Whenever any foreign material is implanted in the body, this leads to inflammatory and fibrotic processes, i.e. the foreign body response (FBR). Macrophages play a crucial role in the FBR and are therefore a promising target for research purposes, to better understand the molecular mechanism by which biomaterials influence their physiology and to develop immune-instructive biomaterials to achieve desirable responses. Previous studies have shown that surface topography mediates immune responses to implants, but the molecular mechanism behind macrophage behavior is largely unknown. Therefore, this project will focus on elucidating the missing link between macrophage adhesion and subsequent signal transduction pathways leading to secretome adaptations. The TopoChip platform will be used to investigate the inter-relationship between surface topography and cell response. Emphasis will be placed on the role of integrin-mediated signaling in the phenotypic response of macrophages and their secretome adaptations. Additionally, the cross-talk between macrophages and fibroblasts will be studied to better understand the immune-driven fibrotic response.
Overall, this research aims to better understand how macrophages adhere to different surfaces at the molecular level and how this affects certain signal transduction pathways leading to their polarization and secretome adaptations.