A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis.

<bold>Objective: </bold>Translation of promising treatments for post-traumatic osteoarthritis (PTOA) to patients with intra-articular fracture (IAF) has been limited by the lack of a realistic large animal model. To address this issue we developed a large animal model of IAF in the distal tibia of Yucatan minipigs and documented the natural progression of this injury.<bold>Design: </bold>Twenty-two fractures were treated using open reduction and internal fixation with either an anatomic reduction or an intentional 2-mm step-off. Pre-operatively, and 3 days, 1, 2, 4, 8, and 12 weeks post-operatively, animals were sedated for synovial fluid draws and radiographs. Limb loading was monitored at the same time points using a Tekscan Walkway. Animals were sacrificed at 12 weeks and the limbs were harvested for histological evaluation.<bold>Results: </bold>All animals achieved bony union by 12 weeks, facilitating nearly complete recovery of the initial 60% decrease in limb loading. TNFα, IL1β, IL6, and IL8 concentrations in the fractured limbs were elevated (P < 0.05) at specific times during the 2 weeks after fracture. Histological cartilage degeneration was more severe in the step-off group (0.0001 < P < 0.27 compared to normal) than in the anatomic reconstruction group (0.27 < P < 0.99 compared to normal).<bold>Conclusions: </bold>This model replicated key features of a human IAF, including surgical stabilization, inflammatory responses, and progression to osteoarthritic cartilage degeneration, thereby providing a potentially useful model for translating promising treatment options to clinical practice. [ABSTRACT FROM AUTHOR]