Antibacterial and Immunomodulatory Coatings for Orthopedic Metal Implants: Biological Rationale, Design Strategies, and Translational Challenges.

Orthopedic metal implants are central to fracture fixation, bone-defect reconstruction, and joint replacement, but their long-term performance remains limited by implant-associated infection, biofilm persistence, foreign body response, and impaired osseointegration. This review reframes antibacterial and immunomodulatory coatings as regulators of a dynamic implant biointerface rather than as isolated bactericidal or drug-eluting layers. We first outline the biological coupling among protein conditioning, bacterial adhesion, biofilm maturation, macrophage-mediated inflammation, corrosion, surface topography, and bone integration. We then summarize design requirements for orthopedic metal implant coatings, including cytocompatibility, anti-biofilm efficacy, immune balance, osteogenic support, mechanical adhesion, wear durability, and electrochemical stability. Antibacterial strategies are discussed according to ion-releasing and metal oxide coatings, bioceramic and bioactive glass-based systems, antimicrobial cargo delivery, contact-killing and anti-adhesive surfaces, and externally activated responsive coatings. Immunomodulatory strategies are organized around local anti-inflammatory delivery, natural molecules, cytokine or growth factor presentation, ion-mediated osteoimmunomodulation, and redox or thermal regulation. Finally, we highlight multifunctional coating architectures, fabrication-dependent structure-function relationships, integrated validation frameworks, and translational barriers. This Review provides a design-oriented framework for developing clinically translatable orthopedic implant interfaces that coordinate infection control, immune regulation, osseointegration, and long-term stability.