Category Archives: medicine

Hopes for nanocellulose in the fields of medicine and green manufacturing

Initially this seemed like an essay extolling the possibilities for nanocellulose but it is also a research announcement. From a Nov. 7, 2016 news item on Nanowerk,

What if you could take one of the most abundant natural materials on earth and harness its strength to lighten the heaviest of objects, to replace synthetic materials, or use it in scaffolding to grow bone, in a fast-growing area of science in oral health care?

This all might be possible with cellulose nanocrystals, the molecular matter of all plant life. As industrial filler material, they can be blended with plastics and other synthetics. They are as strong as steel, tough as glass, lightweight, and green.

“Plastics are currently reinforced with fillers made of steel, carbon, Kevlar, or glass. There is an increasing demand in manufacturing for sustainable materials that are lightweight and strong to replace these fillers,” said Douglas M. Fox, associate professor of chemistry at American University.
“Cellulose nanocrystals are an environmentally friendly filler. If there comes a time that they’re used widely in manufacturing, cellulose nanocrystals will lessen the weight of materials, which will reduce energy.”

A Nov. 7, 2016 American University news release on EurekAlert, which originated the news item, continues into the research,

Fox has submitted a patent for his work with cellulose nanocrystals, which involves a simple, scalable method to improve their performance. Published results of his method can be found in the chemistry journal ACS Applied Materials and Interfaces. Fox’s method could be used as a biomaterial and for applications in transportation, infrastructure and wind turbines.

The power of cellulose

Cellulose gives stems, leaves and other organic material in the natural world their strength. That strength already has been harnessed for use in many commercial materials. At the nano-level, cellulose fibers can be broken down into tiny crystals, particles smaller than ten millionths of a meter. Deriving cellulose from natural sources such as wood, tunicate (ocean-dwelling sea cucumbers) and certain kinds of bacteria, researchers prepare crystals of different sizes and strengths.

For all of the industry potential, hurdles abound. As nanocellulose disperses within plastic, scientists must find the sweet spot: the right amount of nanoparticle-matrix interaction that yields the strongest, lightest property. Fox overcame four main barriers by altering the surface chemistry of nanocrystals with a simple process of ion exchange. Ion exchange reduces water absorption (cellulose composites lose their strength if they absorb water); increases the temperature at which the nanocrystals decompose (needed to blend with plastics); reduces clumping; and improves re-dispersal after the crystals dry.

Cell growth

Cellulose nanocrystals as a biomaterial is yet another commercial prospect. In dental regenerative medicine, restoring sufficient bone volume is needed to support a patient’s teeth or dental implants. Researchers at the National Institute of Standards and Technology [NIST], through an agreement with the National Institute of Dental and Craniofacial Research of the National Institutes of Health, are looking for an improved clinical approach that would regrow a patient’s bone. When researchers experimented with Fox’s modified nanocrystals, they were able to disperse the nanocrystals in scaffolds for dental regenerative medicine purposes.

“When we cultivated cells on the cellulose nanocrystal-based scaffolds, preliminary results showed remarkable potential of the scaffolds for both their mechanical properties and the biological response. This suggests that scaffolds with appropriate cellulose nanocrystal concentrations are a promising approach for bone regeneration,” said Martin Chiang, team leader for NIST’s Biomaterials for Oral Health Project.

Another collaboration Fox has is with Georgia Institute of Technology and Owens Corning, a company specializing in fiberglass insulation and composites, to research the benefits to replace glass-reinforced plastic used in airplanes, cars and wind turbines. He also is working with Vireo Advisors and NIST to characterize the health and safety of cellulose nanocrystals and nanofibers.

“As we continue to show these nanomaterials are safe, and make it easier to disperse them into a variety of materials, we get closer to utilizing nature’s chemically resistant, strong, and most abundant polymer in everyday products,” Fox said.

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

Simultaneously Tailoring Surface Energies and Thermal Stabilities of Cellulose Nanocrystals Using Ion Exchange: Effects on Polymer Composite Properties for Transportation, Infrastructure, and Renewable Energy Applications by Douglas M. Fox, Rebeca S. Rodriguez, Mackenzie N. Devilbiss, Jeremiah Woodcock, Chelsea S. Davis, Robert Sinko, Sinan Keten, and Jeffrey W. Gilman. ACS Appl. Mater. Interfaces, 2016, 8 (40), pp 27270–27281 DOI: 10.1021/acsami.6b06083 Publication Date (Web): September 14, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

Getting your brain cells to glow in the dark

The extraordinary effort to colonize our brains continues apace with a new sensor from Vanderbilt University. From an Oct. 27, 2016 news item on ScienceDaily,

A new kind of bioluminescent sensor causes individual brain cells to imitate fireflies and glow in the dark.

