Ion‐in‐Conjugation‐Enabled Remineralized Scaffold for Spatiotemporal Control of Infection and Bone Regeneration

Abstract Infectious bone defects remain a major clinical challenge requiring simultaneous infection control and bone regeneration. Here, a dual‐functional scaffold integrating antimicrobial and osteogenic activities is developed via sequential ion delivery. An acellular demineralized bone matrix (aDBM) is first remineralized with strontium phosphate (RBM) via an alternating solution immersion method, enhancing both mechanical strength and osteoinductivity. Subsequently, an ion‐in‐conjugation (IIC) polymer coating incorporating antimicrobial metal ions (Zn 2 ⁺ or Ni 2⁺ ) is synthesized in situ on the mineralized surface via a mild wet‐chemical reaction. This hybrid design confers the scaffold with a unique temporal bioactivity: the IIC coating enables controlled, sustained release of antibacterial ions, effectively eliminating Staphylococcus aureus , suppressing biofilm formation, and disrupting bacterial protein synthesis and metabolism; meanwhile, the underlying RBM layer promotes angiogenesis and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via activation of the PI3K‐AKT signaling pathway. In vivo, IIC‐coated RBM scaffolds (Zn/IIC‐RBM and Ni/IIC‐RBM) exhibit significantly enhanced bone regeneration and infection control in a rat calvarial defect model. This bioactive scaffold design offers a promising strategy for treating infection‐related bone injuries.