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Macrophages play a crucial role in the fight against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    but suffer from deficiencies in function in the infectious milieu leading to persistent infection. Here, a strategy of exploiting aged neutrophil membrane (aNM) is developed to camouflage 2D MnPSe\n                    <jats:sub>3<\/jats:sub>\n                    nanosheets (MPS NSs), denoted as aNM@MPS, to mediate in situ macrophage engineering, thereby potentiating macrophages to eradicate refractory osteomyelitis. When administered systematically, the biofunctional aNM@MPS ensures selectivity for osteomyelitis lesions, enhanced bone marrow retention, and subsequent phagocytosis by macrophages. In the mouse model of osteomyelitis, the aNM@MPS enables dysfunctional macrophages to digest intracellular bacteria by generating highly toxic hydroxyl radicals and sequentially reprogramming bactericidal immunity through manganese ion\u2010mediated immune activation, which synergistically terminates persistent infection\u2010initiated pathological cascades and subsequently reestablish host\u2010directed bactericidal potency, thereby conferring a satisfactory osteoprotective effect. These findings demonstrate that macrophages in the skeletal infectious milieu can be precisely remodeled via the lesion\u2013macrophage dual\u2010targeting metalloimmunotherapy strategy, which holds potential for osteomyelitis treatment.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202500169","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T01:28:27Z","timestamp":1748914107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Manganese\u2010Based Biofunctional 2D Nanosheets Enabled In Situ Macrophage Engineering for Precise Eradication of Osteomyelitis"],"prefix":"10.1002","volume":"14","author":[{"given":"Shengchang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medical Technology Beijing Institute of Technology  Beijing 100081 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