The probe, which was developed by a team of Vanderbilt scientists, is a genetically modified form of luciferase, the enzyme that a number of other species including fireflies use to produce light. …

The scientists created the technique as a new and improved method for tracking the interactions within large neural networks in the brain.

“For a long time neuroscientists relied on electrical techniques for recording the activity of neurons. These are very good at monitoring individual neurons but are limited to small numbers of neurons. The new wave is to use optical techniques to record the activity of hundreds of neurons at the same time,” said Carl Johnson, Stevenson Professor of Biological Sciences, who headed the effort.

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

Individual neuron glowing with bioluminescent light produced by a new genetically engineered sensor. (Johnson Lab / Vanderbilt University)

An Oct. 27, 2016 Vanderbilt University news release (also on EurekAlert) by David Salisbury, which originated the news item, explains the work in more detail,

“Most of the efforts in optical recording use fluorescence, but this requires a strong external light source which can cause the tissue to heat up and can interfere with some biological processes, particularly those that are light sensitive,” he [Carl Johnson] said.

Based on their research on bioluminescence in “a scummy little organism, the green alga Chlamydomonas, that nobody cares much about” Johnson and his colleagues realized that if they could combine luminescence with optogenetics – a new biological technique that uses light to control cells, particularly neurons, in living tissue – they could create a powerful new tool for studying brain activity.

“There is an inherent conflict between fluorescent techniques and optogenetics. The light required to produce the fluorescence interferes with the light required to control the cells,” said Johnson. “Luminescence, on the other hand, works in the dark!”

Johnson and his collaborators – Associate Professor Donna Webb, Research Assistant Professor Shuqun Shi, post-doctoral student Jie Yang and doctoral student Derrick Cumberbatch in biological sciences and Professor Danny Winder and postdoctoral student Samuel Centanni in molecular physiology and biophysics – genetically modified a type of luciferase obtained from a luminescent species of shrimp so that it would light up when exposed to calcium ions. Then they hijacked a virus that infects neurons and attached it to their sensor molecule so that the sensors are inserted into the cell interior.

The researchers picked calcium ions because they are involved in neuron activation. Although calcium levels are high in the surrounding area, normally they are very low inside the neurons. However, the internal calcium level spikes briefly when a neuron receives an impulse from one of its neighbors.

They tested their new calcium sensor with one of the optogenetic probes (channelrhodopsin) that causes the calcium ion channels in the neuron’s outer membrane to open, flooding the cell with calcium. Using neurons grown in culture they found that the luminescent enzyme reacted visibly to the influx of calcium produced when the probe was stimulated by brief light flashes of visible light.

To determine how well their sensor works with larger numbers of neurons, they inserted it into brain slices from the mouse hippocampus that contain thousands of neurons. In this case they flooded the slices with an increased concentration of potassium ions, which causes the cell’s ion channels to open. Again, they found that the sensor responded to the variations in calcium concentrations by brightening and dimming.

“We’ve shown that the approach works,” Johnson said. “Now we have to determine how sensitive it is. We have some indications that it is sensitive enough to detect the firing of individual neurons, but we have to run more tests to determine if it actually has this capability.”

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

Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing by Jie Yang, Derrick Cumberbatch, Samuel Centanni, Shu-qun Shi, Danny Winder, Donna Webb, & Carl Hirschie Johnson. Nature Communications 7, Article number: 13268 (2016)  doi:10.1038/ncomms13268 Published online: 27 October 2016

This paper is open access.

Nanofiber coating for artificial joints and implants

The researchers have a great image to accompany their research, which fit well with Hallowe’en and the Day of the Dead celebrations taking place around the same time as the research was published.

 A titanium implant (blue) without a nanofiber coating in the femur of a mouse. Bacteria are shown in red and responding immune cells in yellow. Credit: Lloyd Miller/Johns Hopkins Medicine

A titanium implant (blue) without a nanofiber coating in the femur of a mouse. Bacteria are shown in red and responding immune cells in yellow.
Credit: Lloyd Miller/Johns Hopkins Medicine

An Oct. 24, 2016 news item on ScienceDaily announces the research on nanofibers,

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial infections related to total joint replacement surgery.

An Oct. 24, 2016 Johns Hopkins Medicine news release (also on EurekAlert), provides further details (Note: Links have been removed),

A report on the study, published online the week of Oct. 24 [2016] in Proceedings of the National Academy of Sciences, was conducted on the rodents’ knee joints, but, the researchers say, the technology would have “broad applicability” in the use of orthopaedic prostheses, such as hip and knee total joint replacements, as well pacemakers, stents and other implantable medical devices. In contrast to other coatings in development, the researchers report the new material can release multiple antibiotics in a strategically timed way for an optimal effect.

“We can potentially coat any metallic implant that we put into patients, from prosthetic joints, rods, screws and plates to pacemakers, implantable defibrillators and dental hardware,” says co-senior study author Lloyd S. Miller, M.D., Ph.D., an associate professor of dermatology and orthopaedic surgery at the Johns Hopkins University School of Medicine.

