Smart biocomposite

Chemists have taught implant materials to control their antibacterial activity

Natalia Safronova, "Scientific Russia"

Bacterial infections often occur on implants and prostheses, and therefore scientists are looking for different ways to give their surface antibacterial properties. Researchers from the D.I. Mendeleev Russian Technical Technical University, N.N. Priorov NMIC and the University of Crete have developed a new material for prostheses – a polymer biocomposite that contains a powerful antibiotic amikacin. At the same time, the antibiotic leaves the material only during a bacterial attack, and the intensity of its release can be controlled by changing the thickness of the composite.

The results of the study are published in the journal Polymer International (Dyatlov et al., Immobilization of amikacin on dextran: biocomposite materials that release an antibiotic in the presence of bacterial dextranase).

Bacteria that provoke infections can settle on the surface of different implants. Thus, approximately 2-3% of patients with prosthetic heart valves develop their bacterial inflammation, called endocarditis. There are different ways to stop the infection: taking antibiotics, surgery, modification of the surface of the prostheses with silver particles with a pronounced antibacterial effect. One of the most promising among them is the creation of a prosthetic material with an immobilized, that is, an antibiotic embedded on its surface. And ideally, the antibiotic should come out of the material only in the presence of infection – so, on the one hand, it will not end too quickly, and on the other, it will not provoke toxic side effects. 

"We immobilized a broad–spectrum antibiotic amikacin on a polysaccharide called dextran, and then we made a biocomposite based on this material," says the first author of the work, Professor of the Russian Technical Technical University Valery Dyatlov. "Humans do not have dextranase, an enzyme that decomposes dextran, but bacteria produce it. Therefore, as soon as they attack the biocomposite, their enzymes begin to decompose it, and chemical compounds of amikacin come out of the composite, which also, like pure amikacin, have a pronounced antibacterial effect. So we have developed a material that is able to release an antibiotic point-by-point in response to a bacterial attack."

To create biocomposites, scientists used two xenomaterials – the so-called cell matrices obtained after chemical treatment of living tissues. In this work, xenomaterials based on the pericardium (the tissue of the outer shell of the heart) and the glissone capsule (the tissue of the liver shell), which have long been used in medicine to create prostheses, were used.

Intensity to order

"We synthesized the biocomposite in several stages," says one of the authors of the work, an employee of the RCTU Anna Luss. – First dextran was treated with epichlorohydrin, and so epoxy groups appeared on it – due to them dextran bound to amikacin, and a gel was obtained. Then the gel was applied to the xenomaterials, and it was chemically stitched with them, impregnating the xenomaterials to a certain depth. The thickness of the resulting biocomposite from the pericardium was 0.42 mm, and from the glissone capsule – 0.15 mm, while the depth of penetration of dextran in them was 0.10 and 0.03 mm, respectively."

In model experiments with pure dextranase, scientists have shown that from a biocomposite based on a glissone capsule, all amikacin is released in 2 hours, and from a composite based on the pericardium – in 24 hours. The antibacterial activity of the new materials was also tested on bacteria S.aureus, B.subtilis and S.Pyogenes. The composites were brought into contact with bacterial cultures grown in a Petri dish, and after 24 hours, the suppression of bacterial growth was observed in the area around the xenomaterials, as well as under them and on their surface. In addition, biocomposites were injected under the skin of laboratory rabbits – there were no bacterial pathogens, and even after 12 days, all amikacin remained inside the xenomaterial. In addition, the researchers found out what factors determine the rate of antibiotic release.

"It turned out that the speed of response to a bacterial attack is determined by the rate of diffusion of the hydrolysis products of dextran modified with amikacin – that is, the reaction took place somewhere in the depth of the xenomaterial, amikacin glycosides were released, and then they should reach the surface, and the speed of this process determines the overall rate of antibiotic release," says the head of the Department of Biomaterials of the RCTU and one one of the authors of the work, Professor Mikhail Shtilman. – If this stage is limiting, it turns out that the rate of antibiotic release is determined by the thickness of the gel layer impregnated with the xenomaterial. If you want the substance to be released slowly and the implant to withstand many bacterial attacks, then you make the biocomposite thicker. And if doctors are sure that it is not necessary to count on a series of attacks, then you make the composite thinner, from which the release of the antibiotic will be more abrupt and at a high speed."    

Thus, scientists have not only developed a material with regulated antibacterial properties, but also found a way to control the intensity of this effect. Now they plan to continue experiments with other xeno-fabrics, and the developed material, according to the researchers, will be useful for creating new implants resistant to antibacterial infections.

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