rus
Issue #6/2020
G. V. Odintsova, Yu. Yu. Karlagina 1, V. V. Romanov, R. M. Yatsuk, E. E. Egorova, Е. А. Zernitskaya, А. I. Yaremenko, G. N. Chernenko, S. G. Gorny, V. P. Veiko
Laser Technology for Structuring the Surface of Dental Titanium Implants. Part 2
Laser Technology for Structuring the Surface of Dental Titanium Implants. Part 2
DOI: 10.22184/1993-7296.FRos.2020.14.6.510.519
The first part of this research deals with development of a method for the laser formation of a biocompatible surface morphology of titanium dental implants, providing a hydrophilic surface structure that has both micro- and nanorelief. In this second part of the study, we present the results of preclinical tests of the laser-induced relief’s biocompatibility. The implants with the modified surface showed an advanced proliferation of multipotent mesenchymal stromal cells over the entire surface area, even in open pores. Implants with such a surface also showed positive results of osseointegration in a living organism: three months after implantation, a new mature bone tissue is formed in the previously destroyed bone area, which is directly connected to the implant surface. The technology based on this method has been adopted into the production of a dental milling center for a full production cycle and a plant belonging to the ORTOS group of companies.
The first part of this research deals with development of a method for the laser formation of a biocompatible surface morphology of titanium dental implants, providing a hydrophilic surface structure that has both micro- and nanorelief. In this second part of the study, we present the results of preclinical tests of the laser-induced relief’s biocompatibility. The implants with the modified surface showed an advanced proliferation of multipotent mesenchymal stromal cells over the entire surface area, even in open pores. Implants with such a surface also showed positive results of osseointegration in a living organism: three months after implantation, a new mature bone tissue is formed in the previously destroyed bone area, which is directly connected to the implant surface. The technology based on this method has been adopted into the production of a dental milling center for a full production cycle and a plant belonging to the ORTOS group of companies.
Теги: dental implants implant success in vitro in vivo laser surface treatment preclinical studies wall-to-wall production. дентальные имплантаты доклинические исследования лазерная обработка поверхности полный цикл производства приживаемость
Laser Technology for Structuring the Surface of Dental Titanium Implants. Part 2
V. P. Veiko1, Yu. Yu. Karlagina 1, V. V. Romanov 1,
R. M. Yatsuk 1, E. E. Egorova 1, Е. А. Zernitskaya 2,
А. I. Yaremenko 2, G. N. Chernenko 3, S. G. Gorny 4, G. V. Odintsova 1
ITMO University, Saint-Petersburg, Russia
Pavlov First Saint Petersburg State Medical University,
Saint-Petersburg, Russia
Lenmiriot Dental Implant Prosthetics Manufacture,
Saint-Petersburg, Russia
Laser Center LLS, Saint-Petersburg, Russia
The first part of this research deals with development of a method for the laser formation of a biocompatible surface morphology of titanium dental implants, providing a hydrophilic surface structure that has both micro- and nanorelief. In this second part of the study, we present the results of preclinical tests of the laser-induced relief’s biocompatibility. The implants with the modified surface showed an advanced proliferation of multipotent mesenchymal stromal cells over the entire surface area, even in open pores. Implants with such a surface also showed positive results of osseointegration in a living organism: three months after implantation, a new mature bone tissue is formed in the previously destroyed bone area, which is directly connected to the implant surface. The technology based on this method has been adopted into the production of a dental milling center for a full production cycle and a plant belonging to the ORTOS group of companies.
Keywords: Dental implants, implant success, laser surface treatment, preclinical studies, in vitro, in vivo, wall-to-wall production.
