MISiS: Technology of simultaneous application of antibacterial and bioactive coatings on titanium implants

Main article: Bone implantation

2023

Confirmation of technology effectiveness in in vivo tests

The effectiveness of the titanium implant coating technology for reconstructive surgery previously proposed by NUST MISIS scientists was confirmed by specialists of the National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya. The results of in vivo tests showed that after special treatment, the interaction of the implant with bone tissue, its antibacterial and antifungal activity, is improved. This was announced on September 14, 2023 at the university. The technology does not require expensive equipment and can be carried out directly in hospitals and surgical centers.

One of the optimal and easily scalable methods for modifying the implant surface is plasma electrolytic oxidation (PEO) when titanium articles are treated in a high voltage electrolyte.

Due to the separation gaseous of oxygen from the melt during time processing, metal a microporous oxide coating is formed on the substrate, the microstructure of which is better adapted to bone tissue than smooth titanium. The size, shape and size distribution of the pores also have a significant effect on cell adhesion, spread, proliferation and differentiation. Micropores can also serve as a reservoir for loading various biologically active substances: growth factors, bactericides, etc., said the author of the study Anastasia Popova, engineer of the scientific and educational center of self-propagating high-temperature synthesis (NOC SVS) MISIS-ISMAN, graduate student of the Department of Powder Metallurgy and Functional Coatings of MISIS University.

To improve the biological activity of the material during the PEO treatment, functional elements such as Cu, Na, P, Ca, Si, O were added to the electrolyte composition. According to the study performer, iPhD undergraduates of the NUST MISIS "Biomaterial Science" program Daria Advakhova, copper effectively inactivates Gram-positive and Gram-negative bacteria, preventing the formation of harmful biofilms. To accelerate bone formation around the implant, the scientists loaded the surface with BMP-2 protein, the most studied bone morphogenetic protein used in orthopedic surgery.

Bioactivity and biocompatibility assessments were performed on a model of titanium implants specifically designed for the skull of mice. Tests have shown that the BMP-2 protein significantly accelerates the formation of new bone tissue. We observed marked bone remodeling, osteoconduction, and osteogenesis, said co-author of the study, Doctor of Biological Sciences, Professor Anna Karyagina, Chief Researcher, Laboratory of Biologically Active Nanostructures, NF Gamaleya Research Institute.

Although the process of plasma-electrolytic oxidation is relatively well studied, scientists at MISIS University have identified an interesting structural feature that has not been discussed in detail before. Using transmission electron microscopy, it was possible to find out that the functional elements are not distributed throughout the coating volume, but are concentrated on the surface in the form of bioglass due to the technical features of the process.

Cells Ca, P, Na, K, Si, and O introduced into the electrolyte determine the bioactivity of the implant due to ion exchange occurring at the border of the surface with the physiological medium. This discovery is not only fundamental, but also practical. Bio-glasses are amorphous materials that can bind to both solid and soft tissues and can be used in porous implants to promote adhesion and proliferation of bone cells. They dissolve at a rate comparable to that of new bone tissue formation and can be used as drug delivery systems. By selecting coating formation modes and electrolyte composition, we can form a thin layer of bioglass with the composition necessary for a particular application, added co-author of the study, Ph.D. Konstantin Kuptsov, senior researcher at the NOC SWS MISIS-ISMAN.

The study was carried out with the support of the Russian Scientific Foundation (No. 20-19-00120-Π) and the strategic project of the University of MISIS "Biomedical Materials and Bioengineering" under the leadership of Doctor of Medical Sciences Dmitry Shtansky, Chief Researcher of the NOC SWS MISIS-ISMAN.

Imparting Bioactive and Bactericidal Properties to the Material by Plasma Electrolytic Oxidation

Scientists at the University of Science and Technology MISIS have proven the possibility of simultaneously applying an antibacterial and bioactive coating to titanium implants. This was announced on March 13, 2023 by Zdrav.Expert representatives of the university.

According to them, at the time of the release of the material, the technology has no direct analogues, it is much simpler and cheaper than the previously used two-stage complex process. In addition, the coating method is tested on highly porous titanium articles having closer mechanical characteristics to bone than classical endoprostheses.

Russian scientists proposed a method for the manufacture of bone implants combining antibacterial and bioactive properties

As the scientists explained, earlier, when modifying implants, the first stage was to apply a bioactive coating (calcium, phosphorus, silicon) on a solid titanium substrate, which improves engraftability. The second step was to apply copper having bactericidal properties. At the same time, it is important to comply with a certain concentration of copper nanoparticles, otherwise, if there is an excess, the coating will be toxic, and if there is a shortage, it will not be bactericidal.

Among the advantages of modified implants compared to existing ones on the market in NUST MISIS were named:

• simultaneous combination of antibacterial and bioactive properties. Although these characteristics are generally thought to be mutually exclusive. In experiments, it has been found that the plasma electrolytic oxidation method imparts the desired properties to the coating in a single step.
• simple manufacturing technology. Medical centers will not need specific expensive equipment;
• possibility of creating a personal implant according to individual parameters of the patient using 3D printing with titanium powder.

"Such a surface modification is aimed at giving implants improved regenerative properties that stimulate the formation of healthy bone tissue at the implant border in the area of ​ ​ a bone defect," said Anastasia Popova, co-author of the study, graduate student at NUST MISIS. - The method of plasma electrolytic oxidation is used as a method of surface modification for the first time for highly porous metal implants with multimodal pore distribution. To impart bioactive, bactericidal and antifungal characteristics to the material, various functional additives are added to the electrolytes. For better and faster integration, porous coatings will be saturated with a growth factor such as BMP-2 protein. "

The materials being developed are intended for applications in personalized medicine as implants for craniofacial surgery. Further modification of implants by growth factors and a study of osteointegration ability will be carried out by specialists of the N.F. Gamalei. The State Scientific Center for Applied Microbiology and Biotechnology (Obolensk) will study the antibacterial and antifungal resistance of coating to pathogens with antibiotic resistance.

Further work on the project will take place in conjunction with the scientific team of the CSIR-Central Electrochemical Scientific Institute, Tamilnadu, Karraikudi, India.

See also

Import substitution of medical devices

Price regulation of medical devices in Russia

Export of medical devices from Moscow

Export of medical devices from Russia

Brain implant

Breast implants

Dental implants

Buttock implants

Spondylodesis implants (global market)

Heart Implants (Global Market)

Bone implantation