ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2026-2-101-114ssmu-6538Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSМетаболическая реакция клеток на изменение физико-химического состояния поверхности никелида титана, индуцированное ультрафиолетовым лазерным излучением с длиной волны 266 нмMetabolic reaction of cells to changes in the physical and chemical state of the nitinol surface induced by ultraviolet laser radiation with a wavelength of 266 nmhttps://orcid.org/0000-0003-3465-8452ХлусовИ. А.KhlusovI. A.

Хлусов Игорь Альбертович – д-р мед. наук, профессор кафедры морфологии и общей патологии, зав. лабораторией клеточных и  микрофлюидных технологий; ст. науч. сотрудник

Россия, 634050, г. Томск, Московский тракт, 2

Россия, 634055, г. Томск, пр. Академический, 2/3

2 Moskovsky trakt, 634050 Tomsk, Russian Federation

2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation

khlusov63@mail.ruhttps://orcid.org/0000-0003-3690-0177КокоревО. В.KokorevO. V.

Кокорев Олег Викторович – д-р мед. наук, профессор кафедры биохимии и молекулярной  биологии с курсом клинической лабораторной диагностики

Россия, 634050, г. Томск, Московский тракт, 2

2 Moskovsky trakt, 634050 Tomsk, Russian Federation

https://orcid.org/0000-0001-8401-7181ГороховаА. В.GorokhovaA. V.

Горохова Анна Владимировна – лаборант-исследователь, кафедра морфологии и общей патологии; инженер

Россия, 634050, г. Томск, Московский тракт, 2

Россия, 634055, г. Томск, пр. Академический, 2/3

2 Moskovsky trakt, 634050 Tomsk, Russian Federation 

2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation 

a.gorokhova3062@gmail.comhttps://orcid.org/0000-0002-8056-3967НасибовТ. Ф.NasibovT. F.

Насибов Темур Фиррудин оглы – лаборант-исследователь, кафедра морфологии и общей патологии; инженер 

Россия, 634050, г. Томск, Московский тракт, 2

Россия, 634055, г. Томск, пр. Академический, 2/3

2 Moskovsky trakt, 634050 Tomsk, Russian Federation 

2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation

temur.nsbv@gmail.comhttps://orcid.org/0000-0001-5505-7141КривощековС. В.KrivoshchekovS. V.

Кривощеков Сергей Владимирович – канд. хим. наук, доцент кафедры фармацевтического анализа

Россия, 634050, г. Томск, Московский тракт, 2

 2 Moskovsky trakt, 634050 Tomsk, Russian Federation 

krivoshchekov.sv@ssmu.ruhttps://orcid.org/0000-0002-1980-3941ЧебодаеваВ. В.ChebodaevaV. V.

Чебодаева Валентина Вадимовна – канд. тех. наук, науч. cотрудник; мл. науч. сотрудник

Россия, 634055, г. Томск, пр. Академический, 2/3 

Россия, 634055, г. Томск, пр. Академический, 2/4

2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation

2/4 Akademichesky Ave., 634055 Tomsk, Russian Federation

vtina5@mail.ruhttps://orcid.org/0000-0002-4779-9820БразовскийК. С.BrazovskyK. S.

Бразовский Константин Станиславович – д-р тех. наук, профессор кафедры медицинской и биологической кибернетики

Россия, 634050, г. Томск, Московский тракт, 2

 2 Moskovsky trakt, 634050 Tomsk, Russian Federation 

brazovsky.ks@ssmu.ruhttps://orcid.org/0000-0001-9583-5358ХлусоваМ. Ю.KhlusovaM. Yu.

Хлусова Марина Юрьевна – канд. мед. наук, доцент кафедры патофизиологии

Россия, 634050, г. Томск, Московский тракт, 2

2 Moskovsky trakt, 634050 Tomsk, Russian Federation

hlusova.my@ssmu.ruhttps://orcid.org/0000-0002-5941-5732СаблинаТ. Ю.SablinaT. Yu.