Received on: 04.06.2020
Accepted on: 24.06.2020
PRE-CLINICAL STUDIES OF BIOCOMPATIBILITY OF LASER-INDUCED SURFACE OF DENTAL IMPLANTS
In the first part of the research, two types of structures were formed by laser action on the surface of titanium dental implants: wells (“L” structure, laser power density 6.9 ∙ 107 W / cm2 in a two-pass processing mode) and grooves (“K” structure, power density 63 ∙ 107 W / cm2 in three-pass processing mode). Images of the implant surface before and after laser treatment, obtained by scanning electron microscopy, are shown in Fig. 1.
It is possible to assess qualitatively and quantitatively the viability of cells on foreign surfaces, i. e. structures obtained before (“P”) and after (“K” and “L”) laser treatment, possibly by conducting an in vitro study. We selected multipotent mesenchymal stromal cells (MMSC) as a model environment for the research, which, in turn, were isolated from human bone marrow. The cells, at the stage of cultivation, were stained with lentiviral particles carrying the gene of the fluorescent protein TurboFP635 (produced by Evrogen, Russia). The cells were transferred to the surface of the samples located in culture plates. The analysis of the results of cultivation was carried out 1, 5, 10, 15 and 20 days after the transfer of cells.
In the first control period, one day after planting the cells, the latter were found on all types of samples (Fig. 2). On the “P” structure, the cells were arranged in an even layer and had a fibroblast-like elongated shape, which indicated their normal adhesion. However, day after day, the initial number of viable cells on the surface of the “P” structure decreased and reached zero on the 20th day. The “L” structure in the first control period was covered with single cells of a rounded shape, characteristic of incomplete adhesion, however, on day 20 after the transfer of cells to the surface, the number of viable cells reached 196,000 cells per sample. This structure showed the largest number of cells in each control period, and by the end of the study reached 266,500 cells per sample, the maximum number among all samples. Based on the results of in vitro studies, it can be concluded that the optimal structure of those proposed for MSCs is the “K” structure.
After examining cell proliferation, cross-sections of the samples were taken to determine whether they were growing deep into the open pores of the structures or only lining the surface. The results obtained demonstrate that cells are located not only on the surface of structures, but also grow inside open pores. A qualitative analysis is shown in Figure 3.
The next stage of preclinical trial is in vivo study. For these purposes, 15 rabbits (male, 1.5 years old) were selected as a model environment. The animals were withdrawn from the experiment in two stages: after 1.5 months and after 3 months after implantation. The excised implants with already formed bone on them were dissected (Fig.4a), placed in formalin, degraded and fixed in methyl methacrylate. Then, a cut was made from each sample less than 50 μm thick (Fig. 4b). For histological examination, the specimens were stained using taluidione blue dye (Fig. 4b).
The analysis of the obtained sections was carried out by the method of optical microscopy (microscope Olympus BX 61). The images of all specimens (Fig. 5) show a lamellar bone with unevenly spaced Haversian canals, different in diameter. This indicates that there have been restructuring processes in the bone tissue. On all structures, cells of mature bone tissue (osteocytes) are found throughout the bone matrix; young fibrous tissue (colored in blue) and full-fledged mature bone tissue (colored in beige) are visible.
It was found that, in addition to the presence of mature bone tissue at the bone-implant interface and Haversian canals, which play an important role in tissue metabolism, osteocytes are located in the cavities of the “K” (Fig. 5b) and “L” (Fig. 5b) structures – mature bone cells.
Their predecessors, osteoblasts, in the process of forming new bone tissue, “considered” the grooves and wells as a suitable place for the formation of mature bone and, having turned into osteocytes, “walled up” in the cavities of the wells and grooves. Apparently, this behavior of osteoblasts is associated with the commensurability of the size of the cells themselves with the diameter of the wells and the width of the grooves, which correlates with our hypothesis about the optimal relief.
For a quantitative analysis of the data obtained, the BIC (Bone-to-implant contact) parameter was calculated, which characterizes the percentage of the implant border sections directly in contact with the mature bone tissue (Fig. 6). The highest value of the parameter according to the data obtained corresponds to the sample “K”.
