Surface microstructure of PEEK scaffolds regulates osteogenic differentiation via the βPIX-RAC1-NOX1 pathway.

Polyetheretherketone (PEEK) is widely applied in orthopedic implants, yet its intrinsic surface bioinertness limits stable osseointegration. Although a nature solution is modifying its surface to enhance cellular adhesion, other pathways related to osseointegration also hold significant value. Here, we combined fused deposition modeling (FDM) 3D printing with a two-step poly (acrylic acid)-ethylenediamine (PAA-EDA) grafting method to engineer porous PEEK scaffolds with bioactive surface microstructures. Beyond improving hydrophilicity to optimize cellular adhesion, the modified surface activated the βPIX-mediated signaling cascade, which suppressed ITGB1-RAC1-NOX1 activity, potentially delaying bone mesenchymal stem cell (BMSC) senescence and promoting osteogenic differentiation. In vivo implantation further validated that the modified scaffolds promoted bone formation and integration. Together, this work highlights a new pathway on osseointegration for PEEK surface engineering, revealing the potential of βPIX-mediated regulation as a new direction for durable bone-implant integration.