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

Abstract

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.