Biomimetic Chiral Nanotopography for Manipulating Immunological Response

Immune response regulates implanted biomaterial−tissue integration and tissue regeneration, in which macrophages play a key role due to their plasticity and polarization. Chirality, an inherent property of carbon‐based life, can also exist in biomaterials such as gold monolayer. Constructing chiral nanostructured surfaces of implants can imitate the chirality of extracellular environment in a biomimetic manner, but the manipulation and mechanism of chiral nanotopography on macrophages remain poorly understood. Here, highly ordered gold nanoparticle arrays with 300 or 900 nm spacing are fabricated and modified with L‐ or D‐chirality. The D‐nanoarrays can promote M2 polarization and related cytokine secretion of macrophages, thus facilitating the reduction of inflammatory reaction and promoting tissue healing and regeneration. The mechanistic analysis further suggests that D‐nanoarrays proceeded these regulations through enhancing the expression of integrin αv/α8/β3‐p‐FAK pathway in macrophages, which may be largely attributed to its higher stereo‐affinity for fibronectin as revealed by quantitative experiments and molecular dynamics simulations. Overall, this study demonstrates that biomimetic chiral nanotopography can promote biomaterial−tissue integration by manipulating macrophage phenotype, bringing a novel strategy for immunomodulation. Highly ordered gold nanoparticle (AuNP) arrays with L‐ or D‐chirality imitate the chirality of extracellular environment in a biomimetic manner. Due to the higher stereo‐affinity for fibronectin, the D‐nanoarrays enhance the expression of integrin αv/α8/β3‐p‐FAK pathway in macrophages and promote M2 polarization and related cytokine secretion of macrophages, thus facilitating promoting bone tissue healing and regeneration.