Surgeons and biomedical engineers have for years looked for better ways —including antibiotic coatings — to reduce the risk of infections that are a known complication of implanting artificial hip, knee and shoulder joints.

Every year in the U.S., an estimated 1 to 2 percent of the more than 1 million hip and knee replacement surgeries are followed by infections linked to the formation of biofilms — layers of bacteria that adhere to a surface, forming a dense, impenetrable matrix of proteins, sugars and DNA. Immediately after surgery, an acute infection causes swelling and redness that can often be treated with intravenous antibiotics. But in some people, low-grade chronic infections can last for months, causing bone loss that leads to implant loosening and ultimately failure of the new prosthesis. These infections are very difficult to treat and, in many cases of chronic infection, prostheses must be removed and patients placed on long courses of antibiotics before a new prosthesis can be implanted. The cost per patient often exceeds $100,000 to treat a biofilm-associated prosthesis infection, Miller says.

Major downsides to existing options for local antibiotic delivery, such as antibiotic-loaded cement, beads, spacers or powder, during the implantation of medical devices are that they can typically only deliver one antibiotic at a time and the release rate is not well-controlled. To develop a better approach that addresses those problems, Miller teamed up with Hai-Quan Mao, Ph.D., a professor of materials science and engineering at the Johns Hopkins University Whiting School of Engineering, and a member of the Institute for NanoBioTechnology, Whitaker Biomedical Engineering Institute and Translational Tissue Engineering Center.

Over three years, the team focused on designing a thin, biodegradable plastic coating that could release multiple antibiotics at desired rates. This coating is composed of a nanofiber mesh embedded in a thin film; both components are made of polymers used for degradable sutures.

To test the technology’s ability to prevent infection, the researchers loaded the nanofiber coating with the antibiotic rifampin in combination with one of three other antibiotics: vancomycin, daptomycin or linezolid. “Rifampin has excellent anti-biofilm activity but cannot be used alone because bacteria would rapidly develop resistance,” says Miller. The coatings released vancomycin, daptomycin or linezolid for seven to 14 days and rifampin over three to five days. “We were able to deploy two antibiotics against potential infection while ensuring rifampin was never present as a single agent,” Miller says.

The team then used each combination to coat titanium Kirschner wires — a type of pin used in orthopaedic surgery to fix bone in place after wrist fractures — inserted them into the knee joints of anesthetized mice and introduced a strain of Staphylococcus aureus, a bacterium that commonly causes biofilm-associated infections in orthopaedic surgeries. The bacteria were engineered to give off light, allowing the researchers to noninvasively track infection over time.

Miller says that after 14 days of infection in mice that received an antibiotic-free coating on the pins, all of the mice had abundant bacteria in the infected tissue around the knee joint, and 80 percent had bacteria on the surface of the implant. In contrast, after the same time period in mice that received pins with either linezolid-rifampin or daptomycin-rifampin coating, none of the mice had detectable bacteria either on the implants or in the surrounding tissue.

“We were able to completely eradicate infection with this coating,” says Miller. “Most other approaches only decrease the number of bacteria but don’t generally or reliably prevent infections.”

After the two-week test, each of the rodents’ joints and adjacent bones were removed for further study. Miller and Mao found that not only had infection been prevented, but the bone loss often seen near infected joints — which creates the prosthetic loosening in patients — had also been completely avoided in animals that received pins with the antibiotic-loaded coating.

Miller emphasized that further research is needed to test the efficacy and safety of the coating in humans, and in sorting out which patients would best benefit from the coating — people with a previous prosthesis joint infection receiving a new replacement joint, for example.

The polymers they used to generate the nanofiber coating have already been used in many approved devices by the U.S. Food and Drug Administration, such as degradable sutures, bone plates and drug delivery systems.

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

Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo by Alyssa G. Ashbaugh, Xuesong Jiang, Jesse Zheng, Andrew S. Tsai, Woo-Shin Kim, John M. Thompson, Robert J. Miller, Jonathan H. Shahbazian, Yu Wang, Carly A. Dillen, Alvaro A. Ordonez, Yong S. Chang, Sanjay K. Jain, Lynne C. Jones, Robert S. Sterling, Hai-Quan Mao, and Lloyd S. Miller. PNAS [Proceedings of the National Academy of Sciences] 2016 doi: 10.1073/pnas.1613722113 Published ahead of print October 24, 2016

This paper is behind a paywall.

Nano-decoy for human influenza A virus

While the implications for this research are exciting, keep in mind that so far they’ve been testing immune-compromised mice. An Oct. 24, 2016 news item on Nanowerk announces the research,

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic acid lures the influenza A virus to its doom. When misted into the lungs, the nanoparticle traps influenza A, holding it until the virus self-destructs.

