J E Goetz1, D Fredericks2, E Petersen2, M J Rudert2, T Baer2, E Swanson3, N Roberts2, J Martin4, Y Tochigi5. 1. 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. 2. Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA. 3. Department of Bioengineering, University of Washington, Seattle, WA, USA. 4. Department of Orthopaedics & Rehabilitation, University of Iowa, Iowa City, IA, USA; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA. 5. Department of Orthopaedics, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan.
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. DESIGN: 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.
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. DESIGN: 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: Mitchell C Coleman; Jessica E Goetz; Marc J Brouillette; Dongrim Seol; Michael C Willey; Emily B Petersen; Hope D Anderson; Nathan R Hendrickson; Jocelyn Compton; Behnoush Khorsand; Angie S Morris; Aliasger K Salem; Douglas C Fredericks; Todd O McKinley; James A Martin Journal: Sci Transl Med Date: 2018-02-07 Impact factor: 17.956
Authors: Dongrim Seol; Yuki Tochigi; Ashley M Bogner; Ino Song; Douglas C Fredericks; Gail L Kurriger; Sonja M Smith; Jessica E Goetz; Joseph A Buckwalter; James A Martin Journal: J Orthop Res Date: 2018-05-24 Impact factor: 3.494
Authors: Benjamin J Bielajew; Ryan P Donahue; Elliott K Lamkin; Jerry C Hu; Vincent C Hascall; Kyriacos A Athanasiou Journal: Acta Biomater Date: 2022-02-27 Impact factor: 10.633
Authors: James A Martin; Donald D Anderson; Jessica E Goetz; Douglas Fredericks; Douglas R Pedersen; Bruce P Ayati; J Lawrence Marsh; Joseph A Buckwalter Journal: J Orthop Res Date: 2016-08-26 Impact factor: 3.494