Tag Archives: biofilms

‘Living medicine’ for lung infections

This is a fascinating approach to dealing with the problem of antibiotic resistant bacteria, from a January 19, 2023 news item on ScienceDaily,

Researchers have designed the first ‘living medicine’ to treat lung infections. The treatment targets Pseudomonas aeruginosa, a type of bacteria which is naturally resistant to many types of antibiotics and is a common source of infections in hospitals.

The treatment involves using a modified version of the bacterium Mycoplasma pneumoniae, removing its ability to cause disease and repurposing it to attack P. aeruginosa instead. The modified bacterium is used in combination with low doses of antibiotics that would otherwise not work on their own.

A January 19, 2023 Centre for Genomic Regulation press release (also on EurekAlert), which originated the news item, provides more technical detail about the work,

Researchers tested the efficacy of the treatment in mice, finding that it significantly reduced lung infections. The ‘living medicine’ doubled mouse survival rate compared to not using any treatment. Administering a single, high dose of the treatment showed no signs of toxicity in the lungs. Once the treatment had finished its course, the innate immune system cleared the modified bacteria in a period of four days. 

The findings are published in the journal Nature Biotechnology and are supported by the “la Caixa” Foundation through the CaixaResearch Health call. The study was led by researchers at the Centre for Genomic Regulation (CRG) and Pulmobiotics in collaboration with the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona and the Institute of Agrobiotechnology (IdAB), a joint research institute of Spain’s CSIC and the government of Navarre. 

P. aeruginosa infections are difficult to treat because the bacteria lives in communities that form biofilms. Biofilms can attach themselves to various surfaces in the body, forming impenetrable structures that escape the reach of antibiotics. 

P. aeruginosa biofilms can grow on the surface of endotracheal tubes used by critically-ill patients who require mechanical ventilators to breathe. This causes ventilator-associated pneumonia (VAP), a condition which affects one in four (9-27%) patients who require intubation. The incidence exceeds 50% for patients intubated because of severe Covid-19. VAP can extend the duration in intensive care unit for up to thirteen days and kills up to one in eight patients (9-13%). 

The authors of the study engineered M. pneumoniae to dissolve biofilms by equipping it with the ability to produce various molecules including pyocins, toxins naturally produced by bacteria to kill or inhibit the growth Pseudomonas bacterial strains. To test its efficacy, they collected P. aeruginosa biofilms from the endotracheal tubes of patients in intensive care units. They found the treatment penetrated the barrier and successfully dissolved the biofilms. 

“We have developed a battering ram that lays siege to antibiotic-resistant bacteria. The treatment punches holes in their cell walls, providing crucial entry points for antibiotics to invade and clear infections at their source. We believe this is a promising new strategy to address the leading cause of mortality in hospitals,” says Dr. María Lluch, Chief Scientific Officer at Pulmobiotics, co-corresponding author of the study and principal investigator at the International University of Catalonia. 

With the aim of using the ‘living medicine’ to treat VAP, the researchers will carry out further tests before reaching the clinical trial phase. The treatment is expected to be administered using a nebulizer, a device that turns liquid medicine into a mist which is then inhaled through a mouthpiece or a mask. 

M. pneumoniae is one of the smallest known species of bacteria. Dr. Luis Serrano, Director of the CRG, first had the idea to modify the bacteria and use it as a ‘living medicine’ two decades ago. Dr. Serrano is a specialist in synthetic biology, a field that involves repurposing organisms and engineering them to have new, useful abilities. With just 684 genes and no cell wall, the relative simplicity of M. pneumoniae makes it ideal for engineering biology for specific applications. 

One of the advantages of using M. pneumoniae to treat respiratory diseases is that it is naturally adapted to lung tissue. After administering the modified bacterium, it travels straight to the source of a respiratory infection, where it sets up shop like a temporary factory and produces a variety of therapeutic molecules. 

By showing that M. pneumoniae can tackle infections in the lung, the study opens the door for researchers creating new strains of the bacteria to tackle other types of respiratory diseases such as lung cancer or asthma. “The bacterium can be modified with a variety of different payloads – whether these are cytokines, nanobodies or defensins. The aim is to diversify the modified bacterium’s arsenal and unlock its full potential in treating a variety of complex diseases,” says ICREA Research Professor Dr. Luis Serrano. 

In addition to designing the ‘living medicine’, Dr. Serrano’s research team are also using their expertise in synthetic biology to design new proteins that can be delivered by M. pneumoniae. The team are using these proteins to target inflammation caused by P. aeruginosa infections. 

