NIR‐Responsive Nano‐Integrated Magnesium Phosphate Cement Promotes Bone Regeneration via Osteoblast‐Exosome‐Osteoclast Crosstalk

ABSTRACT The limited osteogenic capacity of magnesium phosphate cement (MPC) has constrained its biomedical applications, underscoring the necessity to develop MPC with enhanced physical properties and bone‐forming capabilities. In this study, a multifunctional MPC system was developed by incorporating zoledronic acid‐loaded near‐infrared (NIR)‐responsive nanocarriers, strontium oxide (SrO), and hyaluronic acid (HA). The nanocarriers were constructed using dual‐layer poly‐dopamine (PDA) modification of mesoporous silica nanoparticles (MSNs), enabling controlled drug release and antibacterial efficacy under NIR stimulation. The optimized Sr‐ZMP‐HA MPC demonstrated prolonged setting time, near‐neutral pH, superior injectability, and improved compressive strength. Immersion tests revealed its sustained degradation resistance. This composite material exhibited excellent biocompatibility along with enhanced osteogenic and angiogenic properties, particularly when activated by NIR irradiation. The experiments demonstrated that NIR‐triggered Sr‐ZMP‐HA MPC promoted osteoblast‐derived exosome secretion. These exosomes mediated miRNA transfer to osteoclasts, effectively suppressing their proliferation and differentiation while delaying bone tissue senescence. This dual‐functional system, combining NIR‐responsive nanomedicine with exosome‐mediated intercellular communication, provided a novel strategy for developing advanced bone repair materials, potentially addressing current limitations in orthopedic applications through synergistic mechanical reinforcement and biological activation mechanisms.