Phage Therapy for Bone and Joint Infections: Towards Clinical Translation

Osteoarticular infections (OAIs), including osteomyelitis, septic arthritis, prosthetic joint infections, and facture-related infections, remain a major challenge due to biofilm formation and the prevalence of multidrug-resistant (MDR) pathogens. Although OAIs are predominantly caused by <i>Staphylococcus aureus</i> and coagulase-negative staphylococci, the increasing incidence of MDR Gram-negative infections adds further complexity to their management. Standard approaches, combining surgery and prolonged antibiotic therapy, frequently result in recurrence and poor outcomes. Bacteriophage (phage) therapy has emerged as a promising adjunct or alternative approach, offering high host specificity, replication at the infection site, and activity against biofilm-embedded bacteria. This review highlights recent advances in phage therapy for OAIs, focusing on administration routes (intravenous, intra-articular, topical, and oral) and on novel pharmaceutical delivery systems such as hydrogels, bone cements, microparticles, nanoparticles, and implant coatings. Preclinical and early clinical studies have analyzed phage stability, controlled release, and the synergistic effects of combined phage/antibiotic therapy. However, challenges remain regarding standardization, immunogenicity, and regulatory approval. Nonetheless, phage therapy shows promise for clinical translation as an adjunct or alternative to conventional treatments for OAIs. Well-designed clinical trials are urgently needed to confirm the efficacy of phage therapy, optimize delivery strategies, and integrate the treatments in routine practice. Despite encouraging outcomes for a successful clinical implementation, regulation and standardization of GMP production are required.