Though inflammation is the body’s natural response to an infection, excessive or prolonged inflammation can damage lung tissue. The inflammatory response is orchestrated by the immune system, which release mediator proteins such as cytokines. One type of cytokine – IL-10 – has well-known anti-inflammatory properties and is of growing therapeutic interest. 

Research published in the journal Molecular Systems Biology by Dr. Serrano’s research group used protein-design softwares ModelX and FoldX to engineer new versions of IL-10 purposefully optimised to treat inflammation. The cytokines were designed to be created more efficiently and to have higher affinity, meaning less cytokines are needed to have the same effect. 

The researchers engineered strains of M. pneumoniae that expressed the new cytokines and tested its efficacy in the lungs of mice with acute P. aeruginosa infections. They found that engineered versions of IL-10 were significantly more effective at reducing inflammation compared to the wild type IL-10 cytokine. 

According to Dr. Ariadna Montero Blay, co-corresponding author of the study in Molecular Systems Biology, “live biotherapeutics such as M. pneumoniae provide ideal vehicles to help overcome the traditional limitations of cytokines and unlock their huge potential in treating a variety of human diseases. Engineering cytokines as therapeutic molecules was critical to tackle inflammation. Other lung diseases such as asthma or pulmonary fibrosis could also stand to benefit from this approach.” 

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

Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms by Rocco Mazzolini, Irene Rodríguez-Arce, Laia Fernández-Barat, Carlos Piñero-Lambea, Victoria Garrido, Agustín Rebollada-Merino, Anna Motos, Antoni Torres, Maria Jesús Grilló, Luis Serrano & Maria Lluch-Senar. Nature Biotechnology (2023) DOI: https://doi.org/10.1038/s41587-022-01584-9 Published: 19 January 2023

This paper is open access.

I haven’t come across the Centre for Genomic Regulation before, so, here’s how they describe themselves from their website’s About Us, General Information page,

The Centre for Genomic Regulation (CRG) is an international biomedical research institute of excellence, created in July 2000. It is a non-profit foundation funded by the Catalan Government through the Department of Business & Knowledge and the Department of Health, the Spanish Ministry of Science & Innovation, the “la Caixa” Banking Foundation, and includes the participation of Pompeu Fabra University.  

The mission of the CRG is to discover and advance knowledge for the benefit of society, public health and economic prosperity.  

The CRG believes that the medicine of the future depends on the groundbreaking science of today. This requires an interdisciplinary scientific team focused on understanding the complexity of life from the genome to the cell to a whole organism and its interaction with the environment, offering an integrated view of genetic diseases.  

The CRG is a unique centre in Spain, based in an innovative organization research model. Group leaders at the CRG are recruited internationally and receive support from the centre to set up and run their groups. An external evaluation panel, made up of renowned leaders in the different areas, evaluates them. The result of evaluations conditions the future of the CRG scientists, no matter whether they have open-ended or time-limited contracts. This ensures the mobility and the renewal of the workforce.

There you have it.

Nano with green tea for sensitive teeth

The future will be beautiful if scientists are successful with a new DNA (deoxyribonucleic acid) sunscreen (my Aug. 3, 2017 posting) and a new dental material for people with sensitive teeth. From an Aug. 2, 2017 news item on phys.org,

An ice cold drink is refreshing in the summer, but for people with sensitive teeth, it can cause a painful jolt in the mouth. This condition can be treated, but many current approaches don’t last long. Now researchers report in the journal ACS [American Chemical Society] Applied Materials & Interfaces the development of a new material with an extract from green tea that could fix this problem—and help prevent cavities in these susceptible patients.

An Aug. 2, 2017 ACS news release, which originated the news item, describes the problem and the work in more detail,

Tooth sensitivity commonly occurs when the protective layers of teeth are worn away, revealing a bony tissue called dentin. This tissue contains microscopic hollow tubes that, when exposed, allow hot and cold liquids and food to contact the underlying nerve endings in the teeth, causing pain. Unprotected dentin is also vulnerable to cavity formation. Plugging these tubes with a mineral called nanohydroxyapatite is a long-standing approach to treating sensitivity. But the material doesn’t stand up well to regular brushing, grinding, erosion or acid produced by cavity-causing bacteria. Cui Huang and colleagues wanted to tackle sensitivity and beat the bacteria at the same time.

The researchers encapsulated nanohydroxyapatite and a green tea polyphenol — epigallocatechin-3-gallate, or EGCG — in silica nanoparticles, which can stand up to acid and wear and tear. EGCG has been shown in previous studies to fight Streptococcus mutans, which forms biofilms that cause cavities. Testing on extracted wisdom teeth showed that the material plugged the dentin tubules, released EGCG for at least 96 hours, stood up to tooth erosion and brushing and prevented biofilm formation. It also showed low toxicity. Based on these findings, the researchers say the material could indeed be a good candidate for combating tooth sensitivity and cavities.