In general, according to the results of in vivo studies, the “K” structure also demonstrated the best result of osseointegration.
PROSPECTS FOR THE INDUSTRY INTRODUCTION
Within the framework of this study, we have developed a method for laser formation of a biocompatible coating on the surface of titanium dental implants, which makes it possible to obtain a hydrophilic surface structure with a hierarchical micro- and nanorelief. The results of preclinical studies of the biocompatibility of a laser-induced surface on a dental implant are shown: it was confirmed that the proposed reliefs are not cytotoxic and provide a developed proliferation of multipotent msenchymal stromal cells over the entire surface area, even in open pores. The implants with the surface morphology under consideration showed positive results of osseointegration in a living organism: three months after implantation, a newly formed mature bone tissue is present in the previously destroyed area of the bone, and in the cavities of the wells and grooves of the “L” and “K” structures, as in the lacunae, located osteocytes.
Based on the results obtained for the St. Petersburg Dental Milling Center and the plant for the manufacture of orthopedic components for all known implant systems under the Lenmiriot brand (ORTOS group of companies), a technology for creating various types of dental implants has been developed, which is already at the stage of launching production. This manufacturer is the largest full-cycle dental milling center in Russia and has great potential to become the flagship of import substitution in this industry.
The following are the main technological stages performed in production when creating a dental implant:
then the implants undergo a laser surface structuring procedure, which consists of the following stages:
Thus, we have developed a full cycle of production of titanium dental implants with a laser-modified biocompatible coating, which has a great integration potential. The quality and novelty of this development are able to compete with foreign production and provide the market of our country with a high-tech product.
Although the presented results are complete, we believe that the possibilities of using laser technology to improve the quality of titanium implants are far from being exhausted. The search for optimal morphologies of the surface, the combination of hydrophilic and hydrophobic areas on it, along with the use of new materials, can ensure further sustainable progress in this area.
In vitro experiments and experimental protocols were approved by the Research Ethics Council of the Nizhny Novgorod State Medical Academy (Privolzhsky Research Medical University, Nizhny Novgorod) and comply with the principles of the Declaration of Helsinki.
Committee of the St. Petersburg State Medical University named after I. P. Pavlova carries out her activities in accordance with the Constitution of the Russian Federation, laws and other legal acts of the Russian Federation and St. Petersburg, the Declaration of Helsinki by the World Medical Association of 1964, amended in 1975, 1983, 1989, 1996, 2000 and 2013 years., international standards for clinical trials ICH Harmonized Tripartite Guideline for Good Clinical Practice (ICH GCP), industry standard OST 42–511–99 “Rules for conducting high-quality clinical trials in the Russian Federation”, which came into force on January 1, 1999., Recommendations of the Ethics Committees conducting the examination of WHO biomedical research, the Charter of Pavlov First Saint Petersburg State Medical University and the Regulations on the Ethics Committee of the Pavlov First Saint Petersburg State Medical University. The study “In vivo study of the integration processes of titanium dental implants with a laser-modified surface” was approved (excerpt from Minutes No. 208 of the meeting of the ethical committee of the Pavlov First Saint Petersburg State Medical University dated June 25, 2018).
The authors of the research express their gratitude to the research team of the Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University” of the Ministry of Health of the Russian Federation (Nizhny Novgorod), consisting of Daria Kuznetsova, Vadim Elagin and Elena Zagainova, for the study of cell biointegration on the laser-induced surface of VT6 titanium, and the staff of the Center for Shared Use of Scientific Equipment “Cellular and molecular technologies for the study of plants and fungi” of the Botanical Institute. V. L. Komarov RAS (St. Petersburg) Zernitsky A. Yu. and Zotov P. A. for carrying out histological and histomorphometric studies.
The reported study was supported by the Russian Science Foundation (project № 20-62-46045).
