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Here, we developed a multifunctional biomimetic Trojan horse nanosystem based on hydroxyapatite nanotubes (NT\u2010HA) for microenvironment remodeling. The NT\u2010HA exhibits a dual\u2010stage antimicrobial peptide (AMP) delivery strategy, in which surface\u2010adsorbed AMPs are rapidly released to eliminate extracellular bacteria, while NT\u2010HA is internalized via endocytosis to release encapsulated AMPs for efficient intracellular bacterial clearance. After releasing AMPs, the NT\u2010HA can regulate the PI3K\u2010AKT signaling cascade, promoting the directed osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells (OBMSCs). In the repair of infected osteoporotic bone defects in vivo, this Trojan horse nanosystem not only enhances bone regeneration by eliminating cellular infections and inducing OBMSCs osteogenesis but also reduces peri\u2010implant bone loss and strengthens bone strength, ultimately remodeling the regenerative microenvironment to achieve optimal bone defect repair and functional reconstruction.<\/jats:p>","DOI":"10.1002\/adma.74669","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:57:30Z","timestamp":1788328650000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multifunctional Biomimetic Trojan Horse Nanosystem for Remodeling Infected Regenerative Microenvironments in Osteoporotic Bone Defects"],"prefix":"10.1002","author":[{"given":"Yongdi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery and Orthopedic Research Institute West China Hospital, Sichuan University  Chengdu China"},{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyang","family":"Liao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu China"},{"name":"School of Biomedical Engineering Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu China"},{"name":"School of Biomedical Engineering Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu China"},{"name":"School of Biomedical Engineering Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2957-8681","authenticated-orcid":false,"given":"Shan","family":"Gong","sequence":"additional","affiliation":[{"name":"Pittsburgh Institute Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Kaisheng New Materials Co., Ltd.  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