Dual-functional Ti coating with spatiotemporal antibacterial activity and osteoimmune modulation for implant-related infection

• A stepwise surface modification strategy was applied to prosthetic Ti surfaces. • The Ti coating has an outer layer of Cu 2 O and an inner E7-KR12 peptide layer. • KR12 kills bacteria, Cu 2 O stimulates immune response, and E7 regenerates tissue. • Cu 2 O-E7KR12 Ti coating has antibacterial and osteoimmune modulation properties. • Infections successfully inhibited by coating Ti prosthetic with Cu 2 O-E7KR12. Stimulating bone regeneration post-orthopedic implantation while inhibiting infections, particularly those caused by multidrug-resistant Staphylococcus aureus , remains a major clinical challenge in orthopedic surgery. To ensure bone integration, the anti-infection property of orthopedic implants must be suppressed; conversely, to enhance anti-infection performance, the bone integration performance must be lowered. To this end, we developed a multifunctional Ti surface coating comprising Cu(I) oxide (Cu 2 O) nanoparticles and E7-KR12 peptide. Characterization and in vitro and in vivo assay results revealed that this multifunctional coating exhibited on-demand spatiotemporal antibacterial action and osteoimmune modulation: Cu 2 O provided early-stage bactericidal activity and promoted M1-type macrophage polarization, enhancing immune-mediated bacterial clearance, while E7-KR12 was comprised of an antimicrobial peptide (KR12) and a bone marrow mesenchymal stem cell adhesion-promoting peptide (E7). During the healing phase, the E7-KR12 coating promoted rat bone marrow-derived mesenchymal stem cells (rBMSC) recruitment, macrophage M2 polarization, and osteogenic differentiation. In vitro studies confirmed strong antibacterial activity, favorable immunomodulation, and enhanced osteogenesis. In an implant-related infection model, the multifunctional Ti coating reduced the bacterial burden, suppressed inflammation, and promoted robust bone regeneration. Therefore, this study formulated a novel Ti coating with on-demand spatiotemporal antibacterial action and osteoimmune modulation, demonstrating translational potential for orthopedic implants in infection-prone environments