Development and Validation of a Preclinical Canine Model for Delayed Onset Fracture-Related Infections

Background: Fracture-Related Infections (FRIs) are a challenging complication in orthopaedics. FRI incidence is considerably high, particularly in open fractures. FRI management typically involves multiple surgical interventions and prolonged antibiotic therapies. This regimen is often ineffective at infection eradication, resulting in poor outcomes and inefficient use of healthcare resources such that improved preventative and therapeutic interventions are needed. To effectively address these gaps, valid preclinical animal models for FRIs are needed. The purpose of this study was to develop and validate a canine ulna model for delayed FRIs that accurately mimics the clinical course noted in patients. Methods: In this model, a distal ulnar ostectomy was established, then internally stabilized with plates and screws that were pre-incubated with methicillin-resistant Staphylococcus aureus. After a 3-week period, all animals underwent irrigation and debridement of the fracture site followed by clinical, radiographic, bacteriologic, and histologic assessments over the subsequent 8 weeks. Results: This preclinical canine model established a valid representation of delayed FRI in patients based on clinical, radiographic, bacteriologic, and histologic features. Bilateral distal ulnar ostectomies stabilized with MRSA-incubated implants were consistently associated with clinical signs of local infection, radiographic evidence for delayed union with osteomyelitis and implant failure, and implant-associated biofilm formation 3 weeks after “fracture” creation. Conclusion: The translational rigor of the model allows for efficient and effective testing of novel preventive and therapeutic interventions aimed at improving outcomes for FRI patients.