The authors acknowledge funding from the National Natural Science Foundation of China, the Natural Science Foundation of Hubei Province of China and the Fundamental Research Funds for the Central Universities.

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

Development of Epigallocatechin-3-gallate-Encapsulated Nanohydroxyapatite/Mesoporous Silica for Therapeutic Management of Dentin Surface by Jian Yu, Hongye Yang, Kang Li, Hongyu Ren, Jinmei Lei, and Cui Huang. ACS Appl. Mater. Interfaces, Article ASAP DOI: 10.1021/acsami.7b06597 Publication Date (Web): July 13, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Nanocoating to reduce dental implant failures

Scientists at Plymouth University (UK) have developed a nanocoating that could reduce the number of dental implant failures. From a March 24, 2017 news item on Nanowerk (Note: A link has been removed),

According to the American Academy of Implant Dentistry (AAID), 15 million Americans have crown or bridge replacements and three million have dental implants — with this latter number rising by 500,000 a year. The AAID estimates that the value of the American and European market for dental implants will rise to $4.2 billion by 2022.

Dental implants are a successful form of treatment for patients, yet according to a study published in 2005, five to 10 per cent of all dental implants fail.

The reasons for this failure are several-fold – mechanical problems, poor connection to the bones in which they are implanted, infection or rejection. When failure occurs the dental implant must be removed.

The main reason for dental implant failure is peri-implantitis. This is the destructive inflammatory process affecting the soft and hard tissues surrounding dental implants. This occurs when pathogenic microbes in the mouth and oral cavity develop into biofilms, which protects them and encourages growth. Peri-implantitis is caused when the biofilms develop on dental implants.

A research team comprising scientists from the School of Biological Sciences, Peninsula Schools of Medicine and Dentistry and the School of Engineering at the University of Plymouth, have joined forces to develop and evaluate the effectiveness of a new nanocoating for dental implants to reduce the risk of peri-implantitis.

The results of their work are published in the journal Nanotoxicology (“Antibacterial activity and biofilm inhibition by surface modified titanium alloy medical implants following application of silver, titanium dioxide and hydroxyapatite nanocoatings”).

A March 27, 2017 Plymouth University press release, which originated the news item, gives more details about the research,

In the study, the research team created a new approach using a combination of silver, titanium oxide and hydroxyapatite nanocoatings.

The application of the combination to the surface of titanium alloy implants successfully inhibited bacterial growth and reduced the formation of bacterial biofilm on the surface of the implants by 97.5 per cent.

Not only did the combination result in the effective eradication of infection, it created a surface with anti-biofilm properties which supported successful integration into surrounding bone and accelerated bone healing.

Professor Christopher Tredwin, Head of Plymouth University Peninsula School of Dentistry, commented:

“In this cross-Faculty study we have identified the means to protect dental implants against the most common cause of their failure. The potential of our work for increased patient comfort and satisfaction, and reduced costs, is great and we look forward to translating our findings into clinical practice.”

The University of Plymouth was the first university in the UK to secure Research Council Funding in Nanoscience and this project is the latest in a long line of projects investigating nanotechnology and human health.

Nanoscience activity at the University of Plymouth is led by Professor Richard Handy, who has represented the UK on matters relating to the Environmental Safety and Human Health of Nanomaterials at the Organisation for Economic Cooperation and Development (OECD). He commented:

“As yet there are no nano-specific guidelines in dental or medical implant legislation and we are, with colleagues elsewhere, guiding the way in this area. The EU recognises that medical devices and implants must: perform as expected for its intended use, and be better than similar items in the market; be safe for the intended use or safer than an existing item, and; be biocompatible or have negligible toxicity.”

He added:

“Our work has been about proving these criteria which we have done in vitro. The next step would be to demonstrate the effectiveness of our discovery, perhaps with animal models and then human volunteers.”

Dr Alexandros Besinis, Lecturer in Mechanical Engineering at the School of Engineering, University of Plymouth, led the research team. He commented:

“Current strategies to render the surface of dental implants antibacterial with the aim to prevent infection and peri-implantitis development, include application of antimicrobial coatings loaded with antibiotics or chlorhexidine. However, such approaches are usually effective only in the short-term, and the use of chlorhexidine has also been reported to be toxic to human cells. The significance of our new study is that we have successfully applied a dual-layered silver-hydroxyapatite nanocoating to titanium alloy medical implants which helps to overcome these risks.”

Dr Besinis has been an Honorary Teaching Fellow at the Peninsula School of Dentistry since 2011 and has recently joined the School of Engineering. His research interests focus on advanced engineering materials and the use of nanotechnology to build novel biomaterials and medical implants with improved mechanical, physical and antibacterial properties.

