title: A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA. Electronic address: jessica-goetz@uiowa.edu.
authors.forename: J E
authors.initials: JE
authors.lastname: Goetz
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Fredericks
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Petersen
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Rudert
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Baer
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Swanson
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Roberts
authors.affiliation: Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Orthopaedics, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tochigi
mesh_terms: D000818:Animals; D016512:Ankle Injuries / Q000150:complications* / Q000473:pathology / Q000601:surgery; D000843:Ankle Joint / Q000473:pathology*; D004195:Disease Models, Animal; D005593:Fracture Fixation, Internal; D057072:Intra-Articular Fractures / Q000150:complications* / Q000473:pathology / Q000601:surgery; D008297:Male; D010003:Osteoarthritis / Q000209:etiology* / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D013978:Tibial Fractures / Q000150:complications* / Q000473:pathology / Q000601:surgery
keywords: Closed fracture; Intra-articular fracture; Post-traumatic osteoarthritis; Yucatan minipig