Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway

The stiffness of the extracellular matrix (ECM) plays an important role in regulating the cellular programming. However, the mechanical characteristics of ECM affecting cell differentiation are still under investigated. Herein, we aimed to study the effect of ECM substrate stiffness on macrophage polarization. We prepared polyacrylamide hydrogels with different substrate stiffness, respectively. After the hydrogels were confirmed to have a good biocompatibility, the bone marrow-derived macrophages (BMMs) from mice were incubated on the hydrogels. With simulated by the low substrate stiffness, BMMs displayed an enhanced expression of CD86 on the cell surface and production of reactive oxygen species (ROS) in cells, and secreted more IL-1β and TNF-α in the supernatant. On the contrary, stressed by the medium stiffness, BMMs expressed more CD206, produced less ROS, and secreted more IL-4 and TGF-β. In vivo study by delivered the hydrogels subcutaneously in mice, more CD68