Tag Archives: infection

German scientists battle tough mucus

A December 15, 2017 news item on ScienceDaily highlights cystic fibrosis research being done in Germany,

Around one in 3,300 children in Germany is born with Mucoviscidosis [cystic fibrosis; CF]. A characteristic of this illness is that one channel albumen on the cell surface is disturbed by mutations. Thus, the amount of water of different secretions in the body is reduced which creates a tough mucus. As a consequence, inner organs malfunction. Moreover, the mucus blocks the airways. Thus, the self regulatory function of the lung is disturbed, the mucus is colonized by bacteria and chronic infections follow. The lung is so significantly damaged that patients often die or need to have a lung transplant. The average life expectancy of a patient today is around 40 years. This is due to medical progress. Permanent treatment with inhaled antibiotics play a considerable part in this. The treatment can’t avoid the colonization by bacteria completely but it can keep it in check for a longer period of time. However, the bacteria defend themselves with a development of resistance and with the growth of so-called biofilms underneath the layer of mucus, which mostly block off the bacteria in the lower rows like a protective shield.

A complex way to the Pathogens

Scientists of the Friedrich Schiller University Jena, Germany succeeded in developing a much more efficient method to treat the airway infections which are often lethal. Crucial are nanoparticles that transport the antibiotics more efficiently to their destination….

A December 15, 2017 Friedrich Schiller University Jena press release (also on EurekAlert), which originated the news item, expands on the theme,

“Typically, the drugs are applied by inhalation in the body. Then they make a complicated way through the body to the pathogens and many of them don’t make it to their destination,” states Prof. Dr Dagmar Fischer of the chair for Pharmaceutical Technology at the University of Jena, who supervised the project together with her colleague Prof. Dr Mathias Pletz, a pulmonologist and infectious diseases physician, from the Center for Infectious Diseases and Infection Control at the Jena University Hospital. The project was supported by the Deutsche Forschungsgemeinschaft. First of all, the active particles need to have a certain size to be able to reach the deeper airways and not to bounce off somewhere else before. Ultimately, they have to penetrate the thick layer of mucus on the airways as well as the lower layers of the bacteria biofilm.

Nanoparticles travel more efficiently

To overcome the strong defense, the researchers encapsulated the active agents, like the antibiotic Tobramycin, in a polyester polymer. Thus, they created a nanoparticle which they then tested in the laboratory where they beforehand had simulated the present lung situation, in a static as well as in a dynamic state, i. e. with simulated flow movements. Therefore Pletz’s research group had developed new test systems, which are able to mimick the situation of the chronically infected CF-lung. The scientists discovered that their nanoparticle travels more easily through the sponge-like net of the mucus layer and is finally able to kill off the pathogens without any problems. Moreover, an additionally applied coating of polyethylenglycol makes it nearly invisible for the immune system. “All materials of a nanocarrier are biocompatible, biodegradable, nontoxic and therefore not dangerous for humans,” the researcher informs.

However, the Jena scientists don’t know yet exactly why their nanoparticle fights the bacteria so much more efficiently. But they want to finally get clarification in the year ahead. “We have two assumptions: Either the much more efficient transport method advances significantly larger amounts of active ingredients to the center of infection, or the nanoparticle circumvents a defense mechanism, which the bacterium has developed against the antibiotic,” the Jena Pharmacist Fischer explains. “This would mean, that we succeeded in giving back its impact to an antibiotic, which had already lost it through a development of resistance of the bacteria.”

“More specifically, we assume that bacteria from the lower layers of the biofilm transform into dormant persisters and hardly absorb any substances from outside. In this stadium, they are tolerant to most antibiotics, which only kill off self-dividing bacteria. The nanoparticles transport the antibiotics more or less against their will to the inner part of the cell, where they can unfold their impact,” Mathias Pletz adds.

Additionally, the Jena research team had to prepare the nanoparticles for the inhalation. Because at 200 nanometers the particle is too small to get into the deeper airways. “The breathing system filters out particles that are too big as well as those which are too small,” Dagmar Fischer explains. “So, we are left with a preferred window of between one and five micrometers.” The Jena researchers also have promising ideas for resolving this problem.

Coating of Nanoparticles enhances the impact of Antibiotics against Biofilms

The scientists from Jena are at this point already convinced to have found a very promising method to fight respiratory infections of patients with mucoviscidosis. Thus they may be able to contribute to a higher life expectancy of those affected. “We were able to show that the nanoparticle coating improves the impact of the antibiotics against biofilm by a factor of 1,000,” the pulmonologist and infectious diseases physician is happy to say.

