Bio-Activated PEEK: Promising Platforms for Improving Osteogenesis through Modulating Macrophage Polarization

The attention on orthopedic biomaterials has shifted from their direct osteogenic properties to their osteoimmunomodulation, especially the modulation of macrophage polarization. Presently, advanced technologies endow polyetheretherketone (PEEK) with good osteoimmunomodulation by modifying PEEK surface characteristics or incorporating bioactive substances with regulating macrophage polarization. Recent studies have demonstrated that the fabrication of a hydrophilic surface and the incorporation of bioactive substances into PEEK (e.g., zinc, calcium, and phosphate) are good strategies to promote osteogenesis by enhancing the polarization of M2 macrophages. Furthermore, the modification by other osteoimmunomodulatory composites (e.g., lncRNA-MM2P, IL-4, IL-10, and chitosan) and their controlled and desired release may make PEEK an optimal bio-activated implant for regulating and balancing the osteogenic system and immune system. The purpose of this review is to comprehensively evaluate the potential of bio-activated PEEK in polarizing macrophages into M2 phenotype to improve osteogenesis. For this objective, we retrieved and discussed different kinds of bio-activated PEEK regarding improving osteogenesis through modulating macrophage polarization. Meanwhile, the relevant challenges and outlook were presented. We hope that this review can shed light on the development of bio-activated PEEK with more favorable osteoimmunomodulation.