Abstract
Interactions between biological tissues and implantable biomaterials such as surgical sutures lead to a Foreign Body Response (FBR), which can result in fibrotic encapsulation, scarring and biomaterial rejection. To investigate the cell and tissue signalling events that underlie development of an FBR, we use live imaging of transgenic zebrafish reporter lines to observe how inflammation and angiogenesis differ between a healthy acute wound and an FBR. We see an expanding zone of inflammation extending back from suture margins; this correlates to an avascular zone, and subsequently to a defined fibrotic encapsulation zone. We observe macrophage fusion to generate foreign body giant cells adjacent to the suture and this together with the degree of scarring is dependent on the biocompatibility of the suture used: sutures that induced more inflammation resulted in increased zones of avascularity and fibrosis. By genetically or pharmacologically modifying the inflammatory response we were able to minimise the FBR and normalise the status of the tissue surrounding these sutures. This new model of FBR in adult zebrafish allows us, for the first time, to live image the process and to modulate it in ways that may lead us towards new strategies to ameliorate and circumvent FBR in humans.