Dual-Functional Micro-Nano CFR-PEEK: Promoting Hippo-Mediated Osseointegration while Inhibiting P. gingivalis and Osteoclastogenesis

To construct a biomimetic hierarchical topography on carbon fiber-reinforced polyetheretherketone (CFR-PEEK) to enhance multifaceted biological performance, CFR-PEEK substrates were modified via a one-step nitration-sulfonation treatment using mixed nitric and sulfuric acids at various volume ratios. The resulting surface topographies were systematically evaluated for in vitro bioactivity (osteogenesis, angiogenesis, osteoclast inhibition, and antibacterial activity), and molecular mechanisms via RNA sequencing, alongside in vivo validation using a rat cranial defect model. A nitric-to-sulfuric acid ratio of 1:4 yielded a unique nanocluster-interspersed three-dimensional porous architecture. Upon cell-material interaction, this tailored surface upregulated osteogenic gene expression (RUNX-2, ALP, OCN) by suppressing the Hippo pathway and driving YAP/TAZ nuclear translocation. The 1:4 topography robustly enhanced endothelial cell migration and tube formation, while disrupting actin rings to suppress osteoclastogenesis (reducing TRAP and Cathepsin K expression) and selectively inhibiting Porphyromonas gingivalis colonization. In vivo evaluations confirmed accelerated bone mineralization, minimized osteoclast activation, and enhanced functional vascularization at the bone-implant interface. Overall, the optimized 1:4 mixed-acid etching endows CFR-PEEK with a bioactive micro-nano hierarchical surface. By precisely orchestrating the Hippo-YAP/TAZ mechanotransduction axis, this unique architecture balances osteogenesis, angiogenesis, anti-osteoclastogenesis, and targeted antibacterial activity, offering a highly efficient and clinically translatable surface modification strategy for next-generation dental implants.