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By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron\u2010overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush\u2010like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self\u2010assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre\u2010osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP\/\u03b2\u2010catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron\u2010overloaded osteoporotic rabbits and supported by in vitro validations.<\/jats:p>","DOI":"10.1002\/adma.202406227","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T21:21:04Z","timestamp":1724275264000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis"],"prefix":"10.1002","volume":"36","author":[{"given":"Xingyu","family":"Zhou","sequence":"first","affiliation":[{"name":"Engineering Research Center of Special Engineering Plastics Ministry of Education College of Chemistry Jilin University  Changchun 130012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Special Engineering Plastics 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