Abstract

3D-printed polyetheretherketone (PEEK) scaffolds hold great promise for personalized bone repair owing to their excellent mechanical properties and highly tunable porous architectures. However, their intrinsic bioinertness severely limits osseointegration and long-term clinical efficacy. We have developed an innovative bioactive scaffold (SIM@MPSP) by engineering a multifunctional biointerface onto 3D-printed porous PEEK. The biointerface consists of a polydopamine-anchored bimetallic (MgCu) metal-organic framework (MOF) coating that enables efficient loading and sustained release of simvastatin (SIM), Mg 2+ , and Cu 2+ . The coordinated release of these agents creates a therapeutically conducive microenvironment that promotes osteogenesis and angiogenesis, while reprogramming macrophages from a pro-inflammatory M1 phenotype to a pro-regenerative M2 state through modulation of both canonical and non-canonical NF-κB pathways. This immune-regulatory process effectively mitigates inflammation and rescues inflammatory suppression of osteogenesis, thereby establishing a favorable osteoimmunomodulatory niche. SIM@MPSP demonstrated excellent biocompatibility, significantly attenuated foreign-body responses, and enabled robust bone regeneration in in vivo models. Mechanistically, the scaffold facilitates deep bone growth throughout its porous network and forms an interlocked interface with native bone, thereby achieving robust osseointegration. This study presents a powerful biointerface engineering strategy for converting bioinert PEEK into a bioinstructive platform capable of orchestrating coordinated osteogenic, angiogenic, and immunomodulatory responses, thus offering new opportunities for personalized treatment of complex bone defects.