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Polyetheretherketone (PEEK) is widely used in orthopedics, yet its clinical applications are restricted due to its poor osteogenic and antibacterial properties as well as inadequate immune responses. To overcome these drawbacks, a novel spatiotemporal immunomodulation approach is proposed, chelating Cu\u2013Sr bilayer bioactive glass nanoparticles (CS\u2010BGNs) onto the PEEK surface via polydopamine (PDA). The CS\u2010BGNs possess a bilayer core\u2013shell structure where copper is distributed in the outer layer and strontium is clustered in the inner layer. The results show that CS\u2010BGNs\/PDA functionalized PEEK demonstrates a controlled and sequential release of Cu<jats:sup>2+<\/jats:sup> and Sr<jats:sup>2+<\/jats:sup>. In the early\u00a0stage, Cu<jats:sup>2+<\/jats:sup> from the outer layer releases rapidly, while Sr<jats:sup>2+<\/jats:sup> from the inner layer releases in the late stage. This well\u2010ordered release pattern modulates the phenotypic transition of macrophages, which induces M1 polarization in the early stage and M2 polarization in the late stage. Combined with the direct effects of Cu<jats:sup>2+<\/jats:sup> and Sr<jats:sup>2+<\/jats:sup>, the spatiotemporal immunomodulation not only benefits the early antibacterial and tissue\u2010healing process, but also promotes the long\u2010term process of osseointegration, providing new perspectives on the design of novel immunomodulatory biomaterials.<\/jats:p>","DOI":"10.1002\/adhm.202301772","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T01:40:15Z","timestamp":1695087615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Cu\u2013Sr Bilayer Bioactive Glass Nanoparticles\/Polydopamine Functionalized Polyetheretherketone Enhances Osteogenic Activity and Prevents Implant\u2010Associated Infections through Spatiotemporal Immunomodulation"],"prefix":"10.1002","volume":"12","author":[{"given":"Yuezhou","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Bone 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