An Oct. 24, 2015 Rensselaer Polytechnic Institute press release by Mary L. Martialay, which originated the news item, describes the research (Note: Links have been removed),

In a study on immune-compromised mice, the treatment reduced influenza A mortality from 100 percent to 25 percent over 14 days. The novel approach, which is radically different from existing influenza A vaccines, and treatments based on neuraminidase inhibitors, could be extended to a host of viruses that use a similar approach to infecting humans, such as Zika, HIV, and malaria. …

“Instead of blocking the virus, we mimicked its target – it’s a completely novel approach,” said Robert Linhardt, a glycoprotein expert and Rensselaer Polytechnic Institute professor who led the research. “It is effective with influenza and we have reason to believe it will function with many other viruses. This could be a therapeutic in cases where vaccine is not an option, such as exposure to an unanticipated strain, or with immune-compromised patients.”

The project is a collaboration between researchers within the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer and several institutions in South Korea including Kyungpook National University. Lead author Seok-Joon Kwon, a CBIS research scientist, coordinated the project across borders, enabling the South Korean institutions to test a drug designed and characterized at Rensselaer. …

To access the interior of a cell and replicate itself, influenza A must first bind to the cell surface, and then cut itself free. It binds with the protein hemagglutinin, and severs that tie with the enzyme neuraminidase. Influenza A produces numerous variations each of hemagglutinin and neuraminidase, all of which are antigens within the pathogen that provoke an immune system response. Strains of influenza A are characterized according to the variation of hemagglutinin and neuraminidase they carry, thus the origin of the familiar H1N1 or H3N2 designations.

Medications to counter the virus do exist, but all are vulnerable to the continual antigenic evolution of the virus. A yearly vaccine is effective only if it matches the strain of virus that infects the body. And the virus has shown an ability to develop resistance to a class of therapeutics based on neuraminidase inhibitors, which bind to and block neuraminidase.

The new solution targets an aspect of infection that does not change: all hemagglutinin varieties of influenza A must bind to human sialic acid. To trap the virus, the team designed a dendrimer, a spherical nanoparticle with treelike branches emanating from its core. On the outermost branches, they attached molecules, or “ligands,” of sialic acid.

The research found that the size of the dendrimer and the spacing between the ligands is integral to the function of the nanoparticle. Hemagglutinin occurs in clusters of three, or “trimers,” on the surface of the virus, and researchers found that a spacing of 3 nanometers between ligands resulted in the strongest binding to the trimers. Once bound to the densely packed dendrimer, viral neuraminidase is unable to sever the link. The coat of the virus contains millions of trimers, but the research revealed that only a few links provokes the virus to discharge its genetic cargo and ultimately self-destruct.

A different approach, using a less structured nanoparticle, had been previously tested in unrelated research, but the nanoparticle selected proved both toxic, and could be inactivated by neuraminidase. The new approach is far more promising.

“The major accomplishment was in designing an architecture that is optimized to bind so tightly to the hemagglutinin, the neuraminidase can’t squeeze in and free the virus,” said Linhardt. “It’s trapped.”

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

Nanostructured glycan architecture is important in the inhibition of influenza A virus infection by Seok-Joon Kwon, Dong Hee Na, Jong Hwan Kwak, Marc Douaisi, Fuming Zhang, Eun Ji Park, Jong-Hwan Park, Hana Youn, Chang-Seon Song, Ravi S. Kane, Jonathan S. Dordick, Kyung Bok Lee, & Robert J. Linhardt. Nature Nanotechnology (2016)  doi:10.1038/nnano.2016.181 Published online 24 October 2016

This paper is behind a paywall.

Growing and sharpening gold

An Oct. 19, 2016 news item on phys.org compares nanogold to a snowflake,

Grown like a snowflake and sharpened with a sewing machine, a novel device by Kansas State University researchers may benefit biomedical professionals and the patients they serve during electrode and organ transplant procedures.

The device uses gold nanowires and was developed by Bret Flanders, associate professor of physics, and Govind Paneru, former graduate research assistant in physics, to manipulate and sense characteristics of individual cells in medical procedures. The gold nanowires are 1,000 times smaller than a human hair.

An Oct. 19, 2016 Kansas State University news release (also on EurekAlert) by Tiffany Roney, which originated the news item, expands on the theme,

“Conventional surgical tools, including electrodes that are implanted in people’s tissue, are unfavorably large on the cellular level,” Flanders said. “Working at the individual cellular level is of increasing importance in areas such as neurosurgery. Potentially, this sleek device, made from gold nanowires, could get in close and do the job.”

Flanders said the size of the nanowires is what makes their device so unique.

Each wire is less than 100 nanometers in diameter. Cells in skin and hair are about 10-20 micrometers in diameter, while red blood cells measure about 7 micrometers. Because the wire is so small, it can pierce a biological cell to stimulate the cell membrane and investigate its interior.

