UNRAVELING THE INTERPLAY BETWEEN BIOLOGICAL MICROENVIRONMENT AND IMMUNE SYSTEM: THE ROLE OF ECM IN MACROPHAGE RESPONSE

In recent years, the role of biological microenvironment on the immune system response has garnered significant attention in the clinical field. Several studies suggest that a molecular-level comprehension of biological mechanisms that govern immune pathways could revolutionize therapeutic strategies. Since the extracellular matrix (ECM) modulates the behaviour of immune cells in healthy and diseased tissues, the study of interactions between immune cells and inflammatory stimuli should consider the extracellular microenvironment where these interactions occur. In the present work, our main goal is to study the role played by the microenvironment on the macrophage response to inflammatory inducers embedded in ECM. To this end, we developed ECM-like substrates based on denatured collagen loaded with increasing concentrations of carbon nanotubes (CNTs), as a model of inflammation-inducing fibers. The macrophage-like cells, derived from the human monocytic THP-1 cell line, were grown on the substrates up to 5 days. Preliminary experiments demonstrated that macrophages adhere to all substrates and that CNT treatments do not affect cell viability 24 hours after cell seeding. However, the cell morphology changed at higher CNT concentrations and culture times, showing an increase in filopodia and a decrease in spreading area taking on a round shape. Macrophages can remodel the ECM-like substrates, making CNTs bioavailable to be internalized as indicated by confocal and transmission electron microscopy imaging. Finally, conditioned media from THP-1 cells cultured in the presence of CNTs facilitated endothelial cell migration in the wound healing assay regardless conditioned media from control cells. Overall, functionalization of ECM-like substrates with CNTs can influence the activities of macrophages in a concentration-dependent manner suggesting macrophage activation.