The immune response to implanted materials remains a critical challenge for the development of biomaterials used in medical devices and regenerative medicine. Understanding this response and designing better biomaterials requires a multidisciplinary approach involving materials engineering and immunology. The goal of our work is to understand how material properties regulate the function of immune cells, particularly macrophages, versatile regulators of the innate immune system that are involved in inflammation, wound healing, and tissue regeneration. Using cell micropatterning and surface topography, we have previously found that geometry of adhesion, or cell shape, plays a critical role in regulating their polarization towards pro-inflammatory versus pro-healing states. More recently, we have examined how the composition and architecture of three-dimensional extracellular matrices influence macrophage adhesion and function. In particular, we found that fibrin matrices are protective and inhibit macrophage inflammatory activation. Current work is focused on understanding mechanochemical signaling pathways involved, and leveraging these findings to design new materials to encourage macrophage-mediated wound healing.