Tag Archives: bacterial infection

Killer graphene spikes to kill bacteria on medical implants

Implants of all kinds (hip replacements, knee replacements, etc.) seem to be on the rise and along with that an increasing number of infections. A Swedish research team announces a technology that could make implants safer in an April 16, 2018 news item on Nanowerk,

A tiny layer of graphene flakes becomes a deadly weapon and kills bacteria, stopping infections during procedures such as implant surgery. This is the findings of new research from Chalmers University of Technology, Sweden, recently published in the scientific journal Advanced Materials Interfaces (“Vertically Aligned Graphene Coating is Bactericidal and Prevents the Formation of Bacterial Biofilms”).

An April 16, 2018 Chalmers University of Technology press release (also on EurekAlert), which originated the news item, provides more detail about the scope of the problem and the proposed solution (Note: A link has been removed),

Operations for surgical implants, such as hip and knee replacements or dental implants, have increased in recent years. However, in such procedures, there is always a risk of bacterial infection. In the worst case scenario, this can cause the implant to not attach to the skeleton, meaning it must be removed.

Bacteria travel around in fluids, such as blood, looking for a surface to cling on to. Once in place, they start to grow and propagate, forming a protective layer, known as a biofilm.

A research team at Chalmers has now shown that a layer of vertical graphene flakes forms a protective surface that makes it impossible for bacteria to attach. Instead, bacteria are sliced apart by the sharp graphene flakes and killed. Coating implants with a layer of graphene flakes can therefore help protect the patient against infection, eliminate the need for antibiotic treatment, and reduce the risk of implant rejection. The osseointegration – the process by which the bone structure grow to attach the implant – is not disturbed. In fact, the graphene has been shown to benefit the bone cells.

Chalmers University is a leader in the area of graphene research, but the biological applications did not begin to materialise until a few years ago. The researchers saw conflicting results in earlier studies. Some showed that graphene damaged the bacteria, others that they were not affected.

“We discovered that the key parameter is to orient the graphene vertically. If it is horizontal, the bacteria are not harmed” says Ivan Mijakovic, Professor at the Department of Biology and Biological Engineering.

The sharp flakes do not damage human cells. The reason is simple: one bacterium is one micrometer – one thousandth of a millimeter – in diameter, while a human cell is 25 micrometers. So, what constitutes a deadly knife attack for a bacterium, is therefore only a tiny scratch for a human cell.

“Graphene has high potential for health applications. But more research is needed before we can claim it is entirely safe. Among other things, we know that graphene does not degrade easily” says Jie Sun, Associate Professor at the Department of Micro Technology and Nanoscience.

Good bacteria are also killed by the graphene. But that’s not a problem, as the effect is localised and the balance of microflora in the body remains undisturbed.

“We want to prevent bacteria from creating an infection. Otherwise, you may need antibiotics, which could disrupt the balance of normal bacteria and also enhance the risk of antimicrobial resistance by pathogens” says Santosh Pandit, postdoc at Biology and Biological Engineering.

Vertical flakes of graphene are not a new invention, having existed for a few years. But the Chalmers research teams are the first to use the vertical graphene in this way. The next step for the research team will be to test the graphene flakes further, by coating implant surfaces and studying the effect on animal cells.

Chalmers cooperated with Wellspect Healthcare, a company which makes catheters and other medical instruments, in this research. They will now continue with a second study.

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

Vertically Aligned Graphene Coating is Bactericidal and Prevents the Formation of Bacterial Biofilms by Santosh Pandit, Zhejian Cao, Venkata R. S. S. Mokkapati, Emanuele Celauro, Avgust Yurgens, Martin Lovmar, Fredrik Westerlund, Jie Sun, Ivan Mijakovic. Advanced Materials Interfaces Volume5, Issue7 April 9, 2018 Pages 1701331 [sic] https://doi.org/10.1002/admi.201701331 First published [online]: 2 February 2018

This paper is behind a paywall.

Finally, here’s a ‘killer spikes’ video made available by Chalmers University of Technology,

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.