The nanowires are electrochemically grown, meaning they do not grow by a lengthening or enlarging an existing wire, but rather by accumulating particles from solution into a new wire.

In heavily zoomed video footage the nanowire appears to grow out of the micrometer-thick electrode. Actually, the nanowire forms similarly to how a snowflake is assembled in the sky when water vapor molecules in the air condense onto the surface of pollen or dust and grow non-uniformly until they become a recognizable snowflake.

“We start with a sharp microelectrode on a microscope stage,” Flanders said. “Similar to snowflake formation, the gold atoms condense onto its sharp tip. Like the water condensing onto the snowflake seed, the golden solution condenses onto the gold ‘seed,’ or the microelectrode.”

The researchers developed sharp electrodes with an unconventional tool not found in many laboratories: a sewing machine.

“It’s like putting the wire in a pencil sharpener, where you turn the crank to sharpen it, except we don’t do it mechanically with a pencil sharpener — we do it with a common salt solution and a sewing machine,” Flanders said. “This turned out to be the approach that worked the best, and the sewing machine cost only $10 at the Salvation Army.”

The sewing machine oscillates the microelectrode up and down in a beaker of potassium chloride solution. Application of a voltage dissolves the tip of the microelectrode.

“The process sharpens the electrode because the tip is in the solution longer than any other point,” Flanders said. “If we did not oscillate the wire, the whole wire would dissolve. Instead, dipping the tip in and out causes the tip to dissolve the most, thereby sharpening it.”

The sharpened electrode allows the nanowire to grow. The researchers then dismount the nanowire from the electrode and ship it to collaborators across the country, including a nanofabrication company that may incorporate the invention into a pre-existing device to provide it with greater power.

There are two published pieces associated with the research but they are older. Here’s a link to and a citation for each,

Single-step growth and low resistance interconnecting of gold nanowires by Birol Ozturk, Bret N Flanders, Daniel R Grischkowsky, and Tetsuya D Mishima. Nanotechnology, Volume 18, Number 17 doi:10.1088/0957-4484/18/17/175707 Published 2 April 2007
Directed growth of single-crystal indium wires by Ishan Talukdar, Birol Ozturk, Bret N. Flanders, and Tetsuya D. Mishima. Appl. Phys. Lett. 88, 221907 (2006); http://dx.doi.org/10.1063/1.2208431 Published online 31 May 2006

Both papers are behind paywalls.

Stretchy optical materials for implants that could pulse light

An Oct. 17, 2016 Massachusetts Institute of Technology (MIT) news release (also on EurekAlert) by Emily Chu describes research that could lead to long-lasting implants offering preventive health strategies,

Researchers from MIT and Harvard Medical School have developed a biocompatible and highly stretchable optical fiber made from hydrogel — an elastic, rubbery material composed mostly of water. The fiber, which is as bendable as a rope of licorice, may one day be implanted in the body to deliver therapeutic pulses of light or light up at the first sign of disease. [emphasis mine]

The researchers say the fiber may serve as a long-lasting implant that would bend and twist with the body without breaking down. The team has published its results online in the journal Advanced Materials.

Using light to activate cells, and particularly neurons in the brain, is a highly active field known as optogenetics, in which researchers deliver short pulses of light to targeted tissues using needle-like fibers, through which they shine light from an LED source.

“But the brain is like a bowl of Jell-O, whereas these fibers are like glass — very rigid, which can possibly damage brain tissues,” says Xuanhe Zhao, the Robert N. Noyce Career Development Associate Professor in MIT’s Department of Mechanical Engineering. “If these fibers could match the flexibility and softness of the brain, they could provide long-term more effective stimulation and therapy.”

Getting to the core of it

Zhao’s group at MIT, including graduate students Xinyue Liu and Hyunwoo Yuk, specializes in tuning the mechanical properties of hydrogels. The researchers have devised multiple recipes for making tough yet pliable hydrogels out of various biopolymers. The team has also come up with ways to bond hydrogels with various surfaces such as metallic sensors and LEDs, to create stretchable electronics.

The researchers only thought to explore hydrogel’s use in optical fibers after conversations with the bio-optics group at Harvard Medical School, led by Associate Professor Seok-Hyun (Andy) Yun. Yun’s group had previously fabricated an optical fiber from hydrogel material that successfully transmitted light through the fiber. However, the material broke apart when bent or slightly stretched. Zhao’s hydrogels, in contrast, could stretch and bend like taffy. The two groups joined efforts and looked for ways to incorporate Zhao’s hydrogel into Yun’s optical fiber design.

Yun’s design consists of a core material encased in an outer cladding. To transmit the maximum amount of light through the core of the fiber, the core and the cladding should be made of materials with very different refractive indices, or degrees to which they can bend light.

“If these two things are too similar, whatever light source flows through the fiber will just fade away,” Yuk explains. “In optical fibers, people want to have a much higher refractive index in the core, versus cladding, so that when light goes through the core, it bounces off the interface of the cladding and stays within the core.”

