Introduction: Osteomyelitis remains a major clinical challenge and high burden disease in orthopaedic and trauma patients, particularly when the infection is associated with antimicrobial resistance and biofilm contamination. Multiple strategies are being explored to improve infection prophylaxis and treatment, including novel antibiotics, antimicrobial implant coatings, and bacteriophage therapy. Due to the costs and risks associated with clinical trials, effective preclinical screening is essential.
Aim: To test the efficacy of these new therapies, we aim to develop a reliable and economical preclinical model of bone infection in mice. A relevant model would feature a local long bone defect seeded with a pathogenic microorganism associated with orthopaedic infection.
Methods: Tibial drilled-hole surgeries were conducted in the tibiae of C57BL/6 mice (N=100) with the introduction of Staphylococcus aureus (ATCC-12600). Variables included drilled-hole position, route of inoculation, and presence of a metal pin to act as a biofilm surface. In a variant of the surgery, a needle was used to create the initial hole. Animals were monitored for physiological or radiographic evidence of infection without prophylactic antibiotics. At the endpoint, blood, bone swabs, soft-tissue biopsies and pins were taken for bacterial culture. X-ray and micro-CT scans were performed along with histology analysis.
Results: The presence of an implant was found to be essential for reliable infection (80-100% infection rate), suggesting that formation of a local biofilm is critical for infection at low doses of S. aureus inoculation. Midshaft drilled-holes led to the frequent fracture of the tibiae, making this an unfavourable model in terms of biomechanical strength. Endpoint analyses showed a lack of sepsis despite the detection of bacteria within the local site. Micro-CT and X-ray imaging were found to be advantageous when used in concert to visualise osteolysis at the infected defect.
Conclusions: These studies indicate the nuance and complexity associated with model development but confirm the mouse can be a useful model organism for orthopaedic infection. Future work will employ bioluminescent bacterial strains that enable detection of infection progress in real-time.