Complementary Activities of Bacteriophages and Antimicrobial Peptide Dendrimers Against Prosthetic Joint Infection Pathogens

Prosthetic joint infections (PJIs) remain a major challenge in orthopedic surgery due to the increasing prevalence of antimicrobial-resistant pathogens and their ability to form biofilms on implant surfaces. Local delivery of non-traditional antimicrobials through implant-associated biomaterials represents a promising strategy for preventing bacterial colonization while minimizing systemic antibiotic exposure. This study evaluated the antimicrobial activity and cytocompatibility of two bacteriophages (Phage K and Phage F1) and two antimicrobial peptide dendrimers (AMPDs; TNS18 and G3KL) against clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis recovered from PJIs. Antimicrobial efficacy was assessed using solid and liquid culture assays, while cytocompatibility was evaluated using human osteoblast progenitor cells. Biofilm formation was also investigated under various in vitro conditions. Phages K and F1 demonstrated strong antibacterial activity against S. aureus isolates, whereas TNS18 showed pronounced inhibitory effects against S. epidermidis. All agents exhibited appropriate osteoblast compatibility, except Phage F1, at the highest multiplicity of infection tested. Biofilm formation was observed under several culture conditions, although substantial variability in biofilm stability limited the quantitative assessment of antimicrobial activity. These findings demonstrate complementary antimicrobial activity profiles between bacteriophages and AMPDs and support their further investigation as candidates for implant-associated antimicrobial delivery systems and orthopedic implant coatings.