It’s exciting news and I wish the researchers great success. Perhaps, one day, they will publish a paper about their work.

Ceria-zirconia nanoparticles for sepsis treatment

South Korean researchers are looking at a new way of dealing with infections (sepsis) according to a July 6, 2017 news item on phys.org,

During sepsis, cells are swamped with reactive oxygen species generated in an aberrant response of the immune system to a local infection. If this fatal inflammatory path could be interfered, new treatment schemes could be developed. Now, Korean scientists report in the journal Angewandte Chemie that zirconia-doped ceria nanoparticles act as effective scavengers of these oxygen radicals, promoting a greatly enhanced surviving rate in sepsis model organisms.

A July 6, 2017 Wiley (Publishers) press release, which originated the news item, provides more detail,

Sepsis proceeds as a vicious cycle of inflammatory reactions of the immune system to a local infection. Fatal consequences can be falling blood pressure and the collapse of organ function. As resistance against antibiotics is growing, scientists turn to the inflammatory pathway as an alternative target for new treatment strategies. Taeghwan Heyon from Seoul National University, Seung-Hoon Lee at Seoul National University Hospital, South Korea, and collaborators explore ceria nanoparticles for their ability to scavenge reactive oxygen species, which play a key role in the inflammatory process. By quickly converting between two oxidation states, the cerium ion can quench typical oxygen radical species like the superoxide anion, the hydroxyl radical anion, or even hydrogen peroxide. But in the living cell, this can only happen if two conditions are met.

The first condition is the size and nature of the particles. Small, two-nanometer-sized particles were coated by a hydrophilic shell of poly(ethylene glycol)-connected phospholipids to make them soluble so that they can enter the cell and remain there. Second, the cerium ion responsible for the quenching (Ce3+) should be accessible on the surface of the nanoparticles, and it must be regenerated after the reactions. Here, the scientists found out that a certain amount of zirconium ions in the structure helped, because “the Zr4+ ions control the Ce3+-to-Ce4+ ratio as well as the rate of conversion between the two oxidation states,” they argued.

The prepared nanoparticles were then tested for their ability to detoxify reactive oxygen species, not only in the test tube, but also in live animal models. The results were clear, as the authors stated: “A single dose of ceria-zirconia nanoparticles successfully attenuated the vicious cycle of inflammatory responses in two sepsis models.” The nanoparticles accumulated in organs where severe immune responses occurred, and they were successful in the eradication of reactive oxygen species, as evidenced with fluorescence microscopy and several other techniques. And importantly, the treated mice and rats had a far higher survival rate.

This work demonstrates that other approaches in sepsis treatment than killing bacteria with antibiotics are possible. Targeting the inflammatory signal pathways in macrophages is a very promising option, and the authors have shown that effective scavenging of reactive oxygen species and stopping inflammation is possible with a suitably designed chemical system like this cerium ion redox system provided by nanoparticles.

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

Ceria–Zirconia Nanoparticles as an Enhanced Multi-Antioxidant for Sepsis Treatment by Min Soh, Dr. Dong-Wan Kang, Dr. Han-Gil Jeong, Dr. Dokyoon Kim, Dr. Do Yeon Kim, Dr. Wookjin Yang, Changyeong Song, Seungmin Baik, In-Young Choi, Seul-Ki Ki, Hyek Jin Kwon, Dr. Taeho Kim, Prof. Dr. Chi Kyung Kim, Prof. Dr. Seung-Hoon Lee, and Prof. Dr. Taeghwan Hyeon. Angewandte Chemie DOI: 10.1002/anie.201704904 Version of Record online: 5 JUL 2017

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Bandage with a voice (sort of)

Researchers at Empa (Swiss Federal Laboratories for Materials Testing and Research) have not developed a talking bandage despite the title (Bandage with a Voice) for a July 4, 2017 Empa press release  (also a July 4, 2017 news item on Nanowerk),

A novel bandage alerts the nursing staff as soon as a wound starts healing badly. Sensors incorporated into the base material glow with a different intensity if the wound’s pH level changes. This way even chronic wounds could be monitored at home.


Using a UV lamp, the pH level in the wound can be verified without removing the bandage and the healing process can continue unimpeded. Image: Empa / CSEM

All too often, changing bandages is extremely unpleasant, even for smaller, everyday injuries. It stings and pulls, and sometimes a scab will even start bleeding again. And so we prefer to wait until the bandage drops off by itself.

