DELAYED NEUTROPHIL RECRUITMENT: A NEW COMPONENT IN THE DEVELOPMENT OF PERIPROSTHETIC JOINT INFECTION (PJI)

Aim To develop a clinically relevant periprosthetic joint infection (PJI) model in adult minipigs, with focus on the early stages of infection to gain new perceptions of PJI development. Method The study was conducted in adult Göttingen minipigs. A cavity measuring 2x15 mm was drilled into the femoral head, followed by the inoculation of either Staphylococcus aureus (n=6) or saline (n=4). A stainless-steel screw was then inserted into the cavity, with the head countersunk into the cartilage. This method allowed for the examination of all relevant PJI compartments (bone, synovial fluid, and synovial membrane). All animals were euthanized two- or three days after inoculation. Comprehensive microbiology and pathology analyses were performed, including digital pathology assessment of bacterial aggregates. Results From all animals inoculated with S. aureus the inoculated strain was re-isolated from the bone, screw, synovial fluid, and synovial membrane, while all saline-inoculated animals remained sterile. The histological examination revealed numerous bacterial colonies in the peri-implant bone tissue with delayed recruitment of neutrophils (Figure 1). In contrast, all bacteria located in the synovial membrane were accompanied by infiltration by neutrophils. Each of the six infected animals had more than 20 undiscovered peri-implant bacterial colonies of more than 30 µm 2 , i.e. the size of biofilms identified in human PJI biopsies and associated with impaired phagocytosis. Conclusions The minipig PJI model is highly applicable as it allows for investigating the early interplay between neutrophils and bacteria in adult species with a comparable immune system to humans. There is a delay in recruitment of neutrophils to bacteria following surgical contamination in orthopaedic surgery, and during this delay, the bacteria can form aggregates of mature biofilm sizes. This knowledge adds to explain the development of slow-onset infections and chronicity seen in PJI. For any figures or tables, please contact the authors directly.