Happily, they found that Zhao’s hydrogel material was highly transparent and possessed a refractive index that was ideal as a core material. But when they tried to coat the hydrogel with a cladding polymer solution, the two materials tended to peel apart when the fiber was stretched or bent.

To bond the two materials together, the researchers added conjugation chemicals to the cladding solution, which, when coated over the hydrogel core, generated chemical links between the outer surfaces of both materials.

“It clicks together the carboxyl groups in the cladding, and the amine groups in the core material, like molecular-level glue,” Yuk says.

Sensing strain

The researchers tested the optical fibers’ ability to propagate light by shining a laser through fibers of various lengths. Each fiber transmitted light without significant attenuation, or fading. They also found that fibers could be stretched over seven times their original length without breaking.

Now that they had developed a highly flexible and robust optical fiber, made from a hydrogel material that was also biocompatible, the researchers began to play with the fiber’s optical properties, to see if they could design a fiber that could sense when and where it was being stretched.

They first loaded a fiber with red, green, and blue organic dyes, placed at specific spots along the fiber’s length. Next, they shone a laser through the fiber and stretched, for instance, the red region. They measured the spectrum of light that made it all the way through the fiber, and noted the intensity of the red light. They reasoned that this intensity relates directly to the amount of light absorbed by the red dye, as a result of that region being stretched.

In other words, by measuring the amount of light at the far end of the fiber, the researchers can quantitatively determine where and by how much a fiber was stretched.

“When you stretch a certain portion of the fiber, the dimensions of that part of the fiber changes, along with the amount of light that region absorbs and scatters, so in this way, the fiber can serve as a sensor of strain,” Liu explains.

“This is like a multistrain sensor through a single fiber,” Yuk adds. “So it can be an implantable or wearable strain gauge.”

The researchers imagine that such stretchable, strain-sensing optical fibers could be implanted or fitted along the length of a patient’s arm or leg, to monitor for signs of improving mobility.

Zhao envisions the fibers may also serve as sensors, lighting up in response to signs of disease.

“We may be able to use optical fibers for long-term diagnostics, to optically monitor tumors or inflammation,” he says. “The applications can be impactful.”

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

Highly Stretchable, Strain Sensing Hydrogel Optical Fibers by Jingjing Guo, Xinyue Liu, Nan Jiang, Ali K. Yetisen, Hyunwoo Yuk, Changxi Yang, Ali Khademhosseini, Xuanhe Zhao, and Seok-Hyun Yun. Advanced Materials DOI: 10.1002/adma.201603160 Version of Record online: 7 OCT 2016

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Treating bandages with enzymes and polyethylene glycol or cellulase* could make antibacterial nanoparticles better adhere

It’s been a while since I’ve featured research from Iran. This work is focused on bandages, burns, and nanoparticles according to an Oct. 18, 2016 news item on Nanowerk (Note: A link has been removed),

Pre-treating the fabric surface of the bandages used to treat burns with enzymes and polyethylene glycol or cellulase may promote the adhesion of antibacterial nanoparticles and improve their bacteria-repelling ability. These are the findings of a group of scientists from the Islamic Azad University, Iran, published in The Journal of The Textile Institute (“NiO-/cotton- modified nanocomposite as a medication model for bacterial-related burn infection”).

An Oct. 18, 2016 Taylor & Francis (Publishing) Group press release (received via email), which originated the news item, expands on the theme,

Injuries caused by burns are a global health problem, with the World Health Organisation citing 195,000 deaths per year worldwide as a result of burns from fires alone. Burn injuries are particularly susceptible to infections, hospital-acquired or otherwise, with the bacteria Pseudomonas aeruginosa accounting for over half of all severe burn infections.

Noble metal (particularly silver) antimicrobials have long been identified as having potential for combating bacterial infection; however, there are concerns about dressings adhering to wounds and toxic effects on skin cells. Currently, scientists are researching nanoparticles which can be used to introduce these antimicrobial properties into the textiles used in dressings.

The authors of this paper have studied 150 cases to identify the most common infections in burns. In the paper, they also identified a method for giving cotton bandages antibacterial properties by coating the fabric surface with a Nickel oxide (NiO)/organic polymer/enzyme matrix in order to promote their bacteria-resistant qualities and suitability for use on burn victims.

Pseudomonas and Staphylococci infections emerged as the two most common pathogens in the Iran Burn Centre, where the study took place, and the authors evaluated their design of the bandage against these as well as fifteen other strains of bacteria. They conclude by proposing further studies into the combination of bactericidal polymers with bacteria-killing metal-oxide nanoparticles in cotton fabrics. Whilst their current design does not meet the criteria for a susceptibility test, they are hopeful that further studies will reveal the clinical relevance of their design.

