Engineering Surface Patterns to Combat Infection
In a time when bacterial resistance to current antibiotics is rising, medical science needs all the new tools it can fit into its infection-fighting toolbox. In addition to new antimicrobial drugs, and repurposing older drugs to fight bacteria, new technologies are under development that may be able to stop infection without any drugs whatsoever.
Researchers at the University of Nottingham have come up with a way to halt, and even prevent infections on plastic medical devices, which relies on alterations to the surface of the plastic itself. Their research could not only help to prevent infection through medical devices, but could also lead to technologies that help the body to eliminate bacteria before infections take hold.
The Problem
The World Health Organization has declared antimicrobial resistance (AMR) one of the top ten global public health threats. It causes millions of deaths each year around the world, many of these in healthcare settings. Antibiotic resistant infections can be an even bigger problem in hospitals, as patients can contract healthcare-associated infections (HAIs), which can worsen other conditions and lengthen hospital stays.
One of the ways that antimicrobial-resistant HAIs develop is through the use of plastic medical devices, such as catheters and breathing tubes. Bacteria produce biofilms, which protect the bacteria from the body’s natural defenses. When bacteria come into contact with medical devices made from plastic, they form biofilms on the plastic. When this happens, the bacteria become very difficult to treat with antibiotics.
This problem is compounded by the ubiquity of plastics in hospital settings, from catheters and breathing tubes to IV bags, syringes, tubing, and more.
Existing Technologies
Researchers have already experimented with introducing antimicrobial agents to the materials used to make medical devices. However, this idea has problems of its own, including a higher cost, and the fact that not all antimicrobial agents are effective against all types of infection. In addition, the anti-microbial properties of such devices are limited in the long term. On top of that, biofilms may develop resistance to the antimicrobial agents used in these devices, driving, rather than preventing, antimicrobial resistance.
Biofilm-Disrupting Surface Design
When bacteria arrive on a surface, they first attach reversibly, then irreversibly. After that, they organise themselves into microcolonies, and then form a biofilm. The biofilm allows for intercellular cooperation, nutrient capture and sharing, and strengthens cells against antimicrobial agents and the body’s immune defenses.
The formation of a biofilm depends on regulatory decisions made by sophisticated, integrated surface sensing networks. Altering the design of the surface of a plastic device can disrupt the formation of biofilm.
At the University of Nottingham, researchers identified ways to alter the surface of various plastics commonly used in hospitals, in order to hinder the formation of biofilm. In the study, the team created 2,176 surface designs on various plastics in common use in hospitals, including polyurethane, then studied their effectiveness in disrupting biofilm formation.
Professor Williams of the School of Life Sciences says, “Our findings could help to reduce the high number of infections in healthcare settings associated with medical devices. Not only could this method prevent bacteria sticking but also activate the body’s immune system to kill any bacteria that have stuck to the surface.”
Professor Morgan Alexander from the School of Pharmacy said, “Using physically patterned surfaces has the advantage over coating approaches that it can be applied to existing device materials, reducing the barrier to commercial application. Our discovery could save the NHS a lot of money.”
Professor Alexander, along with others from the School of Computer Science, and Jan de Boer of the Netherlands, partnered with Professor Williams in the study.
Study Specifics
The University of Nottingham team leveraged machine learning to identify the most relevant topographical elements, and to extract generalisable design rules for their test surface patterns. It was hoped that these rules could predict surface microtopographies that would prove resistant to biofilm formation. Ultimately, the researchers chose 2,176 of these microtopographies as surface patterns, printing them onto polyurethane and other plastics. The study included not only different surface patterns, but also different types of commonly used hospital plastics, and a variety of bacteria.
The study found that different topographies can inhibit biofilm formation in two primary ways. First, anti-adhesive surfaces keep bacteria from attaching, which prevents biofilm from forming. Other topographies were discovered to have bactericidal effects. The surface designs in the study mimicked certain surface forms in nature, including shark skin scales, insect wings, and the leaves and flowers of certain plants.
Some of the patterns reduced colonization by pathogens associated with medical device-related infections by up to fifteen fold, when compared to a flat polymer surface. As a result, the study shows the potential of simple topographical patterning for preventing biofilm associated infections.
Helping the Body to Fight Infection
The surface pattern that showed the best potential for inhibiting biofilm formation involved small crevices in raised surface patterns. Researchers found that the crevices trapped the bacterial cells and tricked them into producing a lubricant that prevented their sticking to the plastic surface. This, in turn, prevented biofilm formation. The experiment results suggested that in a human model, this design would make it easier for immune defense cells to clear out the bacteria and prevent infection.
Future Applications
Researchers hope to expand their study to practical medical devices, in collaboration with medical device companies.