Ekstrakte Edilemeyen Tıbbi Cihazların Sitotoksisite ve İrritasyon Potansiyellerinin Alternatif Doku Modelleri ile Araştırılması

Abstract

Biocompatibility assessment is a critical step in ensuring the safe placement of medical devices on the market. Cytotoxicity, irritation, and sensitization are among the fundamental biological risks that must be evaluated for all medical devices. Animal testing, which has long been widely used for the assessment of these risks, is increasingly being replaced by alternative in vitro methods due to ethical concerns, high costs, time requirements, and issues related to standardization. The limited availability of data on the in vitro evaluation of medical devices in liquid, gel, particulate, and cream forms—which are particularly difficult or impossible to extract—makes research in this area particularly important. In this thesis, the cytotoxicity and irritation potential of non-extractable medical device samples belonging to different risk classes were evaluated using alternative in vitro methods. Cytotoxicity assessments were performed using the MTT assay in 3T3 cell cultures, while irritation potential was evaluated using a Reconstructed Human Epidermis (RhE) model in accordance with OECD Test Guideline 439. In addition, TNF-α, IL-2, IL-4, IL-6, and IL-8 levels were analyzed in RhE tissue culture media by ELISA to provide a more comprehensive evaluation of the irritation response. The cytotoxicity studies demonstrated concentration-dependent cellular responses to the tested medical device samples. While some samples exhibited cytotoxic effects at higher concentrations, they significantly increased cell viability at lower concentrations. Irritation testing using the RhE model revealed that none of the investigated medical devices were classified as irritants. Cytokine analyses showed that TNF-α, IL-2, IL-4, IL-6, and IL-8 levels were significantly elevated compared with the negative control group, while remaining lower than those observed in the positive control group. The findings indicate that cell culture systems and three-dimensional human epidermis models represent applicable and reliable alternative approaches for the biocompatibility assessment of non-extractable medical devices without the need for extraction procedures. Furthermore, cytokine analysis was shown to provide additional information beyond conventional cell viability measurements, enabling a more comprehensive characterization of biological responses induced by medical device materials. Overall, this study contributes to the scientific literature by providing data supporting the use of alternative in vitro approaches in the biocompatibility evaluation of non-extractable medical devices.