Dual-functional polyetheretherketone surface modification for regulating immunity and bone metabolism

Polyetheretherketone (PEEK) has gained increased attention as an orthopedic implant material in recent years. However, the adverse inflammatory and immunological reactions elicited by the PEEK surface result in inferior osteointegration and affect its clinical utility. To improve osseointegration and enhance the success rate of PEEK implants, the surface can be biofunctionalized to be immunomodulatory. Herein, A-485, a potent and selective catalytic inhibitor of p300/CBP, was loaded into mesoporous bioactive glass that had been immobilized on the PEEK surface, and the immunomodulatory capability and effects of the biofunctionalized PEEK implants on osteointegration were evaluated. In vitro, the biofunctionalized PEEK surface not only suppressed the acute inflammatory response of macrophages, but also inhibited bone resorption and promoted osteogenesis, indicating that it plays critical and complex roles in maintaining normal bone metabolism. Moreover, the biofunctionalized surface induced less fibrous capsule formation and exhibited superior osseointegration properties in vivo. The A-485-loaded MBG-biofunctionalized PEEK surface attenuated inappropriately activated immune responses mediated by macrophages and subsequently inhibited osteoclastogenesis, promoting osteogenesis and yielding superior osseointegration. Therefore, these surface-biofunctionalized PEEK implants, which regulate both immunity and bone metabolism, demonstrate strong potential for clinical application as orthopedic implants.