Contribution of authors
Problem statement and provision of resources: G. N. Chernenko, S. G. Mountain. Concept, study design and project management: V. P. Veiko, G. V. Odintsova. Text writing: Yu. Yu. Karlagin. Experiments on laser structuring of titanium surface: Yu. Yu. Karlagina, V. V. Romanov, R. M. Yatsuk. Concept of in vitro and in vivo studies: A. I. Yaremenko. Conducting and analyzing in vivo studies: E. A. Zernitskaya. Analysis of the results of in vitro and in vivo studies: Yu. Yu. Karlagina, E. E. Egorova.
ABOUT AUTHORS
V. P. Veiko (vadim.veiko@mail.ru), full professor, Doctor of Science (Technical), Head of the International Laboratory “Laser Micro-and Nanotechnologies”, Faculty of Laser Photonics and Optoelectronics, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0001-6071-3449
Yu. Yu. Karlagina (jujukarlagina@itmo.ru), engineer, International Laboratory “Laser Micro-and Nanotechnologies”, postgrad. student, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0002-6927-9551
V. V. Romanov (ionhcik@rambler.ru), engineer, postgrad. Student, faculty of laser photonics and optoelectronics, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0003-1468-9438
R. M. Yatsuk (yatsuk.roman@mail.ru), engineer, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0003-2502-7501
G. V. Odintsova (gvodintsova@itmo.ru), Cand. of Science (Technical), Research Associate, Laboratory “Laser Micro-and Nanotechnologies”, Faculty of Laser Photonics and Optoelectronics, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0001-9581-4290
E. E. Egorova (elena1998959@gmail.com), student, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0002-1461-0673
Е. А. Zernitskaya (zernitskaya_ekaterina@mail.ru), postgrad. Student, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russia.
ORCID: 0000-0002-3819-693X
А. I. Yaremenko (ayaremenko@me.com), Doctor of Medical Sciences, Professor, Head of the Department of Surgical Dentistry and Oral and Maxillofacial Surgery, Director of the Clinic for Oral and Maxillofacial Surgery, Vice-Rector for Academic Affairs, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russia.
ORCID: 0000-0002-7700-7724
G. N. Chernenko (office@ortos.biz), Director General, Lenmiriot Dental Implant Prosthetics Manufacture, Saint-Petersburg, Russia.
S. G. Gorny (info@newlaser.ru), Cand. of Science (Eng), “Laser Center”, Saint-Petersburg, Russia.
V. P. Veiko1, Yu. Yu. Karlagina 1, V. V. Romanov 1,
R. M. Yatsuk 1, E. E. Egorova 1, Е. А. Zernitskaya 2,
А. I. Yaremenko 2, G. N. Chernenko 3, S. G. Gorny 4, G. V. Odintsova 1
ITMO University, Saint-Petersburg, Russia
Pavlov First Saint Petersburg State Medical University,
Saint-Petersburg, Russia
Lenmiriot Dental Implant Prosthetics Manufacture,
Saint-Petersburg, Russia
Laser Center LLS, Saint-Petersburg, Russia
The first part of this research deals with development of a method for the laser formation of a biocompatible surface morphology of titanium dental implants, providing a hydrophilic surface structure that has both micro- and nanorelief. In this second part of the study, we present the results of preclinical tests of the laser-induced relief’s biocompatibility. The implants with the modified surface showed an advanced proliferation of multipotent mesenchymal stromal cells over the entire surface area, even in open pores. Implants with such a surface also showed positive results of osseointegration in a living organism: three months after implantation, a new mature bone tissue is formed in the previously destroyed bone area, which is directly connected to the implant surface. The technology based on this method has been adopted into the production of a dental milling center for a full production cycle and a plant belonging to the ORTOS group of companies.
Keywords: Dental implants, implant success, laser surface treatment, preclinical studies, in vitro, in vivo, wall-to-wall production.