Саблина Татьяна Юрьевна – канд. тех. наук, науч. сотрудник, лаборатория газовых лазеров

Россия, 634055, г. Томск, пр. Академический, 2/3

 2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation 

sty@lgl.hcei.tsc.ruhttps://orcid.org/0000-0003-0236-2227КандауроваМ. Ю.KandaurovaM. Yu.

Кандаурова Марина Юрьевна – канд. физ.-мат. наук, науч. сотрудник, лаборатория газовых лазеров

Россия, 634055, г. Томск, пр. Академический, 2/3

2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation

panchenko.marina4@gmail.comhttps://orcid.org/0000-0003-3219-9299ЗятиковИ. А.ZyatikovI. A.

Зятиков Илья Александрович – мл. науч. сотрудник, лаборатория газовых лазеров

Россия, 634055, г. Томск, пр. Академический, 2/3

 2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation 

zyatikov@lgl.hcei.tsc.ruhttps://orcid.org/0000-0001-8017-7268ПанченкоЮ. Н.PanchenkoYu. N.

Панченко Юрий Николаевич – д-р физ.-мат. наук, гл. науч. сотрудник, зав. лабораторией газовых лазеров

Россия, 634055, г. Томск, пр. Академический, 2/3

2/3 Akademichesky Ave., 634055 Tomsk, Russian Federation

yu.n.panchenko@mail.ruСибирский государственный медицинский университет (СибГМУ); Институт сильноточной электроники Сибирского отделения Российской академии наук (ИСЭ СО РАН)РоссияSiberian State Medical University; Institute of High Current Electronics, Siberian Branch of the Russian Academy of Sciences (IHCE SB RAS)Russian FederationСибирский государственный медицинский университет (СибГМУ)РоссияSiberian State Medical UniversityRussian FederationИнститут сильноточной электроники Сибирского отделения Российской академии наук (ИСЭ СО РАН); Институт физики прочности и материаловедения Сибирского отделения Российской академии наук (ИФПМ СО РАН)РоссияInstitute of High Current Electronics, Siberian Branch of the Russian Academy of Sciences (IHCE SB RAS); Institute of Strength Physics and Materials Science, Siberian Branch of the Russian Academy of Sciences (ISPMS SB RAS)Russian FederationИнститут сильноточной электроники Сибирского отделения Российской академии наук (ИСЭ СО РАН)РоссияInstitute of High Current Electronics, Siberian Branch of the Russian Academy of Sciences (IHCE SB RAS)Russian Federation202623072026252101114Copyright © Хлусов И.А., Кокорев О.В., Горохова А.В., Насибов Т.Ф., Кривощеков С.В., Чебодаева В.В., Бразовский К.С., Хлусова М.Ю., Саблина Т.Ю., Кандаурова М.Ю., Зятиков И.А., Панченко Ю.Н., 20262026Хлусов И.А., Кокорев О.В., Горохова А.В., Насибов Т.Ф., Кривощеков С.В., Чебодаева В.В., Бразовский К.С., Хлусова М.Ю., Саблина Т.Ю., Кандаурова М.Ю., Зятиков И.А., Панченко Ю.Н.Khlusov I.A., Kokorev O.V., Gorokhova A.V., Nasibov T.F., Krivoshchekov S.V., Chebodaeva V.V., Brazovsky K.S., Khlusova M.Y., Sablina T.Y., Kandaurova M.Y., Zyatikov I.A., Panchenko Y.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/6538

