Toxic effects of medical devices in in vitro and in vivo test models

Introduction. During the development of methodological approaches to accelerated shelf life determination for new medical devices, it is important to determine the toxic properties of devices after their stay in specially created conditions of aggravated aging at elevated temperatures using laboratory animals and alternative test models.

Material and methods. To assess the toxicity of medical devices after accelerated aging, we selected disposable sterile devices subjected to single short-term, long-term, or continuous contact with the internal environment of patients, and both domestically and internationally manufactured non-sterile devices subjected to short-term contact with the patient’s body surface. Aggravated aging conditions were simulated by thermostating the devices. The experimental samples were aged at temperature of plus 80–95 °C for 3.7, 11.2, and 18.7 days. After thermostating, clinical conditions were simulated, for which extracts were prepared from each medical device. The toxic properties of the extracts were subsequently assessed in in vitro and in vivo test models, including sensitizing and pyrogenic effects, hemocompatibility, and cytotoxicity.

Results. All studied medical devices, with varying durations and method of contact with patients, did not exhibit sensitizing effects in the mouse paw swelling test model and complied with hygiene standards after aging under aggravated conditions. Cell death of primary embryonic fibroblast cultures in the in vitro test model was observed after the addition of extracts from the devices, as well as changes in the pyrogenic properties of the devices and a decrease in their compatibility with blood.

Limitations. Are related to in vitro and in vivo test models used to assess the toxic properties of devices after accelerated aging, as well as the medical devices used in the experiments.

Conclusion. The toxic effects of medical devices with varying durations and method of contact with patients depended on the aging time under aggravated conditions. The highest toxic effects were demonstrated by medical devices with short-term contact with the patient’s body surface, while the lowest were demonstrated by devices with prolonged or continuous contact with the patient’s internal environment. The most sensitive test model for studying the biological effects of medical devices under accelerated aging conditions was the primary culture of embryonic fibroblasts from white rats. To establish the shelf life of new medical devices, it is necessary to study their toxic properties after modeling accelerated aging.

Compliance with ethical standards. A positive conclusion was received from the Bioethics Committee of the Research Institute of Hygiene, Toxicology, Epidemiology, Virology, and Microbiology of the Republican Center for Hygiene, Epidemiology, and Public Health (Protocol No. 4 of August 22, 2023). The study was conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123) and with the Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contributions:
Hrynchak V.A. – study concept and design, material processing, editing;
Protasevich U.S. – data collection and processing, writing, statistical analysis, editing.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interest. The authors declare no obvious or potential conflicts of interest in connection with the publication of this article.

Funding. The evaluation was conducted as part of the “Human Environment Safety” subprogram of the State Scientific and Technical Program “Scientific and Technical Support for the Quality and Availability of Medical Services” – Task 02.15. “Develop and implement a method for determining the expiration dates of single-use medical devices” (state registration number 2023166).

Received: December 19, 2025 / Revised: January 26, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

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