Received on: 04.06.2020
Accepted on: 24.06.2020
PRE-CLINICAL STUDIES OF BIOCOMPATIBILITY OF LASER-INDUCED SURFACE OF DENTAL IMPLANTS
In the first part of the research, two types of structures were formed by laser action on the surface of titanium dental implants: wells (“L” structure, laser power density 6.9 ∙ 107 W / cm2 in a two-pass processing mode) and grooves (“K” structure, power density 63 ∙ 107 W / cm2 in three-pass processing mode). Images of the implant surface before and after laser treatment, obtained by scanning electron microscopy, are shown in Fig. 1.
It is possible to assess qualitatively and quantitatively the viability of cells on foreign surfaces, i. e. structures obtained before (“P”) and after (“K” and “L”) laser treatment, possibly by conducting an in vitro study. We selected multipotent mesenchymal stromal cells (MMSC) as a model environment for the research, which, in turn, were isolated from human bone marrow. The cells, at the stage of cultivation, were stained with lentiviral particles carrying the gene of the fluorescent protein TurboFP635 (produced by Evrogen, Russia). The cells were transferred to the surface of the samples located in culture plates. The analysis of the results of cultivation was carried out 1, 5, 10, 15 and 20 days after the transfer of cells.
In the first control period, one day after planting the cells, the latter were found on all types of samples (Fig. 2). On the “P” structure, the cells were arranged in an even layer and had a fibroblast-like elongated shape, which indicated their normal adhesion. However, day after day, the initial number of viable cells on the surface of the “P” structure decreased and reached zero on the 20th day. The “L” structure in the first control period was covered with single cells of a rounded shape, characteristic of incomplete adhesion, however, on day 20 after the transfer of cells to the surface, the number of viable cells reached 196,000 cells per sample. This structure showed the largest number of cells in each control period, and by the end of the study reached 266,500 cells per sample, the maximum number among all samples. Based on the results of in vitro studies, it can be concluded that the optimal structure of those proposed for MSCs is the “K” structure.
After examining cell proliferation, cross-sections of the samples were taken to determine whether they were growing deep into the open pores of the structures or only lining the surface. The results obtained demonstrate that cells are located not only on the surface of structures, but also grow inside open pores. A qualitative analysis is shown in Figure 3.
The next stage of preclinical trial is in vivo study. For these purposes, 15 rabbits (male, 1.5 years old) were selected as a model environment. The animals were withdrawn from the experiment in two stages: after 1.5 months and after 3 months after implantation. The excised implants with already formed bone on them were dissected (Fig.4a), placed in formalin, degraded and fixed in methyl methacrylate. Then, a cut was made from each sample less than 50 μm thick (Fig. 4b). For histological examination, the specimens were stained using taluidione blue dye (Fig. 4b).
The analysis of the obtained sections was carried out by the method of optical microscopy (microscope Olympus BX 61). The images of all specimens (Fig. 5) show a lamellar bone with unevenly spaced Haversian canals, different in diameter. This indicates that there have been restructuring processes in the bone tissue. On all structures, cells of mature bone tissue (osteocytes) are found throughout the bone matrix; young fibrous tissue (colored in blue) and full-fledged mature bone tissue (colored in beige) are visible.
It was found that, in addition to the presence of mature bone tissue at the bone-implant interface and Haversian canals, which play an important role in tissue metabolism, osteocytes are located in the cavities of the “K” (Fig. 5b) and “L” (Fig. 5b) structures – mature bone cells.
Their predecessors, osteoblasts, in the process of forming new bone tissue, “considered” the grooves and wells as a suitable place for the formation of mature bone and, having turned into osteocytes, “walled up” in the cavities of the wells and grooves. Apparently, this behavior of osteoblasts is associated with the commensurability of the size of the cells themselves with the diameter of the wells and the width of the grooves, which correlates with our hypothesis about the optimal relief.
