UV-Grafted Polyitaconic Acid Functionalization of PEEK Promotes Osteoimmunomodulation and Osseointegration with PI3K-AKT-Associated Autophagy Regulation

Polyetheretherketone (PEEK) is a promising orthopedic implant material because of its favorable mechanical properties and biocompatibility, yet its bioinert surface limits osseointegration. Here, we develop a polyitaconic acid-functionalized PEEK surface (PEEK-PITAc) through a one-step ultraviolet-induced graft polymerization strategy to improve its osteoimmunomodulatory performance. The PITAc grafted PEEK surface exhibits enhanced hydrophilicity and bioactivity while maintaining its original morphology. In vitro, PEEK-PITAc modulates macrophage behavior toward a more pro-regenerative phenotype and establishes an immune microenvironment favorable for osteogenesis and angiogenesis. The modified surface also directly supports the osteogenic and angiogenic functions of relevant cells. Mechanistically, these effects are associated with autophagy-related changes and reduced PI3K-AKT pathway activation. In a rat femoral implantation model, PEEK-PITAc mediates a more favorable local immune response, promotes peri-implant bone formation, and improves osseointegration. Overall, this study shows that PITAc functionalization is a simple and effective strategy for endowing bioinert PEEK with enhanced osteoimmunomodulatory and bone-regenerative properties.