Abstract Description The biological defense system that regulates immune responses plays a critical role in maintaining tissue homeostasis and influencing disease progression. In this study, we developed a novel biocompatible material designed to specifically modulate immune responses and investigated its underlying mechanism of action. Using mouse primary bone marrow-derived macrophages (BMDMs) and THP-1 cells, we explored the material’s ability to influence macrophage polarization toward the pro-inflammatory M1 phenotype. Our results show that the material significantly inhibited the expression of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, by disrupting key signaling pathways involved in macrophage activation. Moreover, in a mouse model of imiquimod (IMQ)-induced psoriasis, the material effectively reduced epidermal hyperplasia and inflammation, with these effects being dependent on MyD88 signaling. Mice treated with a MyD88 inhibitor exhibited diminished responses to the material, confirming the involvement of this pathway. Our findings indicate that this novel material modulates macrophage polarization and inflammatory responses through a distinct mechanism, offering valuable insights for developing innovative strategies to control inflammation-driven skin conditions. Funding Sources This study was supported by the National Research Foundation of Korea (NRF) grants (RS-2024-00411474) funded by the Ministry of Science and ICT. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)