Viruses, nanosilver and new polymers will kill bacteria from endoprostheses

Infections after the insertion of prostheses or medical equipment are one of the most difficult complications to treat in the hospital. Bacteria are difficult to get rid of and often the catheter or even the endoprosthesis must be removed. However, scientists have developed coatings to prevent bacteria from settling on the surfaces of endoprostheses or catheters. Also in Poland, new materials are being worked on to prevent this type of infection.

Infections after insertion of a joint prosthesis are one of the most serious postoperative complications, and as a result of which it is often necessary to remove it. As the doctors from the Department of Orthopedics and Traumatology of the Movement of the First Medical Faculty of the Medical University of Warsaw (Dr. Ireneusz Babiak, Dr. med. Michał Kowalewski and Dr. Grzegorz Szczęsny) in the periodical Infections, these complications usually show quite accurately the condition of the hospital – the greater diligence while observing medical and operational procedures, the less such infections are.

They usually occur in the postoperative period, although in the Rheumatology periodical, Dr. Tomasz Okoń and his team discuss a case of fungal arthritis of the knee that occurred 9 years after endoprosthetics of this joint. At the same time, such inflammations are a costly disease to cure – according to data from the middle of the current decade, the treatment of an infected patient cost PLN 50. up to 140 thousand USD in the United States and 350 thousand. up to 500 thousand euro in Germany. Usually, in the case of the most expensive treatment, it is necessary to remove the endoprosthesis and after healing the new placement. They are known, among others cases of infection and the need to remove endoprostheses in hospitals in Warsaw and Łódź in the last year.

The killer bacteriophage will help

Not surprisingly, doctors, biologists and virologists have joined forces to reduce the possibility of nosocomial infections involving endoprostheses caused by bacteria and fungi as much as possible. Endoprostheses, to a lesser extent pacemakers, or even catheters are a great environment for the development of microorganisms. They easily multiply on their surface, creating biofilms, i.e. bacterial layers, and their removal is very difficult.

Biofilm is a sticky, thin structure composed of many strains and species of bacteria as well as organic and inorganic compounds. It is created, among others, by Staphylococcus, Enterococcus and Escherichia coli bacteria. It protects microorganisms against the influence of environmental factors and substances that could destroy them, e.g. antibiotics. Once formed, it is very difficult to remove, especially on the surface of implants, medical equipment or endoprostheses. Hence, the work of scientists is aimed at creating such surface protections that bacteria and fungi cannot colonize them.

The most interesting and advanced solution was presented by a team of scientists from Clemson University in South Carolina and the University of Southern Mississippi led by Prof. Mark W. Urban, a Pole working in the USA. In their safety system for hospital equipment and endoprostheses, all these devices would be covered with a layer of bacteria-destroying viruses – bacteriophages.

Bacteriophages are viruses with complex shapes – club-shaped, rod-shaped or polyhedral – usually affecting one or two species of bacteria; some can only attack one strain. Scientists in the US have developed a thin film – a bacteriophage film – that can cover the surface of hospital equipment, whether it is made of metal, various types of plastic or Teflon. When a bacterium hits this type of film, the bacteriophages deposited on it inject nucleic acid into its interior. The bacterial cell, incorporating it into its nucleic acid structure, begins to copy the bacteriophages, which causes its destruction. The progeny bacteriophages, in turn, infect other bacterial cells.

How to make a bacteriophage film

During the research, scientists used a thin film covered with Φ11 and T1 bacteriophages, deposited on the surface of various types of polymers, imitating the casings or working parts of endoprostheses and medical equipment. As proven, this solution is very effective in the case of attack of endoprostheses or devices by Staphylococcus and Escherichia coli bacteria. The effectiveness was not dependent on the type of substrate – phages felt equally well on various types of plastic and on Teflon coatings.

However, creating a bacteriophage film that can function properly on all surfaces is quite complicated. First, it is necessary to heat the surface of the most commonly used types of plastics for the production of such devices – polyethylene (PE) and polytetrafluoroethylene (PTFE) and apply a solution with T1 and Φ11 phages to the heated surface. After applying the film for several hours, covering it with a solution containing a high concentration of human pathogens Escherichia coli and Staphylococcus causes that bacteriophages completely purify the solution of bacteria, destroying them quickly. Bacterial biofilm, which allowed other microorganisms to settle, is also not formed on the surface of the device. The first tests with colonies containing a large number of different bacterial strains also showed positive results. The only difficulty is the control of the number of bacteriophages, which multiply very quickly in the case of high concentration of bacteria. Another two-year study is to be devoted to mastering the control of the bacteriophage population. The first tests of new plastics with bacteriophage film should be expected in mid-2015.

Bacteria do not like new polymers

In turn, a team of scientists from the Massachussets Institute of Technology, led by prof. Krystyn Van Vliet and prof. Michael Rubner took a different path. Back in 2008, these scientists found that soft plastics are not the best environment for bacteria – microorganisms are more suited to hard plastics. As a result, two years later, they developed a chemical antibacterial coating that is now undergoing clinical trials. Scientists from MIT concluded that the most important thing is to create a solution that will prevent biofilm from depositing on the surface of endoprostheses and medical devices.

Scientists investigated the conditions of deposition on medical devices of the basic microbial biofilm – Staphylococcus and Escherichia coli. It turned out that in the initial stage of infection, bacteria are very sensitive to the type and properties of the surface on which they settle. As it turned out, on a soft surface, additionally covered with a hydrated gel, bacteria were deposited very rarely, and on hard surfaces, often with antibacterial protection in the form of various types of plastic milling, biofilm was formed relatively quickly.

After two years of study, MIT scientists developed a two-layer coating consisting of a soft polymer inside and an outer layer of a solidified gel containing silver nanoparticles. Such a coating is currently in the testing phase. The results are promising – during the testing of endoprostheses with this type of coating, no bacterial infections or the formation of biofilms were observed.

Apart from creating bactericidal coatings, another solution preventing infections of endoprostheses and hospital equipment such as catheters is the use of new type materials, e.g. complex polymers or new generation polymer-metal structures. Such research is also carried out in Poland, where the research team of Dr. Eng. Joanna Ryszkowska from the Institute of Materials Science and Engineering of the Warsaw University of Technology. According to the researchers, it is important to create a polymer that would hinder the deposition of bacteria and fungi on the surface of the devices as much as possible. During the research, it was possible to obtain several types of polymers that prevent the formation of a bacterial layer. Testing the resistance of these materials is ongoing.

Tekst: Marek Mejssner

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