Cell Dynamics and Metabolism of the Foreign Body Response: Characterizing Host-Biomaterial Interactions for Next-Generation Medical Implant Biocompatibility

Implantable medical devices (IMDs) collectively represent a critical mainstay in modern medicine. Used in many chronic diseases and in acute surgical interventions, IMDs are often associated with improvements in disease progression, quality of life, and mortality rates. Despite the positive impacts of IMD implementation, excessive fibrosis driven by the foreign body response (FBR) is frequently associated with the development of complications and failure. These complications in turn result in surgical revisions and removals, which represent a significant burden to healthcare costs and surgical wait-times in countries with elevated IMD usage rates. IMD complications are exacerbated by limitations to treatment options and limited availability of biocompatible materials. Novel treatment development is equally hampered by the complexity of the FBR, wherein complex cellular behaviors defy canonical immunological classification systems. In this review, current understandings of cellular dynamics and kinetics within the FBR are summarized, with a specific focus on the relationship between immunometabolic regulation and pathological fibrotic processes across various cell behaviours in the FBR. This review also explores promising emerging in vitro and in vivo techniques of FBR characterization, and highlights biomaterial properties associated with alterations in FBR outcomes. Finally, this review explores current and future approaches to biocompatible material development, highlighting immune-metabolic control as a therapeutic approach to mitigating the FBR.