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

Antibacterial activity and biofilm inhibition by surface modified titanium alloy medical implants following application of silver, titanium dioxide and hydroxyapatite nanocoatings by A. Besinis, S. D. Hadi, H. R. Le, C. Tredwin & R. D. Handy.  Nanotoxicology Volume 11, 2017 – Issue 3  Pages 327-338  http://dx.doi.org/10.1080/17435390.2017.1299890 Published online: 17 Mar 2017

This paper appears to be open access.

Slip sliding away—making surfaces bacteria can’t grasp onto

Here’s another biomimicry story with a connection to Harvard University. From a Nov. 1, 2016 Beth Israel Deaconess Medical Center (Harvard Medical School Teaching Hospital) news release (also on EurekAlert),

Implanted medical devices like catheters, surgical mesh and dialysis systems are ideal surfaces on which bacteria can colonize and form hard-to-kill sheets called biofilms. Known as biofouling, this contamination of devices is responsible for more than half of the 1.7 million hospital-acquired infections in the United States each year.

In a report published in Biomaterials today, a team of scientists at Beth Israel Deaconess Medical Center (BIDMC), the Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Sciences (SEAS) at Harvard University has demonstrated that an innovative, ultra-low adhesive coating prevented bacteria from attaching to surfaces treated with it, reducing bacterial adhesion by more than 98 percent in laboratory tests.

“Device related infections remain a significant problem in medicine, burdening society with millions of dollars in health care costs,” said Elliot Chaikof, MD, PhD, chair of the Roberta and Stephen R. Weiner Department of Surgery and Surgeon-in-Chief at BIDMC and an associate faculty member at the Wyss Institute. “Antibiotics alone will not solve this problem. We need to use new approaches to minimize the risk of infection, and this strategy is a very important step in that direction.”

The self-healing slippery surface coatings – known as ‘slippery liquid-infused porous surfaces’ (SLIPS) – were developed by Joanna Aizenberg, PhD, a Wyss Institute core faculty member, Professor of Chemistry and Chemical Biology and the Amy Smith Berylson Professor of Materials Science at SEAS at Harvard University. Inspired by the carnivorous Nepenthes pitcher plant that uses the slippery surface of its leaves to trap insects, Aizenberg engineered surface coatings that work to repel a variety of substances across a broad range of temperature, pressure and other environmental conditions. They are stable when exposed to UV light, and are low-cost and simple to manufacture. The current study is the first to demonstrate that SLIPS not only limit the ability of bacteria to adhere to surfaces, but also impede infection in an animal model.

SLIPS has been mentioned here before, most recently in a March 2, 2016 posting and before that in an Oct. 14, 2014 posting which appears to be precursor work for this latest research.

Getting back to the Nov. 1, 2016 news release, here’s more about plans for SLIPS and about recent trials,

“We are developing SLIPS recipes for a variety of medical applications by working with different medical-grade materials, ensuring the stability of the coating, and carefully pairing the non-fouling properties of the SLIPS materials to specific contaminates, environments and performance requirements,” said Aizenberg. “Here we have extended our repertoire and applied the SLIPS concept very convincingly to medical-grade lubricants, demonstrating its enormous potential in implanted devices prone to bacterial fouling and infection.”

In a series of trials, the researchers tested three SLIPS lubricants for their anti-adhesive qualities. First, they incubated disks of SLIPS-coated medical material ePTFE – a microporous form of Teflon – in a broth of Staphylococcus aureus (S. aureus), a generally harmless bacterium found in the nose and on skin, but one of the most common causes of hospital-acquired infections. After 48 hours, the three variations of SLIPS-treated disks demonstrated 98.3, 99.1 and 99.7 percent reductions in bacterial adhesion.

To test the material’s stability, the scientists performed the same experiment after soaking the SLIPS-coated samples for up to 21 days in a solution meant to simulate conditions inside a living mammal. After exposing these disks to S. aureus for 48 hours, the researchers found similar, nearly 100 percent reductions in bacterial adhesion.

Widely used clinically, medical mesh is particularly susceptible to bacterial infection. In another set of experiments to test the material’s biocompatibility, Chaikof and colleagues implanted small squares of SLIPS-treated mesh into murine models, injecting the site with S. aureus 24 hours later. Three days later, when the researchers removed the implanted mesh, they found little to no infection, compared with an infection rate of more than 90 percent among controls.

“Today, patients who receive implants often require antibiotics to keep the risk of bacterial infection at bay,” the authors wrote. “SLIPS coatings one day could obviate the widespread use of antibiotics and minimize the development of antibiotic resistant micro-organisms.”