Цель: оценка с помощью 3-[4,5-диметилтиазол-2-ил]-2,5-дифенилтетразолия бромида (МТТ) клеточной реакции in vitro на изменение физико-химического состояния (дзета-потенциала, смачиваемости, топографии) поверхности сплава на основе никелида титана (нитинола) после обработки ультрафиолетовым лазерным излучением (УФ-ЛИ) с длиной волны 266 нм.Материалы и методы. Клеточную культуру MCF-7 инкубировали в течение 24 ч с пластинами из сплава на основе никелида титана, до и после обработки УФ-ЛИ (плотность энергии 0,1 Дж/см2). На образцах измеряли индекс шероховатости Ra (ГОСТ 2789-73) и контактный угол смачивания поверхности водой. Дзета-потенциалы поверхности подложек из нитинола и MCF-7 клеток определяли с использованием анализаторов для плоских образцов (SurPASS 3) и частиц (Litesizer DLS 500) соответственно. Метаболическую активность клеточной культуры определяли с помощью МТТ-теста, рекомендуемого ГОСТ ISO 10993-5-2023 для оценки in vitro цитотоксичности медицинских материалов и изделий. Биоинформатический in silico анализ внутриклеточных сигнальных и метаболических путей осуществляли в базе данных Wiki Pathways.Результаты. Модификация поверхности УФ-ЛИ статистически значимо снижала токсический отклик (падение метаболической активности) MCF-7 клеток на контакт с подложкой из нитинола. Обработка УФЛИ не влияла на величину дзета-потенциала, но существенно уменьшала контактный угол смачивания водой (с 75 до 8,7°), а также повышала Ra поверхности образцов (с 71,5 до 93,9 нм). Анализ in silico с позиций механотрансдукции показал, что шероховатость и гидрофильность (гидрофобность) нитинола могут индуцировать экспрессию генов в MCF-7 клетках независимо друг от друга, а также через перекрестные молекулярные механизмы. При этом некоторые сигнальные пути (WP5504, WP3680, WP5477, WP3941, WP5046, WP2435) близки к системам, участвующим в редукции МТТ-реагента как маркера программы клеточной смерти, индуцированной метаболическим дисбалансом MCF-7 клеток.Заключение. Обработка УФ-ЛИ способствует увеличению гидрофильности и (или) наношероховатости, но не дзета-потенциала поверхности подложек из нитинола. Это может инициировать каскад молекулярных механизмов, регулирующих клеточно-тканевые реакции на имплантируемые материалы, включая индукцию воспаления, активацию гемостаза, ангиоспазм и регенерацию кровеносного русла, а также метаболическую активность клеток-мишеней.

Aim. MTT (methylthiazolyldiphenyl-tetrazolium bromide) viability assessment of the in vitro cellular response to changes in the physicochemical properties (zeta potential, wettability, topography) of the nitinol surface after treatment with ultraviolet (UV) laser radiation (UV-LR) with a wavelength of 266 nm.Materials and methods. The MCF-7 cell culture was incubated with nitinol-based alloy plates for 24 hours, before and after exposure to UV light (wavelength 266 nm, energy density 0.1 J/cm²) with a Q-smart 850 pulsed Nd:YAG laser. The samples were then analyzed for roughness (Ra) (GOST 2789-73) and surface contact angle with water. Zeta (ζ) potentials were also measured for both nitinol-based alloy substrates (SurPASS 3) and MCF-7 cells (Litesizer DLS 500). Metabolic activity of the cells was assessed using the MTT test, as recommended by GOST ISO 10993-5-2023 for the in vitro assessment of the cytotoxicity of medical materials and devices. Bioinformatics in silico analysis of intracellular signaling and metabolic pathways was conducted using the WikiPathways database.Results. Surface modification caused by UV-LR significantly reduced the toxic response (decrease in metabolic activity) of MCF-7 cells to the nitinol-based alloy substrate. UV-LR did not affect the zeta potential (±10 mV from the isoelectric point), but it significantly decreased the water contact angle (from 75 to 8.7°) and increased the Ra index of surface roughness (from 71.5 nm to 93.9 nm). In silico mechanotransduction analysis revealed that the roughness and hydrophilicity/hydrophobicity of nitinol can independently induce gene expression in MCF-7 cells, as well as through cross-talking molecular mechanisms. At the same time, several signaling pathways (WP5504, WP3680, WP5477, WP3941, WP5046, and WP2435) were found to be close to those involved in the reduction of the MTT reagent, which is used as a marker for the cell death program induced by metabolic imbalance in MCF-7 cells. Conclusion. UV-LR promotes an increase in hydrophilicity and/or nanoroughness of the nitinol-based alloy surface, but it does not affect the zeta potential. This may initiate a cascade of molecular mechanisms regulating cellular and tissue responses to implanted materials. These events can include inflammation, hemostasis activation, angiospasm, vessel regeneration, and metabolic activity of target cells.

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The authors declare that there are no conflicts of interest present.