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Here, we show that pH\u2010responsive biomaterial interfaces exploit infection\u2010induced acidification to coordinate antimicrobial action with stem and immune cell functional reprogramming. The system can release bactericidal peptides for direct bacterial elimination, whereas indirect bactericidal enhancement occurs in the presence of magnesium ions and cell\u2010targeting peptides, which enable a positive modulation of immune responses and recruitment of bone marrow mesenchymal stem cells, respectively. This feature results in robust osteogenic differentiation at the implant interfaces, achieving a 280% increase in the interfacial bone volume in rat infection models. Through transcriptomic analysis, we also show that Wnt\u2010activated stem cells and alternatively activated macrophages jointly upregulate antimicrobial effector programs along with osteogenic genes, contributing to the observed &gt;4\u2010log bacterial reduction through combined material\u2010 and cell\u2010mediated suppression. The coordinated infection clearance and interface regeneration demonstrate that infection\u2010responsive biomaterials can transform endogenous cells to bifunctional therapeutic agents, defining a strategy that addresses infection and regeneration as integrated biological processes.<\/jats:p>","DOI":"10.1002\/adma.72941","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:56:09Z","timestamp":1774688169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune and Stem Cell\u2010Mediated Bactericidal Amplification and Bone Remodeling for Infection Clearance and Osteointegration"],"prefix":"10.1002","volume":"38","author":[{"given":"Zhenyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui P. R. 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