Plasma-Induced Amine-Modified PEEK Promotes Osteointegration via Multiple Osteogenic Pathways and Macrophage...

Polyetheretherketone (PEEK) is a semicrystalline synthetic polymer commonly used in orthopedic devices because of its chemical stability, thermal elasticity, radiopacity, and mechanical moduli similar to that of bone. However, its inherent biological inertness results in poor initial fixation and insufficient bone bonding, which can compromise implant stability and long-term success. To overcome this limitation, various surface modification strategies, such as physical treatments (for example, sandblasting or sulfonation) and coating deposition of titanium or hydroxyapatite, have been explored. However, physical modification makes it difficult to control surface roughness uniformity, and coatings risk generating wear debris in vivo, which may inhibit surrounding bone formation and cause bone resorption. To address these challenges, PEEK was modified via plasma-enhanced chemical vapor deposition using CH₄/N₂ gas to deposit a uniform carbonaceous thin film containing amine groups, and its osteogenic effects and underlying mechanisms were investigated. Plasma-treated PEEK demonstrates enhanced hydrophilicity and cell adhesion without altering surface roughness and promotes osteoblastic differentiation compared to untreated PEEK in vitro. Analysis of the mechanisms promoting osteoblastic differentiation using RNA sequencing revealed the activation of FAK signaling associated with cell adhesion and the independent upregulation of the BMP4/Smad signaling pathway. In vivo implantation into rat femurs demonstrated that untreated PEEK exhibited fibrous tissue intervention at the PEEK-bone interface, whereas plasma-treated PEEK showed bone formation without fibrous tissue intervention as early as 2 weeks postoperatively. Moreover, at 6 weeks postimplantation, plasma-treated PEEK exhibited superior quality bone formation compared to untreated PEEK. These findings suggest that plasma treatment effectively enhances the osteogenic potential of PEEK, addressing its inherent biological inertness and highlighting its potential as a next-generation biomaterial for orthopedic implants.