For a quantitative analysis of the data obtained, the BIC (Bone-to-implant contact) parameter was calculated, which characterizes the percentage of the implant border sections directly in contact with the mature bone tissue (Fig. 6). The highest value of the parameter according to the data obtained corresponds to the sample “K”.
In general, according to the results of in vivo studies, the “K” structure also demonstrated the best result of osseointegration.
PROSPECTS FOR THE INDUSTRY INTRODUCTION
Within the framework of this study, we have developed a method for laser formation of a biocompatible coating on the surface of titanium dental implants, which makes it possible to obtain a hydrophilic surface structure with a hierarchical micro- and nanorelief. The results of preclinical studies of the biocompatibility of a laser-induced surface on a dental implant are shown: it was confirmed that the proposed reliefs are not cytotoxic and provide a developed proliferation of multipotent msenchymal stromal cells over the entire surface area, even in open pores. The implants with the surface morphology under consideration showed positive results of osseointegration in a living organism: three months after implantation, a newly formed mature bone tissue is present in the previously destroyed area of the bone, and in the cavities of the wells and grooves of the “L” and “K” structures, as in the lacunae, located osteocytes.
Based on the results obtained for the St. Petersburg Dental Milling Center and the plant for the manufacture of orthopedic components for all known implant systems under the Lenmiriot brand (ORTOS group of companies), a technology for creating various types of dental implants has been developed, which is already at the stage of launching production. This manufacturer is the largest full-cycle dental milling center in Russia and has great potential to become the flagship of import substitution in this industry.
The following are the main technological stages performed in production when creating a dental implant:
- implants are milled from a long titanium rod on a milling machine;
- after grinding, the implants go through a stage of cleaning from residues of milling oils and other contaminants;
- then the implants are sent for tumbling to clean the edges from burrs;
- then the implants are cleaned in an ultrasonic bath with a special detergent;
- after which the implants pass the quality control department;
- then, they are sent again for cleaning in an ultrasonic bath, packed in special kraft bags and sterilized;
- after that, in a “laminar flow hood” in a sterile environment, the implants are installed on the rigs for further operations;
then the implants undergo a laser surface structuring procedure, which consists of the following stages:
- the implant is installed on a special rotary mechanism in the working area of the laser machine;
- further, the rotary mechanism tilts the implant at a certain angle to process the lateral surface of the implant thread, on one side and on the other;
- further the cylindrical surface of the implant itself is processed (the area at the top of the thread and between the teeth);
- the surface of the cutouts is then processed, if any;
- the end of the implant is processed at the last stage;
- after processing on a laser machine, the implants undergo quality control of the created structure on an optical microscope with high magnification;
- after which the implants are again cleaned in an ultrasound bath, sterilized and packaged.
- further in a “laminar flow cabinet” in a sterile environment, the implants are packed in blisters (final packaging for storage and sale);
- after the implants in packages are re-sterilized (irradiated with gamma radiation);
sent to the warehouse / sale.
Thus, we have developed a full cycle of production of titanium dental implants with a laser-modified biocompatible coating, which has a great integration potential. The quality and novelty of this development are able to compete with foreign production and provide the market of our country with a high-tech product.
Although the presented results are complete, we believe that the possibilities of using laser technology to improve the quality of titanium implants are far from being exhausted. The search for optimal morphologies of the surface, the combination of hydrophilic and hydrophobic areas on it, along with the use of new materials, can ensure further sustainable progress in this area.
In vitro experiments and experimental protocols were approved by the Research Ethics Council of the Nizhny Novgorod State Medical Academy (Privolzhsky Research Medical University, Nizhny Novgorod) and comply with the principles of the Declaration of Helsinki.