“SLIPs have many promising medical applications that are in a very early stage of evaluation,” said Chaikof. “Clearly, there’s more work to be done before its introduction into the clinic, but this is one of a few studies that reinforces the exciting opportunities presented by this strategy to improve device performance and clinical outcomes.”

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

An immobilized liquid interface prevents device associated bacterial infection in vivo by Jiaxuan Chen, Caitlin Howell, Carolyn A. Haller, Madhukar S. Patel, Perla Ayala, Katherine A. Moravec, Erbin Dai, Liying Liu, Irini Sotiri, Michael Aizenberg, Joanna Aizenberg, Elliot L. Chaikof. Biomaterials Volume 113, January 2017, Pages 80–92  http://dx.doi.org/10.1016/j.biomaterials.2016.09.028

This paper is behind a paywall.

‘Smart dress’ for oil-degrading bacteria (marine oil spill remediation)

This July 22, 2016 news item (on Nanowerk) about bacteria and marine oil spill remediation was a little challenging (for me) to read (Note: A link has been removed),

Bionanotechnology research is targeted on functional structures synergistically combining macromolecules, cells, or multicellular assemblies with a wide range of nanomaterials. Providing micrometer-sized cells with tiny nanodevices expands the uses of the cultured microorganisms and requires nanoassembly on individual live cells (“Nanoshell Assembly for Magnet-Responsive Oil-Degrading Bacteria”).

Surface engineering functionalizes the cell walls with polymer layers and/or nanosized particles and has been widely employed to modify the intrinsic properties of microbial cells. Cell encapsulation allows fabricating live microbial cells with magnetic nanoparticles onto cell walls, which mimics natural magnetotactic bacteria.

For this study researchers from Kazan Federal University and Louisiana Tech University chose Alcanivorax borkumensis marine bacteria as a target microorganism for cell surface engineering with magnetic nanoparticles for the following reasons: (1) these hydrocarbon-degrading bacteria are regarded as an important tool in marine oil spill remediation and potentially can be used in industrial oil-processing bioreactors, therefore the external magnetic manipulations with these cells seems to be practically relevant; (2) A. borkumensis are marine Gram-negative species having relatively fragile and thin cell walls, which makes cell wall engineering of these bacteria particularly challenging.

Rendering oil-degrading bacteria with artificially added magnetic functionality is important to attenuate their properties and to expand their practical use.

[downloaded from http://pubs.acs.org/doi/abs/10.1021/acs.langmuir.6b01743]

[downloaded from http://pubs.acs.org/doi/abs/10.1021/acs.langmuir.6b01743]

A July 22, 2016 Kazan Federal University (Russia) press release (also on EurekAlert), which originated the news item, has more detail about the research,

Cell surface engineering was performed using polycation-coated magnetic nanoparticles, which is a fast and straightforward process utilizing the direct deposition of positively charged iron oxide nanoparticles onto microbial cells during a brief incubation in excessive concentrations of nanoparticles. Gram-negative bacteria cell walls are built from the thin peptidoglycan layer sandwiched between the outer membrane and inner plasma membrane, with lipopolysaccharides rendering the overall negative cell charge, therefore cationic particles will attach to the cell walls due to electrostatic interactions.

Rod-like 0.5-μm diameter Gram-negative bacteria A. borkumensis were coated with 70?100 nm [sic] magnetite shells. The deposition of nanoparticles was performed with extreme care to ensure the survival of magnetized cells.

The development of biofilms on hydrophobic surface is a very important feature of A. borkumensis cells because this is how these cells attach to the oil droplets in natural environments. Consequently, any cell surface modification should not reduce their ability to attach and proliferate as biofilms. Here, at all concentrations of PAH- magnetite nanoparticles investigated, authors of the study detected the similar biofilm growth patterns. Overall, the magnetized cells were able to proliferate and exhibited normal physiological activity.

The next generations of the bacteria have a tendency to remove the artificial shell returning to the native form. Such magnetic nanoencapsulation may be used for the A. borkumensis transportation in the bioreactors to enhance the spill oil decomposition at certain locations.

If I read this rightly, the idea, in future iterations of this research, is to destroy the oil once it’s been gathered by the biofilm. This seems a different approach where other oil spill remediation techniques have hydrophobic/oleophilic sponges absorbing the oil, which could potentially be used in the future. There are carbon nanotube sponges (my April 17, 2012 posting) and boron nitride sponges (my Dec. 7, 2015 posting).

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

Nanoshell Assembly for Magnet-Responsive Oil-Degrading Bacteria by Svetlana A. Konnova, Yuri M. Lvov, and Rawil F. Fakhrullin. Langmuir, Article ASAP DOI: 10.1021/acs.langmuir.6b01743 Publication Date (Web): June 09, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.

