Delayed Bacterial Neutrophil Recruitment and Bacterial Bone Dispersion: New Identified Factors in Peri-Prosthetic Joint Infection Development. Insights From an Adult Minipig Model

Clinically relevant animal models of peri-prosthetic joint infection (PJI) are essential for studying infection initiation and progression. This study developed a PJI model in adult G & ouml;ttingen minipigs, explicitly focusing on the early stages of infection to gain new perceptions of PJI initiation. The model was established by drilling a hole into the femoral head, followed by inoculation with either Staphylococcus aureus (n = 6) or saline (n = 4) and inserting a stainless-steel screw. The animals were euthanized within 2 or 3 days post-inoculation. Comprehensive bone and joint pathology analyses were performed. All S. aureus inoculated animals had bacteria reisolated from bone, screw, synovial fluid, and synovial membrane. Histology revealed numerous bacterial colonies in the peri-implant bone tissue, many of which were unaccompanied by neutrophils, indicating delayed neutrophil recruitment to bacteria. In contrast, all synovial membrane-located bacteria were recognized by the immune system. Digital pathology measures showed deep bacterial dispersion within the bone, at a far distance from the point of inoculation. This study presents a new PJI model, which facilitates the investigation of infection initiation and supports studies aimed at preventing PJI. The study uncovered two previously unknown insights into the development of PJI: delayed bacterial neutrophil recruitment and widespread osseous bacterial dissemination within 48 h.