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

NiO-/cotton- modified nanocomposite as a medication model for bacterial-related burn infections by Azadeh Basiri, Nasrin Talebian & Monir Doudi. The Journal of The Textile Institute http://dx.doi.org/10.1080/00405000.2016.1222863
Pages 1-9 Published online: 12 Sep 2016

This paper is behind a paywall.

*’Cellulase’ changed to ‘Cellulose’ Nov. 15, 2016 at 1832 PT and changed back again on Nov. 16, 2016. Sorry for the confusion but by the time I published this piece I’d forgotten checking to confirm the existence of cellulase.

Science innovation (nanomedicine) can be tough

Robert Langer is a well known researcher in the field of nanomedicine. Weirdly not included in a listing of prominent nanoscientists in a series by Slate.com writers (my Oct. 7, 2016 posting), it seems the English are making up for this oversight. Amy Fleming in an Oct. 17, 2016 article for the Guardian tells Langer’s story in the context of his recent award of the £1m Queen Elizabeth prize for engineering (Note: Links have been removed),

Robert Langer seems incredibly well adjusted for a man with transatlantic jetlag. And, for that matter, for someone who struggled for years to get his pioneering work in drug delivery accepted by the scientific establishment. As a young professor, his first nine research grant applications were turned down. Once, at a formal dinner in the early 80s, a senior colleague blew smoke in his eyes and told him to find another job.

And yet here he is, a good-natured nanotechnology trailblazer, swooping into the UK for duties associated with having won the £1m Queen Elizabeth prize for engineering. His work has improved the lives of 2 billion people and counting. He has collected awards from two US presidents, as well as the Queen. He has more than 1,000 patents on the go, and 30 companies have spun out from his vast lab at Massachusetts Institute of Technology (the largest biomedical lab in the world). At 68, he is still the future.

… the huge range of his research interests. There’s contraceptive microchip implants; a gel to repair damaged vocal cords; spinal cord repair tissue; an invisible “second skin” for conditions such as eczema (with the cosmetic side effect of rendering skin smooth and elastic); cutting-edge anti-frizz haircare; and what Langer calls “super-long-acting capsules or pills, that would last a week, a month, or even a year”. …

Fleming describes some of Langer’s innovations in more detail (Note: Links have been removed),

Commonly, when pharmaceuticals enter the body, they are coated in synthetic substances called polymers. These allow effective amounts of the drug to reach the body, slowly enough so as not to cause toxicity. Until Langer came along, this controlled method only worked for simpler, small-molecule drugs. Sophisticated large-molecule drugs, that can target diseases such as cancer, diabetes and mental illness, were too big to pass through polymers. “People wouldn’t think you could walk through a wall either,” he says. “But we built all these tortuous channels in what was the equivalent of the wall so somebody could get through, but they get through very slowly, like driving through London in rush hour.”

Langer also designed biologically tolerable polymer pellets – nanopellets, he calls them – that enable drugs to be implanted directly into cancer tumours. This enabled Langer and the cancer researcher Judah Folkman to isolate the first vascular inhibitors, which stop new blood vessels feeding tumours. “We thought it could be a new way of treating cancer,” Langer says, “and it’s become that. Drugs such as Avastin [bevacizumab] and Eylea [aflibercept] are based, in part, on our early research.” He also created new polymers that could dissolve like a bar of soap and release drugs in a very controlled way over months to years. And he and neurosurgeon Henry Brem developed implants (called gliadel wafers) that could be implanted in the brain to treat brain cancer. Trials in 1996 saw a 63% survival rate against just 19% in the control group.

If you have the time, it’s well worth reading Fleming’s article in its entirety.

Nanotechnology-enabled acupuncture needles

An Oct. 17, 2016 news item on phys.org makes an announcement about nanotechnology-enabled acupuncture needles (Note: The writing style is a little unusual for this kind of announcement),

A Daegu Gyeongbuk Institute of Science and Technology [Korea] research team led by Professor Su-Il In, who developed acupuncture needles combined with nanotechnology, was recognized as the world’s first application of this technology. This development is expected to open new directions in the oriental medicine research field.

Professor Su-Il In’s research team from the Department of Energy Systems Engineering succeeded in developing porous acupuncture needles (hereafter PANs) that offer enhanced therapeutic properties by applying nanotechnology on the acupuncture needles for the first time in the world.

The findings of this experiment, which was conducted in collaboration with DGIST’s research team and the Addiction Control Research Center at Daegu Haany University, have attracted the attention of the relevant academic field in light of the fact that the experiment combined nanotechnology with acupuncture needles.

An Oct. 17, 2016 DGIST press release on EurekAlert, which originated the news item, provides more technical detail,

Professor In’s research team developed PANs with fine pores ranging in sizes from nanometers (nm= one billionth of a meter) to micrometers (? = one millionth of a meter) on the surface of the needles using a nano-electrochemical method.

