A Surface-Mediated\nBiomimetic Porous Polyether–Ether–Ketone\nScaffold for Regulating Immunity and Promoting Osteogenesis

The repair of critical-sized bone defects remains a major\nchallenge\nfor clinical orthopedic surgery. Here, we develop a surface biofunctionalized\nthree-dimensional (3D) porous polyether–ether–ketone\n(PEEK) scaffold that can simultaneously promote osteogenesis and regulate\nmacrophage polarization. The scaffold is created using polydopamine\n(PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic\nself-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed\nporous PEEK scaffold. The SF/nano-HA functionalized surface provides\na bone-like microenvironment for osteoblastic cells’ adhesion,\nproliferation, mineralization and osteogenic differentiation. Moreover,\nthe biofunctionalized surface can effectively drive macrophages polarization\nfrom the pro-inflammatory M1 phenotype to the anti-inflammatory M2\nphenotype. Integrin β1-specific cell-matrix binding and the\nactivation of Ca<sup>2+</sup> receptor-mediated signaling pathway\nplay critical roles in the regulation of macrophage polarization.\nCompared with the as-printed scaffold, the SF/nano-HA functionalized\nporous PEEK scaffold induces minimal inflammatory response, enhanced\nangiogenesis, and substantial new bone formation, resulting in improved\nosseointegration <i>in vivo</i>. This study not only develops\na promising candidate for bone repair but also demonstrates a facile\nsurface biofunctionalization strategy for orthopedic implants to improve\nosseointegration by stimulating osteogenesis and regulating immunity.