No more boat scraping with new coating from Duke University

There’s a lot of interest in finding ways to discourage bacteria from growing on various surfaces, for example, Sharklet, which is based on nanostructures on sharkskin, is a product being developed for hospitals (my Feb. 10, 2011 posting) and there are polymers that ‘uninvite’ bacteria at the University of Nottingham (my Aug. 13, 2012 posting).

A Jan. 31, 2013 news item on Nanowerk highlights the latest work being done at Duke University,

Duke University engineers have developed a material that can be applied like paint to the hull of a ship and will literally be able to dislodge bacteria, keeping it from accumulating on the ship’s surface. This buildup on ships increases drag and reduces the energy efficiency of the vessel, as well as blocking or clogging undersea sensors.

The team’s research was published online,

Bioinspired Surfaces with Dynamic Topography for Active Control of Biofouling by Phanindhar Shivapooja, Qiming Wang, Beatriz Orihuela, Daniel Rittschof, Gabriel P. López1, Xuanhe Zhao. Advanced Materials, Article first published online: 6 JAN 2013, DOI: 10.1002/adma.201203374

Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

The article is behind a paywall but the abstract is freely available,

Dynamic change of surface area and topology of elastomers is used as a general, environmentally friendly approach for effectively detaching micro- and macro-fouling organisms adhered on the elastomer surfaces. Deformation of elastomer surfaces under electrical or pneumatic actuation can debond various biofilms and barnacles. The bio-inspired dynamic surfaces can be fabricated over large areas through simple and practical processes. This new mechanism is complementary with existing materials and methods for biofouling control.

Duke University’s Jan. 31, 2013 news release by Richard Merritt, which originated the news item, provides more detail from the researchers,

“We have developed a material that ‘wrinkles,’ or changes it surface in response to a stimulus, such as stretching or pressure or electricity,” said Duke engineer Xuanhe Zhao, assistant professor in Duke’s Pratt School of Engineering. “This deformation can effectively detach biofilms and other organisms that have accumulated on the surface.”

Zhao has already demonstrated the ability of electric current to deform, or change, the surface of polymers.

The researchers tested their approach in the laboratory with simulated seawater, as well as on barnacles. These experiments were conducted in collaboration with Daniel Rittsch of the Duke University Marine Lab in Beaufort, N.C.

Keeping bacteria from attaching to ship hulls or other submerged objects can prevent a larger cascade of events that can reduce performance or efficiency. Once they have taken up residence on a surface, bacteria often attract larger organisms, such as seaweed and larva of other marine organisms, such as worms, bivalves, barnacles or mussels.

There are other ways to introduce efficiencies in marine transp0rtation as per my June 27, 2012 posting about Zyvex Marine and its new composites which will make for lighter vessels.

Don’t kill bacteria, uninvite them

The relentless campaign against bacteria has had some unintended consequences, we’ve made bacteria more resistant and more virulent. Researchers at the University of Nottingham (UK) have taken a different approach from attempting to eradicate or kill; they’ve discovered a class of polymers that ‘uninvites’ bacteria from their surfaces. From the Aug. 13, 2012 news item on ScienceDaily,

Using state-of-the-art technology, scientists at The University of Nottingham have discovered a new class of polymers that are resistant to bacterial attachment. These new materials could lead to a significant reduction in hospital infections and medical device failures.

Medical device associated infections can lead to systemic infections or device failure, costing the NHS £1bn a year. Affecting many commonly used devices including urinary and venous catheters — bacteria form communities known as biofilms. This ‘strength in numbers approach’ protects them against the bodies’ natural defences and antibiotics.

Experts in the Schools of Pharmacy and Molecular Medical Sciences, have shown that when the new materials are applied to the surface of medical devices they repel bacteria and prevent them forming biofilms.

There’s a video of the scientists discussing their work on this new class of polymers,

In order to find this new class of polymers, the scientists had to solve another problem first. From the Aug. 12, 2012 University of Nottingham press release,

Researchers believed there were new materials that could resist bacteria better but they had to find them. This meant screening thousands of different chemistries and testing their reaction to bacteria — a challenge which was beyond conventional materials development or any of our current understanding of the interaction of micro-organisms with surfaces.

The discovery has been made with the help of experts from the Massachusetts Institute of Technology (MIT) — who initially developed the process by which thousands of unique polymers can now be screened simultaneously.

