Beyond Encapsulation: Exploring Macrophage-Fibroblast Cross Talk in Implant-Induced Fibrosis

testing and predictive modeling. However, the development of an AOP for the FBR does require a comprehensive understanding of the molecular initiating events and key event relationships to identify which events are essential. In this article, we describe the current knowledge on macrophage-fibroblast cross talk in the FBR and discuss how targeted research can help build an AOP for implant-related fibrosis. Impact statement Biomaterials are widely used to manufacture medical devices, but implantation is associated with a foreign body response (FBR), which may lead to failure of the implants. Surface properties are related to FBR severity. In this review, we zoom in on the cross talk between the two key players, macrophages and fibroblasts, and propose the use of Adverse Outcome Pathways to decipher the causal link between material properties and the severity of the FBR. This approach will help increase a mechanistic understanding of the FBR and, thus, aid in the design of immunomodulatory implant surfaces.