Magnetoelectric-bioactive dual functions of MXene regulate macrophage M1-M2 sequential polarization to promote healing of infected wound
Macrophages are pivotal in infection resolution and tissue repair via dynamic M1-to-M2 phenotypic polarization. Although various nano-biomaterials can modulate macrophage polarization, achieving sequential M1-to-M2 transition using a single nanoformulation remains challenging. Here, we propose a strategy employing transition metal carbide/nitride (MXene) nanosheets, internalized by macrophages, as the sole regulator to induce sequential polarization. Under a rotating magnetic field, the high electrical conductivity and magnetoelectric activity of endocytosed MXene generate electrical signals and reactive oxygen species (ROS), driving M1 polarization. Upon magnetic field removal, the inherent bioactivity of MXene facilitates repolarization to the M2 phenotype. Mechanistically, this transition involves inhibition of the NF-κB signaling pathway and activation of the JAK-STAT signaling pathway. In vivo, MXene nanosheets under on-off rotating magnetic field stimulation enabled sequential M1-to-M2 polarization, promoting bacterial clearance and tissue regeneration in infected wounds. This two-step sequential strategy targeting macrophages offers a promising therapeutic approach for infected wound healing.