Dual-Functional Cu-Engineered CFR-PEEK Interfaces Combat Infection and Orchestrate Vascularized Bone Regeneration via Osteoimmunomodulation

Abstract

Constructing a bioactive interface on bio-inert polyetheretherketone (PEEK) to concurrently counteract bacterial infection and orchestrate favorable osteoimmunomodulation remains a formidable challenge. Here, we engineer a hierarchical micro/nano-topography on carbon fiber-reinforced PEEK (CFR-PEEK) via acid etching, followed by gradient magnetron sputtering of copper (Cu) to establish a dual-physical/chemical platform. The optimal Cu-loaded surface, featuring a sustained release profile, achieves a delicate dose–effect balance that effectively disrupts Porphyromonas gingivalis biofilms while preserving superb cytocompatibility. Critically, we elucidate a synergistic "dual-engine" mechanism: this surface instructs pro-reparative macrophage polarization (evidenced by CD206 upregulation) and orchestrates a paracrine niche. Through robust activation of the FAK/PI3K/Akt signaling cascade and concomitant suppression of the pro-inflammatory NF-κB pathway, it synergistically potentiates both the osteogenic commitment of rBMSCs and angiogenic network formation by EA.hy926 cells in vitro. In a rat calvarial defect model, the functionalized implant profoundly accelerates vascularized bone regeneration, achieving a bone volume fraction (BV/TV) of 20.63 ± 0.89%—a nearly 3-fold increase over the pristine PEEK control (P < 0.001). By coupling topographical cues with controlled Cu-ion release, this strategy redefines bio-inert PEEK as a dynamic osteoimmune microenvironment modulator, offering a compelling paradigm for next-generation orthopedic implants that integrate potent antibacterial defense with robust regenerative capacity.