response of a material when it is under strain. These tiny sensors have shown a great promise in detecting human movements and can be used for heart rate monitoring or temperature control, explains Hoorfar.

Her research, conducted in partnership with UBC Okanagan’s Materials and Manufacturing Research Institute, shows the potential of a low-cost, sensitive and stretchable yarn sensor. The sensor can be woven into spandex material and then wrapped into a stretchable silicone sheath. This sheath protects the conductive layer against harsh conditions and allows for the creation of washable wearable sensors.

While the idea of smart clothing—fabrics that can tell the user when to hydrate, or when to rest—may change the athletics industry, UBC Professor Abbas Milani says the sensor has other uses. It can monitor deformations in fibre-reinforced composite fabrics currently used in advanced industries such as automotive, aerospace and marine manufacturing.

The low-cost stretchable composite sensor has also shown a high sensitivity and can detect small deformations such as yarn stretching as well as out-of-plane deformations at inaccessible places within composite laminates, says Milani, director of the UBC Materials and Manufacturing Research Institute.

The testing indicates that further improvements in its accuracy could be achieved by fine-tuning the sensor’s material blend and improving its electrical conductivity and sensitivity This can eventually make it able to capture major flaws like “fibre wrinkling” during the manufacturing of advanced composite structures such as those currently used in airplanes or car bodies.

“Advanced textile composite materials make the most of combining the strengths of different reinforcement materials and patterns with different resin options,” he says. “Integrating sensor technologies like piezo-resistive sensors made of flexible materials compatible with the host textile reinforcement is becoming a real game-changer in the emerging era of smart manufacturing and current automated industry trends.”

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

Graphene‐Coated Spandex Sensors Embedded into Silicone Sheath for Composites Health Monitoring and Wearable Applications by Hossein Montazerian, Armin Rashidi, Arash Dalili, Homayoun Najjaran, Abbas S. Milani, Mina Hoorfar. Small Volume15, Issue17 April 26, 2019 1804991 DOI: https://doi.org/10.1002/smll.201804991 First published: 28 March 2019

This paper is behind a paywall.

Will there be one winner or will they find CNTs better for one type of wearable tech textile while graphene excels for another type of wearable tech textile?