Study of biocompatibility and antitumor cytotoxic activity in vitro of Zn – 1 %Mg and Zn – 1 %Mg – 0.1 %Ca alloys strengthened by equal angular pressing

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Abstract

Introduction. The biological activity of potential biodegradable zinc-based alloys that are promising for oncoorthopedics was studied in this work. The alloys were processed by equal-channel angular pressing, which made it possible to increase their strength due to microstructure refinement and the ability to provide the functionality of osteosynthesis, fixed due to the metal structure developed on their basis.

Aim. Investigation of effect of equal-channel angular pressing (ECAP) treatment on strength, ductility, degradation rate, biocompatibility in vitro and cytotoxicity against SKOV-3 tumor cells of the Zn – 1 %Mg and Zn – 1 %Mg – 0.1 %Ca alloys.

Materials and methods. The Zn – 1 %Mg and Zn – 1 %Mg – 0.1 %Ca alloys in the initial state and after ECAP were used as objects of study, and blood cells of CBA mice were used as model systems. To assess the hemolytic activity, the samples were incubated with red blood cells for 4 and 24 hours at 37 °C, assessing the relative increase in the level of extracellular hemoglobin compared to the intact control. The cytotoxicity of the alloys was assessed by the change in the level of extracellular lactate dehydrogenase (LDH) activity after 24 hours of incubation with mononuclear white blood cells. The study of antitumor cytotoxic activity was carried out on human ovarian cancer cells of the SKOV-3 line in vitro, assessing their survival after 48 hours of incubation with alloy samples using the LDH test.

Results. As a result of the studies, it was concluded that the studied alloys after ECAP treatment retained their biocompatibility, since there were no signs of hemolysis and cytotoxicity with respect to blood cells. However, contact with samples of all studied alloys in vitro induced a significant inhibition of the metabolic activity of the ovarian cancer cell culture in comparison with the control. Incubation with alloys samples leads to a decrease in cellular activity by an average of 49 % and 59 % for Zn – 1 %Mg and Zn – 1 %Mg – 0.1 %Ca alloys, respectively. The addition of calcium to the composition of the alloy Zn – 1 %Mg contributed to the growth of antitumor cytotoxic activity.

Conclusion. Thus, based on the results of assessing the hemolytic activity and cytotoxicity of the samples, we can conclude that the studied alloys are biocompatible. It was also found that Zn – 1 %Mg and Zn – 1 %Mg – 0.1 %Ca alloys had a pronounced cytotoxic effect on SKOV-3 tumor cells. The obtained data indicate the prospects for the development of a new type of medical devices based on the studied alloys, promising, in particular, for oncoorthopedics: a metal structure developed on their basis can ensure the strength of osteosynthesis, reduce the risk of local recurrence of oncological disease and does not require a second operation to remove the device.

About the authors

N. S. Martynenko

A.A. Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences

Author for correspondence.
Email: nataliasmartynenko@gmail.com
ORCID iD: 0000-0003-1662-1904

49 Leninskiy Prospect, Moscow 119334

Russian Federation

N. Yu. Anisimova

A.A. Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences; N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; National University of Science and Technology “MISIS”

ORCID iD: 0000-0002-4370-6578

49 Leninskiy Prospect, Moscow 119334

24 Kashirskoe Shosse, Moscow 115522

4 Leninskiy Prospect, Moscow 119049

Russian Federation

O. V. Rybalchenko

A.A. Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences

ORCID iD: 0000-0002-0403-0800

49 Leninskiy Prospect, Moscow 119334

Russian Federation

M. V. Shinkareva

National University of Science and Technology “MISIS”

ORCID iD: 0000-0002-8208-9111

4 Leninskiy Prospect, Moscow 119049

Russian Federation

D. R. Temralieva

A.A. Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences

ORCID iD: 0000-0002-8392-7826

49 Leninskiy Prospect, Moscow 119334

Russian Federation

K. M. Novruzov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-0773-255X

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

A. G. Raab

Ufa University of Science and Technology

ORCID iD: 0000-0003-1993-413X

32 Zaki Validi St., Ufa 450076

Russian Federation

E. A. Lukyanova

A.A. Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences

ORCID iD: 0000-0001-7122-6427

49 Leninskiy Prospect, Moscow 119334

Russian Federation

E. A. Kornyushenkov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0002-3903-8773

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

D. V. Filonenko

General Oncology Department of the A. S. Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

ORCID iD: 0000-0002-9943-3054

86 Entuziastov Shosse, Moscow 111123

Russian Federation

D. E. Mitrushkin

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

ORCID iD: 0000-0003-3778-303X

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

S. V. Dobatkin

A.A. Baikov Institute of Metallurgy and Materials Science of the Russian Academy of Sciences

ORCID iD: 0000-0003-4232-927X

49 Leninskiy Prospect, Moscow 119334

Russian Federation

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