Professor Alexander said: “This is a major scientific breakthrough — we have discovered a new group of structurally related materials that dramatically reduce the attachment of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli). We could not have found these materials using the current understanding of bacteria-surface interactions. The technology developed with the help of MIT means that hundreds of materials could be screened simultaneously to reveal new structure-property relationships. In total thousands of materials were investigated using this high throughput materials discovery approach leading to the identification of novel materials resisting bacterial attachment. This could not have been achieved using conventional techniques.”

Once they found this new class of polymers, researchers tested for effectiveness (from the Aug. 12, 2012 university press release),

These new materials prevent infection by stopping biofilm formation at the earliest possible stage — when the bacteria first attempt to attach themselves to the device. In the laboratory experts were able to reduce the numbers of bacteria by up to 96.7per cent — compared with a commercially available silver containing catheter — and were effective at resisting bacterial attachment in a mouse implant infection model. By preventing bacterial attachment the body’s own immune system can kill the bacteria before they have time to generate biofilms.

You can read more about this work in the paper the researchers have published (as well as, the news item on ScienceDaily or the University of Nottingham press release for more accessible explanations). You will need to get past a paywall (from the news item on ScienceDaily),

Andrew L Hook, Chien-Yi Chang, Jing Yang, Jeni Luckett, Alan Cockayne, Steve Atkinson, Ying Mei, Roger Bayston, Derek J Irvine, Robert Langer, Daniel G Anderson, Paul Williams, Martyn C Davies, Morgan R Alexander. Combinatorial discovery of polymers resistant to bacterial attachment. Nature Biotechnology, 2012; DOI: 10.1038/nbt.2316

This research reminded me of Sharklet, a product being developed in the US for use in hospitals. Designed to mimic sharkskin, the product discourages bacteria from settling on its surface. It was featured in my Feb. 10, 2011 posting.

Dental fillings that improve your teeth

If you have lousy teeth, this is exciting news. From the May 2, 2012 news item on Nanowerk (I have removed a link),

Scientists using nanotechology at the University of Maryland School of Dentistry have created the first cavity-filling composite that kills harmful bacteria and regenerates tooth structure lost to bacterial decay. [emphasis mine]

Rather than just limiting decay with conventional fillings, the new composite is a revolutionary dental weapon to control harmful bacteria, which co-exist in the natural colony of microorganisms in the mouth, says professor Huakun (Hockin) Xu, PhD, MS. [emphasis mine]

While the possibilities are promising, I find the idea of a weapon in my mouth disconcerting. (They might want to check out their metaphors a little more closely.) Moving on, there’s a little more detail about this new composite  (from the news item),

Fillings made from the School of Dentistry’s new nanocomposite, with antibacterial primer and antibacterial adhesive, should last longer than the typical five to 10 years, though the scientists have not thoroughly tested longevity. Xu says a key component of the new nanocomposite and nano-structured adhesive is calcium phosphate nanoparticles that regenerate tooth minerals. The antibacterial component has a base of quaternary ammonium and silver nanoparticles along with a high pH. The alkaline pH limits acid production by tooth bacteria.

“The bottom line is we are continuing to improve these materials and making them stronger in their antibacterial and remineralizing capacities as well as increasing their longevity,” Xu says.

The new products have been laboratory tested using biofilms from saliva of volunteers. The Xu team is planning to next test its products in animal teeth and in human volunteers in collaboration with the Federal University of Ceara in Brazil.

The folks at the enewsparkforest blog are not quite so sanguine about this dental development as per their May 3, 2012 posting on the topic (I have removed llinks),

A study conducted in 2008 and confirmed by another study in 2009 shows that washing nano-silver textiles releases substantial amounts of the nanosilver into the laundry discharge water, which will ultimately reach natural waterways and potentially poison fish and other aquatic organisms. A study found nanosilver to cause malformations and to be lethal to small fish at various stages of development since they are able to cross the egg membranes and move into the fish embryos. A 2010 study by scientists at Oregon State University and in the European Union highlights the major regulatory and educational issues that they believe should be considered before nanoparticles are used in pesticides.

As Dexter Johnson in his May 3, 2012 posting on his Nanoclast blog (on the Institute for Electrical and Electronics Engineers website) notes,

The researchers are continuing with their animal and human testing with the nanocomposite. Given that some sectors of the public are concerned about the potential risks of silver nanoparticles, they should probably take a look at the issue as part of their research.

This is not unreasonable especially in light of the concern some folks have had over mercury in dental fillings. Sufficient concern by the way to occasion this cautionary note from Health Canada (from the Mercury and Human Health webpage on their website),

Minimizing Your Risk

Elemental mercury from dental fillings does not generally pose a health risk. There is, however, a fairly small number of people who are hypersensitive to mercury. While Health Canada does not recommend that you replace existing mercury dental fillings, it does suggest that when the fillings need to be repaired, you may want to consider using a product that does not contain mercury.

