P17-02 Towards animal-free immunotoxicology testing: macrophage-centered in vitro assessment of foreign body reaction

Foreign body reaction (FBR), leading to chronic inflammation and fibrotic encapsulation of implants, poses a challenge in the development of implantable medical devices. Immunomodulatory coatings and materials have been extensively researched to mitigate FBR and its consequences. Currently, in vivo a nimal studies according to ISO/DIS 10993-6:2024 are the gold standard for preclinical risk assessment of medical devices and the prediction of the FBR, while immunotoxicology testing considerations of ISO/TS 10993-20:2006 remain in state of technical specification. However, ethical concerns regarding animal studies and the lack of specific and standardized in vitro alternatives for the FBR prediction necessitate the consideration of new approaches. Due to their central role in the outcome of FBR, macrophages are highly studied and represent the key in the development of promising in vitro test strategies. In this project, we propose a novel testing strategy to assess the degree of induction of FBR in vitro. Our approach is based on the quantitative analysis of THP-1 derived macrophage responses in direct contact to the medical device specimen surface. The main objectives of this study are to define key events related to macrophages in the FBR, establish suitable in vitro test scenarios for the key events, and specify relevant analytical markers for characterizing the FBR along this Adverse Outcome Pathway. This concept finds application not only in early-stage assessment of improved implant coatings and materials for various implantable medical devices but has the potential to contribute to the development of next-generation biocompatibility evaluation standards derived from hypothesis-driven risk assessment approaches.