Committee of the St. Petersburg State Medical University named after I. P. Pavlova carries out her activities in accordance with the Constitution of the Russian Federation, laws and other legal acts of the Russian Federation and St. Petersburg, the Declaration of Helsinki by the World Medical Association of 1964, amended in 1975, 1983, 1989, 1996, 2000 and 2013 years., international standards for clinical trials ICH Harmonized Tripartite Guideline for Good Clinical Practice (ICH GCP), industry standard OST 42–511–99 “Rules for conducting high-quality clinical trials in the Russian Federation”, which came into force on January 1, 1999., Recommendations of the Ethics Committees conducting the examination of WHO biomedical research, the Charter of Pavlov First Saint Petersburg State Medical University and the Regulations on the Ethics Committee of the Pavlov First Saint Petersburg State Medical University. The study “In vivo study of the integration processes of titanium dental implants with a laser-modified surface” was approved (excerpt from Minutes No. 208 of the meeting of the ethical committee of the Pavlov First Saint Petersburg State Medical University dated June 25, 2018).
The authors of the research express their gratitude to the research team of the Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University” of the Ministry of Health of the Russian Federation (Nizhny Novgorod), consisting of Daria Kuznetsova, Vadim Elagin and Elena Zagainova, for the study of cell biointegration on the laser-induced surface of VT6 titanium, and the staff of the Center for Shared Use of Scientific Equipment “Cellular and molecular technologies for the study of plants and fungi” of the Botanical Institute. V. L. Komarov RAS (St. Petersburg) Zernitsky A. Yu. and Zotov P. A. for carrying out histological and histomorphometric studies.
The reported study was supported by the Russian Science Foundation (project № 20-62-46045).
Contribution of authors
Problem statement and provision of resources: G. N. Chernenko, S. G. Mountain. Concept, study design and project management: V. P. Veiko, G. V. Odintsova. Text writing: Yu. Yu. Karlagin. Experiments on laser structuring of titanium surface: Yu. Yu. Karlagina, V. V. Romanov, R. M. Yatsuk. Concept of in vitro and in vivo studies: A. I. Yaremenko. Conducting and analyzing in vivo studies: E. A. Zernitskaya. Analysis of the results of in vitro and in vivo studies: Yu. Yu. Karlagina, E. E. Egorova.
ABOUT AUTHORS
V. P. Veiko (vadim.veiko@mail.ru), full professor, Doctor of Science (Technical), Head of the International Laboratory “Laser Micro-and Nanotechnologies”, Faculty of Laser Photonics and Optoelectronics, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0001-6071-3449
Yu. Yu. Karlagina (jujukarlagina@itmo.ru), engineer, International Laboratory “Laser Micro-and Nanotechnologies”, postgrad. student, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0002-6927-9551
V. V. Romanov (ionhcik@rambler.ru), engineer, postgrad. Student, faculty of laser photonics and optoelectronics, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0003-1468-9438
R. M. Yatsuk (yatsuk.roman@mail.ru), engineer, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0003-2502-7501
G. V. Odintsova (gvodintsova@itmo.ru), Cand. of Science (Technical), Research Associate, Laboratory “Laser Micro-and Nanotechnologies”, Faculty of Laser Photonics and Optoelectronics, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0001-9581-4290
E. E. Egorova (elena1998959@gmail.com), student, ITMO University, Saint-Petersburg, Russia.
ORCID: 0000-0002-1461-0673
Е. А. Zernitskaya (zernitskaya_ekaterina@mail.ru), postgrad. Student, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russia.
ORCID: 0000-0002-3819-693X
А. I. Yaremenko (ayaremenko@me.com), Doctor of Medical Sciences, Professor, Head of the Department of Surgical Dentistry and Oral and Maxillofacial Surgery, Director of the Clinic for Oral and Maxillofacial Surgery, Vice-Rector for Academic Affairs, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russia.
ORCID: 0000-0002-7700-7724
G. N. Chernenko (office@ortos.biz), Director General, Lenmiriot Dental Implant Prosthetics Manufacture, Saint-Petersburg, Russia.
S. G. Gorny (info@newlaser.ru), Cand. of Science (Eng), “Laser Center”, Saint-Petersburg, Russia.
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