Poly(ether ether ketone) (PEEK) is a biocompatible polymer, but the lack of angiogenesis makes the long-term osteogenic fixation of PEEK implants challenging, which has hampered their wider application in orthopedics. Herein, we develop a multifunctional micro-/nanostructured surface presenting hydroxyapatite (HA) nanoflowers and nickel hydroxide (Ni(OH) 2 ) nanoparticles on PEEK implants (sPEEK-Ni-HA) to tackle the problem. The results show that the reasonable release of Ni 2+ from sPEEK-Ni-HA significantly facilitates the migration, tube formation, and angiogenic gene expression of human umbilical vein endothelial cells (HUVECs). In addition to angiogenesis, the sPEEK-Ni-HA displays enhanced cytocompatibility and osteogenicity in terms of cell proliferation, spreading, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene secretion, exceeding pure and other multifunctional sPEEK samples. Importantly, in vivo evaluations employing a rabbit femoral condyle implantation model confirm that such dual decoration of Ni elements and HA nanoflowers boosts bone remodeling/osseointegration, which dramatically promotes the in vivo osteogenic fixation of implants. Therefore, this work not only sheds light on the significance of angiogenesis on the osteogenic fixation of an implant but also presents a facile strategy to empower bioinert PEEK with a well-orchestrated feature of angiogenesis and osteogenesis.

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