Pregnant women, people allergic to mercury and those with impaired kidney function should avoid mercury fillings. Whenever possible, amalgam fillings should not be removed when you are pregnant because the removal may expose you to mercury vapour. When appropriate, the primary teeth of children should be filled with non-mercury materials.

Side note: I find it interesting that while Health Canada has not banned the use of mercury in fillings, it does advise against adding more mercury-laced fillings to your mouth and/or using them in your children’s primary teeth, if possible.

Getting back to silver nanoparticles in our mouths, I reiterate Dexter’s suggestion.

Could nanoparticles in your mouthwash affect for your cells?

The first news item I’m going to highlight was posted on Nanowerk, March 8, 2012 and is focused on the use of silver nanoparticles in mouthwashes and dentures to prevent yeast infections,

Yeasts which cause hard-to-treat mouth infections are killed using silver nanoparticles in the laboratory, scientists have found. These yeast infections, caused by Candida albicans and Candida glabrata target the young, old and immuno-compromised. Professor Mariana Henriques, University of Minho [Portugal], and her colleagues hope to test silver nanoparticles in mouthwash and dentures as a potential preventative measure against these infections.

Professor Henriques and her team, who published their research in the Society for Applied Microbiology’s journal Letters in Applied Microbiology(“Silver nanoparticles: influence of stabilizing agent and diameter on antifungal activity against Candida albicans and Candida glabrata biofilms”), looked at the use of different sizes of silver nanoparticles to determine their anti-fungal properties …

The scientists used artificial biofilms in conditions which mimic those of saliva as closely as possible. They then added different sizes and concentrations of silver nanoparticles and found that different sizes of nanoparticles were equally effective at killing the yeasts. Due to the diversity of the sizes of nanoparticles demonstrating anti-fungal properties the researchers hope this will enable the nanoparticles to be used in many different applications.

Some researchers have expressed concerns around the safety of nanoparticle use but the authors stress this research is at an early stage and extensive safety trials will be carried out before any product reaches the market. [emphasis mine]

Following on the notion of safety and gargling silver nanoparticles, coincidentally, there was another news item also dated March 8, 2012 on Nanowerk, this one about the impact that nanoparticles may have on nutrient uptake,

Nanoparticles are everywhere. From cosmetics and clothes, to soda and snacks. But as versatile as they are, nanoparticles also have a downside, say researchers at Binghamton University and Cornell University in a recent paper published in the journal Nature Nanotechnology (“Oral exposure to polystyrene nanoparticles affects iron absorption”). These tiny particles, even in low doses, could have a big impact on our long-term health.

According to lead author of the article, Gretchen Mahler, assistant professor of bioengineering at Binghamton University, much of the existing research on the safety of nanoparticles has been on the direct health effects. But what Mahler, Michael L. Shuler of Cornell University and a team of researchers really wanted to know was what happens when someone gets constant exposure in small doses – the kind you’d get if you were taken a drug or supplement that included nanoparticles in some form. [e.g. silver nanoparticles in your mouthwash or on your dentures]

“We thought that the best way to measure the more subtle effects of this kind of intake was to monitor the reaction of intestinal cells,” said Mahler. “And we did this in two ways: in vitro, through human intestinal-lining cells that we had cultured in the lab; and in vivo, through the intestinal linings of live chickens. Both sets of results pointed to the same thing – that exposure to nanoparticles influences the absorption of nutrients into the bloodstream.”

As for why the researchers focused on iron and tested polystyrene nanoparticles (from the news item),

The uptake of iron, an essential nutrient, was of particular interest due to the way it is absorbed and processed through the intestines. The way Mahler and the team tested this was to use polystyrene nanoparticles because of its easily traceable fluorescent properties.

“What we found was that for brief exposures, iron absorption dropped by about 50 percent,” said Mahler. “But when we extended that period of time, absorption actually increased by about 200 percent. It was very clear – nanoparticles definitely affects iron uptake and transport.”

While acute oral exposure caused disruptions to intestinal iron transport, chronic exposure caused a remodeling of the intestinal villi – the tiny, finger-like projections that are vital to the intestine’s ability to absorb nutrients – making them larger and broader, thus allowing iron to enter the bloodstream much faster.

As to whether these changes are good or bad the researchers don’t speculate. They do have plans for more testing,

calcium,
copper,
zinc, and
fat-soluble vitamins A, D, E and K

They don’t mention any changes in the types of nanoparticles they might be testing in future.

In any event, our bodies have changed a lot over the centuries, you just have to visit a pyramid in Egypt or a museum that holds medieval armour to observe that humans were once much shorter than we are today.