PANs are formed by anodization, and are characterized by a widened surface of the needles through the following process: anion (F-) contained in the electrolyte bored into the surface of the metal needles (positive) and created fine and uniform pores.

PANs are expected to be as effective as conventional large and long needles by minimizing the sense of pain during acupuncture treatment while expanding the surface area of the needle 20 times greater than conventional acupuncture ones.

Through electrophysiological experiments with rats, In’s research team proved that PANs excel in transferring signals from a spinal dorsal horn by the in vivo stimulation of Shenmen (HT7) points, and in particular, demonstrated that the efficacy of PANs is superior to conventional acupuncture needles in treating alcohol and cocaine addiction in animal experiments.

Applications for international patents for the fabrication technology of PANs developed by DGIST have already been submitted in countries such as the US, China, and Europe. In addition, in the domestic oriental medicine field, the fact that the efficacy of acupuncture needles has been improved through their structural transformation by applying nanotechnology has been recognized and evaluated as the first such instance in the thousand-year history of eastern medicine.

Professor Su-Il In from DGIST’s Department of Energy Systems Engineering said, “The development of nanotechnology has taken science and technology to the next level in various fields such as solar cells, quantum computers, display development, and the like. Based on this experiment’s achievement of combining nanotechnology and oriental medicine, I will continue to conduct research in order to be at the forefront of the scientific population of oriental medicine.”

Director Jae-ha Yang from Daegu Haany University said, “In western medicine, nanotechnology is widely used from diagnosis to treatment; but in eastern medicine, particularly in acupuncture therapy, it is rare to utilize nano science. The findings of this study are expected to open new directions in the field of eastern medicine where nano science is rarely explored and utilized.”

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

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties by Su-ll In, Young S. Gwak, Hye Rim Kim, Abdul Razzaq, Kyeong-Seok Lee, Hee Young Kim, SuChan Chang, Bong Hyo Lee, Craig A. Grimes, & Chae Ha Yang. Scientific Reports 6, Article number: 34061 (2016) doi:10.1038/srep34061 Published online: 07 October 2016

This paper is open access.

A guide to producing transparent electronics

A blue light shines through a clear, implantable medical sensor onto a brain model. See-through sensors, which have been developed by a team of UW–Madison engineers, should help neural researchers better view brain activity. Credit: Justin Williams research group

A blue light shines through a clear, implantable medical sensor onto a brain model. See-through sensors, which have been developed by a team of UW–Madison engineers, should help neural researchers better view brain activity. Credit: Justin Williams research group

Read this Oct. 13, 2016 news item on ScienceDaily if you want to find out how to make your own transparent electronics,

When University of Wisconsin-Madison engineers announced in the journal Nature Communications that they had developed transparent sensors for use in imaging the brain, researchers around the world took notice.

Then the requests came flooding in. “So many research groups started asking us for these devices that we couldn’t keep up,” says Zhenqiang (Jack) Ma, the Lynn H. Matthias Professor and Vilas Distinguished Achievement Professor in electrical and computer engineering at UW-Madison.

As a result, in a paper published in the journal Nature Protocols, the researchers have described in great detail how to fabricate and use transparent graphene neural electrode arrays in applications in electrophysiology, fluorescent microscopy, optical coherence tomography, and optogenetics. “We described how to do these things so we can start working on the next generation,” says Ma.

Although he and collaborator Justin Williams, the Vilas Distinguished Achievement Professor in biomedical engineering and neurological surgery at UW-Madison, patented the technology through the Wisconsin Alumni Research Foundation, they saw its potential for advancements in research. “That little step has already resulted in an explosion of research in this field,” says Williams. “We didn’t want to keep this technology in our lab. We wanted to share it and expand the boundaries of its applications.”

An Oct. 13, 2016 University of Wisconsin-Madison news release, which originated the news item, provides more detail about the paper and the researchers,

‘This paper is a gateway for other groups to explore the huge potential from here,’ says Ma. ‘Our technology demonstrates one of the key in vivo applications of graphene. We expect more revolutionary research will follow in this interdisciplinary field.’

Ma’s group is a world leader in developing revolutionary flexible electronic devices. The see-through, implantable micro-electrode arrays were light years beyond anything ever created.

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

Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics by Dong-Wook Park, Sarah K Brodnick, Jared P Ness, Farid Atry, Lisa Krugner-Higby, Amelia Sandberg, Solomon Mikael, Thomas J Richner, Joseph Novello, Hyungsoo Kim, Dong-Hyun Baek, Jihye Bong, Seth T Frye, Sanitta Thongpang, Kyle I Swanson, Wendell Lake, Ramin Pashaie, Justin C Williams, & Zhenqiang Ma. Nature Protocols 11, 2201–2222 (2016) doi:10.1038/nprot.2016.127 Published online 13 October 2016

Of course this paper is open access. The team’s previous paper published in 2014 was featured here in an Oct. 23, 2014 posting.