Programmatic regulation of macrophage polarization by HAp@MXene nanocomposites to promote bone repair

Abstract Patients with large‐area bone defects are highly prone to infection, which significantly hinders healing. This study presents an innovative strategy that combines exogenous physical signals with implantable materials to achieve programmed immune modulation by dynamically regulating macrophage M1/M2 polarization, striking a balance between antibacterial activity and bone regeneration. Specifically, we synthesized HAp@MXene nanocomposites by integrating hydroxyapatite nanorods with MXene nanosheets, resulting in multifunctional materials with unique magnetoelectric properties and controlled Ca 2+ release. These nanocomposites exert their effects through cellular internalization, where magnetoelectric induction generates intracellular currents to promote macrophage M1 polarization, initiating a pro‐inflammatory response to mitigate infection risk. Subsequently, calcium ions are released within lysosomes, driving macrophage M2 polarization to facilitate anti‐inflammatory response and promote tissue regeneration. This dual‐modality mechanism achieves the precise programmatic regulation of macrophages, accelerates and optimizes the process of bone defect repair, and underscores the immense potential of HAp@MXene nanocomposites in synergistic antibacterial and bone regeneration therapies.