Orthopedic Implant Infection Management: Prevention, Barrier Breakthrough, and Immunomodulation.

The widespread use of biomedical implants has led to a surge in implant-associated infections, particularly in orthopedic applications, where biofilm formation, antibiotic resistance, and immune dysregulation synergistically exacerbate therapeutic challenges, increasing patient morbidity and healthcare burdens. This review delineates the pathogenic mechanisms, especially for Staphylococcus aureus, underpinning microbial persistence in orthopedic implant infections. Key mechanisms include biofilm-mediated physical barrier formation, abscesses, invasion of the osteocyte lacuno-canalicular network, and immune evasion that shield pathogens from antimicrobial agents and host defenses. We also outline recent advancements in infection, strategies to overcome physical barriers, such as biofilms and abscesses, and interventions aimed at modulating host immune responses to enhance bacterial clearance and tissue repair. By integrating perspectives from microbiology, immunology, and biomaterials science, we advocate for a paradigm shift toward multidimensional therapeutic approaches that synergistically address infection prevention, barrier penetration, and immune regulation. Such an integrated strategy is essential for tackling this critical and growing clinical challenge in orthopedic medicine.