It’s a different story with chronic wounds, though: normally, the nursing staff has to change the dressing regularly – not just for reasons of hygiene, but also to examine the wound, take swabs and clean it. Not only does this irritate the skin unnecessarily; bacteria can also get in, the risk of infection soars. It would be much better to leave the bandage on for longer and have the nursing staff “read” the condition of the wound from outside.

The idea of being able to see through a wound dressing gave rise to the project Flusitex (Fluorescence sensing integrated into medical textiles), which is being funded by the Swiss initiative Nano-Tera. Researchers from Empa teamed up with ETH Zurich, Centre Suisse d’Electronique et de Microtechnique (CSEM) and University Hospital Zurich to develop a high-tech system that is supposed to supply the nursing staff with relevant data about the condition of a wound. As Luciano Boesel from Empa’s Laboratory for Biomimetic Membranes and Textiles, who is coordinating the project at Empa, explains: “The idea of a smart wound dressing with integrated sensors is to provide continuous information on the state of the healing process without the bandages having to be changed any more frequently than necessary.” This would mean a gentler treatment for patients, less work for the nursing staff and, therefore, lower costs: globally, around 17 billion $ were spent on treating wounds last year.

When wounds heal, the body produces specific substances in a complex sequence of biochemical processes, which leads to a significant variation in a number of metabolic parameters. For instance, the amount of glucose and oxygen rises and falls depending on the phase of the healing process; likewise does the pH level change. All these variations can be detected with specialized sensors. With this in mind, Empa teamed up with project partner CSEM to develop a portable, cheap and easy-to-use device for measuring fluorescence that is capable of monitoring several parameters at once. It should enable nursing staff to keep tabs on the pH as well as on glucose and oxygen levels while the wound heals. If these change, conclusions about other key biochemical processes involved in wound healing can be drawn.

The bandage reveals ist measurings in UV light.
A high pH signals chronic wounds

The pH level is particularly useful for chronic wounds. If the wound heals normally, the pH rises to 8 before falling to 5 or 6. If a wound fails to close and becomes chronic, however, the pH level fluctuates between 7 and 8. Therefore, it would be helpful if a signal on the bandage could inform the nursing staff that the wound pH is permanently high. If the bandage does not need changing for reasons of hygiene and pH levels are low, on the other hand, they could afford to wait.

But how do the sensors work? The idea: if certain substances appear in the wound fluid, “customized” fluorescent sensor molecules respond with a physical signal. They start glowing and some even change color in the visible or ultra-violet (UV) range. Thanks to a color scale, weaker and stronger changes in color can be detected and the quantity of the emitted substance be deduced.

Empa chemist Guido Panzarasa from the Laboratory for Biomimetic Membranes and Textiles vividly demonstrates how a sample containing sensor molecules begins to fluoresce in the lab. He carefully drips a solution with a pH level of 7.5 into a dish. Under a UV light, the change is plain to see. He adds another solution and the luminescence fades. A glance at the little bottle confirms it: the pH level of the second solution is lower.

Luminous molecules under UV

The Empa team designed a molecule composed of benzalkonium chloride and pyranine. While benzalkonium chloride is a substance also used for conventional medical soap to combat bacteria, fungi and other microorganisms, pyranine is a dye found in highlighters that glows under UV light. “This biomarker works really well,” says Panzarasa; “especially at pH levels between 5.5 and 7.5. The colors can be visualized with simple UV lamps available in electronics stores.” The Empa team recently published their results in the journal “Sensors and Actuators”.

The designer molecule has another advantage: thanks to the benzalkonium chloride, it has an antimicrobial effect, as researchers from Empa’s Laboratory for Biointerfaces confirmed for the bacteria strain Staphylococcus aureus. Unwelcome bacteria might potentially also be combatted by selecting the right bandage material in future. As further investigations, such as on the chemical’s compatibility with cells and tissues, are currently lacking, however, the researchers do not yet know how their sensor works in a complex wound.

