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Foreign body reaction: towards a macrophage-centered adverse outcome pathway for fibrotic encapsulation
Tom Meseberg1, Susanne Kurz1, Juliane Spohn1
1Bio- and Nanotechnology Department, Fraunhofer Institute for Ceramic Technologies and Systems (FHG), Dresden, Germany.
Abstract:
The foreign body reaction (FBR), characterized by chronic inflammation and fibrotic capsule formation around implanted medical devices, remains a major cause in device-related complications. Current preclinical risk assessment relies on in vivo testing according to ISO 10993-6:2024, which are limited by species differences, incomplete mechanistic insight, and ethical concerns. Additionally, ISO/TS 10993-20:2006 outlines immunotoxicity knowledge regarding implant-induced effects such as FBR and specifies a collection of in vitro assays. The perspective presented here, aims to explore the applicability of the Adverse Outcome Pathway (AOP) framework to FBR in order to integrate evidence and methods into a structured mechanistic context and facilitate the application of in vitro tests in preclinical risk assessment of FBR. A targeted literature review was conducted to identify and organize biological mechanisms into a putative AOP, map available new approach methodologies, and highlight critical knowledge gaps and uncertainties. This initial framework may guide early screening for low-FBR materials and support mechanistically anchored, non-animal biocompatibility assessment strategies for medical devices.
Insights
The Adverse Outcome Pathway (AOP) framework can structure knowledge on foreign body reactions (FBR) to medical devices. This approach supports developing non-animal biocompatibility testing strategies for improved preclinical risk assessment.
Area of Science:
- Biomaterials Science
- Toxicology
- Immunology
Background:
- Foreign body reaction (FBR) causes medical device complications through inflammation and fibrosis.
- Current in vivo testing (ISO 10993-6:2024) has limitations including species variability and ethical concerns.
- Existing immunotoxicity guidelines (ISO/TS 10993-20:2006) suggest in vitro assays for implant-induced effects.
Purpose of the Study:
- To explore the Adverse Outcome Pathway (AOP) framework's applicability to FBR.
- To integrate evidence and methods into a structured mechanistic context for FBR assessment.
- To facilitate the use of in vitro tests in preclinical risk assessment of FBR.
Main Methods:
- Conducted a targeted literature review to identify biological mechanisms of FBR.
- Organized identified mechanisms into a putative AOP framework.
- Mapped available new approach methodologies (NAMs) relevant to FBR.
Main Results:
- An initial AOP framework for FBR was developed.
- Available NAMs were identified and mapped within the AOP context.
- Critical knowledge gaps and uncertainties in FBR assessment were highlighted.
Conclusions:
- The AOP framework offers a structured approach to understanding FBR.
- This framework can guide early screening for materials with low FBR potential.
- It supports the development of mechanistically anchored, non-animal biocompatibility assessment strategies for medical devices.
