The implant-related infection reduces the accumulation of mesenchymal stem cells near the implant site, while inhibiting the survival and osteogenic capabilities of these stem cells. We demonstrated that the pH-responsive biomaterial interface utilizes the acidification induced by infection to coordinate antibacterial effects with the reprogramming of stem cell and immune cell functions. This system can release bactericidal peptides to directly eliminate bacteria, while indirect bactericidal enhancement is carried out in the presence of magnesium ions and cell-targeting peptides, respectively promoting the positive regulation of the immune response and the recruitment of bone marrow mesenchymal stem cells. This feature leads to the osteogenic differentiation at the implant interface, resulting in a 280% increase in the interface bone volume in the rat infection model. Through transcriptomic analysis, we also showed that Wnt-activated stem cells and alternatively activated macrophages jointly upregulate the antibacterial effector programs, combined with bone-derived genes, promoting the combined inhibition mediated by the material and cells, achieving a reduction of >4-log bacteria. The coordinated infection clearance and interface regeneration indicate that the infection-responsive biomaterials can convert endogenous cells into dual-functional therapeutic agents, defining a strategy that views infection and regeneration as a comprehensive biological process. This study was published in Advanced Materials under the title "Immune and Stem Cell-Mediated Bactericidal Amplification and Bone Remodeling for Infection Clearance and Osteointegration".
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DOI: 10.1002/adma.72941