Keen interest from industry

In order to illustrate what a smart wound dressing might actually look like in future, Boesel places a prototype on the lab bench. “You don’t have to cover the entire surface of wound dressings with sensors,” he explains. “It’s enough for a few small areas to be impregnated with the pyranine benzalkonium molecules and integrated into the base material. This means the industrial wound dressings won’t be much pricier than they are now – only up to 20% more expensive.” Empa scientists are currently working on this in the follow-up project FlusiTex-Gateway in cooperation with industrial partners Flawa, Schöller, Kenzen and Theranoptics.
Panzarasa now drips various liquids with different pH levels onto all the little cylinders on the wound pad prototype. Sure enough, the lighter and darker dots are also clearly discernible as soon as the UV lamp is switched on. They are even visible to the naked eye and glow in bright yellow if liquids with a high pH come into contact with the sensor. The scientists are convinced: since the pH level is so easy to read and provides precise information about the acidic or alkaline state of the sample, this kind of wound dressing is just the ticket as a diagnostic tool. Using the fluorescence meter developed by CSEM, more accurate, quantitative measure-ments of the pH level can be accomplished for medical purposes.

According to Boesel, it might one day even be possible to read the signals with the aid of a smartphone camera. Combined with a simple app, nursing staff and doctors would have a tool that enables them to easily and conveniently read the wound status “from outside”, even without a UV lamp. And patients would then also have the possibility of detecting the early onset of a chronic wound at home.

I wonder how long or even if this innovation will ever make its way into medical practice. I’m guessing this stage would be described as ‘proof of concept’ and that clinical testing is still many years away.

The metaphor in the press release’s title helped to wake me up. Thank you to whoever wrote it.

‘Superhemophobic’ medical implants

Counterintuitively, repelling blood is the concept behind a new type of medical implant according to a Jan. 18, 2017 news item on ScienceDaily,

Medical implants like stents, catheters and tubing introduce risk for blood clotting and infection — a perpetual problem for many patients.

Colorado State University engineers offer a potential solution: A specially grown, “superhemophobic” titanium surface that’s extremely repellent to blood. The material could form the basis for surgical implants with lower risk of rejection by the body.

Blood, plasma and water droplets beading on a superomniphobic surface. CSU researchers have created a superhemophobic titanium surface, repellent to blood, that has potential applications for biocompatible medical devices. Courtesy: Colorado State University

A Jan. 18, 2017 Colorado State University news release by Anne Ju Manning, which originated the news item, explains more,

t’s an outside-the-box innovation achieved at the intersection of two disciplines: biomedical engineering and materials science. The work, recently published in Advanced Healthcare Materials, is a collaboration between the labs of Arun Kota, assistant professor of mechanical engineering and biomedical engineering; and Ketul Popat, associate professor in the same departments.

Kota, an expert in novel, “superomniphobic” materials that repel virtually any liquid, joined forces with Popat, an innovator in tissue engineering and bio-compatible materials. Starting with sheets of titanium, commonly used for medical devices, their labs grew chemically altered surfaces that act as perfect barriers between the titanium and blood. Their teams conducted experiments showing very low levels of platelet adhesion, a biological process that leads to blood clotting and eventual rejection of a foreign material.

Chemical compatibility

A material “phobic” (repellent) to blood might seem counterintuitive, the researchers say, as often biomedical scientists use materials “philic” (with affinity) to blood to make them biologically compatible. “What we are doing is the exact opposite,” Kota said. “We are taking a material that blood hates to come in contact with, in order to make it compatible with blood.” The key innovation is that the surface is so repellent, that blood is tricked into believing there’s virtually no foreign material there at all.

The undesirable interaction of blood with foreign materials is an ongoing problem in medical research, Popat said. Over time, stents can form clots, obstructions, and lead to heart attacks or embolisms. Often patients need blood-thinning medications for the rest of their lives – and the drugs aren’t foolproof.

“The reason blood clots is because it finds cells in the blood to go to and attach,” Popat said. “Normally, blood flows in vessels. If we can design materials where blood barely contacts the surface, there is virtually no chance of clotting, which is a coordinated set of events. Here, we’re targeting the prevention of the first set of events.”


Fluorinated nanotubes provided the best superhemophobic surface in the researchers’ experiments.

The researchers analyzed variations of titanium surfaces, including different textures and chemistries, and they compared the extent of platelet adhesion and activation. Fluorinated nanotubes offered the best protection against clotting, and they plan to conduct follow-up experiments.

Growing a surface and testing it in the lab is only the beginning, the researchers say. They want to continue examining other clotting factors, and eventually, to test real medical devices.

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

Hemocompatibility of Superhemophobic Titania Surfaces by Sanli Movafaghi, Victoria Leszczak, Wei Wang, Jonathan A. Sorkin, Lakshmi P. Dasi, Ketul C. Popat, and Arun K. Kota. Advanced Healthcare Materials DOI: 10.1002/adhm.201600717 Version of Record online: 21 DEC 2016

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