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Here, we engineer an intelligent pH\u2010responsive MXene\u2010based nanosystem (MPDM) integrating polyethyleneimine (PEI) for pathogen\u2010derived cfDNA capture, methyltransferase\u2010like 3\/14 (METTL3\/14) for m6A\u2010mediated osteogenic reprogramming, and 2,3\u2010dimethylmaleic anhydride (DMMA) for dynamic charge\u2010shielding to enhance targeting of inflammatory sites targeting. In vitro studies reveal that MPDM exhibits synergistic antibacterial activity, potent reactive oxygen species (ROS) scavenging capacity, and inflammation\u2010triggered payload release. In a murine ligature\u2010induced periodontitis model, micro\u2010CT analysis revealed that MPDM reduced alveolar bone loss and increased the bone volume fraction by 32% (from 53% to 85%) compared to the diseased (Untreated) group. Transcriptomic analysis further reveals that MPDM downregulates toll\u2010like receptor (TLR) and neutrophil extracellular trap (NET) formation signaling pathways, while suppressing osteoclast differentiation. By concurrently neutralizing pathogenic triggers and activating tissue repair, this work establishes a framework for next\u2010generation nanotherapeutics in inflammatory bone disorders, with potential applicability to other multifactorial diseases.<\/jats:p>","DOI":"10.1002\/adhm.202505749","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:33:39Z","timestamp":1770964419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Intelligent MXene Nanoplatform for Bone Regeneration in Periodontitis Through Synergistic Scavenging Pathogenic cfDNA and ROS"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7756-8639","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Clinical Research Center for Oral Diseases Department of Orthodontics School of Stomatology The Fourth Military Medical University  Xi'an P. 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