Articular fragment restoration is critical to mitigate post-traumatic osteoarthritis in a porcine pilon fracture model

DeKeyser, Graham J.; Epperson, Richard T.; Zhang, Chong; Williams, Dustin L.; Olsen, Aaron L.; Haller, Justin M.

doi:10.1016/j.ocarto.2022.100266

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…However, in addition to the technical difficulties associated with a small animal model including reduction and fixation (as typically follows HELET with IAF in humans), acceptable parameters for articular fracture reduction and hindlimb alignment have not been established in the rat knee. Additionally, while initial high-energy mechanisms of injury and initial fracture severity represent risk factors for PTOA in humans, fracture malreduction with persistent joint incongruity and, in particular for the knee joint, limb malalignment have greater influence on PTOA formation in both humans and large animals [26][27][28][29]. In our model, incongruity and resulting malalignment is simply allowed to persist and thus replicate these risk factors.…”

Section: Discussionmentioning

confidence: 99%

Development and characterization of an intra‐articular fracture mediated model of post‐traumatic osteoarthritis

et al. 2023

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Purpose This study aimed to develop and characterize a closed intra-articular fracture (IAF) mediated post-traumatic osteoarthritis (PTOA) model in rats to serve as a testbed for putative disease modifying interventions. Methods Male rats were subject to a 0 Joule (J), 1 J, 3 J, or 5 J blunt-force impact to the lateral aspect of the knee and allowed to heal for 14 and 56 days. Micro-CT was performed at time of injury and at the specified endpoints to assess bone morphometry and bone mineral density measurements. Cytokines and osteochondral degradation markers were assayed from serum and synovial fluid via immunoassays. Histopathological analyses were performed on decalcified tissues and assessed for evidence of osteochondral degradation. Results High-energy (5 J) blunt impacts consistently induced IAF to the proximal tibia, distal femur, or both while lower energy (1 J and 3 J) impacts did not. CCL2 was found to be elevated in the synovial fluid of rats with IAF at both 14- and 56-days post-injury while COMP and NTX-1 were upregulated chronically relative to sham controls. Histological analysis showed increased immune cell infiltration, increased osteoclasts and osteochondral degradation with IAF relative to sham. Conclusion Based on results from the current study, our data indicates that a 5 J blunt-forced impact adequately and consistently induces hallmark osteoarthritic changes to the articular surface and subchondral bone at 56 days after IAF. Marked development of PTOA pathobiology suggest this model will provide a robust testbed for screening putative disease modifying interventions that might be translated to the clinic for militarily relevant, high-energy joint injuries.

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Section: Discussionmentioning

confidence: 99%

Development and characterization of an intra‐articular fracture mediated model of post‐traumatic osteoarthritis

et al. 2023

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“…3). 31 To get started with animal models for PTOA, it is important to divide steps into 3 phases. First is the feasibility phase, where you must identify a study question and your specific aims, contact an expert on the animal model of interest, engage a local colleague with animal model experience, and finally determine whether you can do this study at your institution.…”

Section: Posttraumatic Oa: Current Models and Translational Relevancementioning

confidence: 99%

Preclinical models of orthopaedic trauma: Orthopaedic Research Society (ORS) and Orthopaedic Trauma Association (OTA) symposium 2022

Wise,

Saiz,

Haller

et al. 2024

OTA International

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Orthopaedic trauma remains a leading cause of patient morbidity, mortality, and global health care burden. Although significant advances have been made in the diagnosis, treatment, and rehabilitation of these injuries, complications such as malunion, nonunion, infection, disuse muscle atrophy and osteopenia, and incomplete return to baseline function still occur. The significant inherent clinical variability in fracture care such as differing patient demographics, injury patterns, and treatment protocols make standardized and replicable study, especially of cellular and molecular based mechanisms, nearly impossible. Hence, the scientists dedicated to improving therapy and treatments for patients with orthopaedic trauma rely on preclinical models. Preclinical models have proven to be invaluable in understanding the timing between implant insertion and bacterial inoculation on the bioburden of infection. Posttraumatic arthritis (PTOA) can take years to develop clinically, but with a porcine pilon fracture model, posttraumatic arthritis can be reliably induced, so different surgical and therapeutic strategies can be tested in prevention. Conversely, the racehorse presents a well-accepted model of naturally occurring PTOA. With preclinical polytrauma models focusing on chest injury, abdominal injury, multiple fractures, and/or head injury, one can study how various injury patterns affect fracture healing can be systemically studied. Finally, these preclinical models serve as a translational bridge to for clinical application in human patients. With selection of the right preclinical model, studies can build a platform to decrease the risk of emerging technologies and provide foundational support for therapeutic clinical trials. In summary, orthopaedic trauma preclinical models allow scientists to simplify a complex clinical challenge, to understand the basic pathways starting with lower vertebrate models. Then, R&D efforts progress to higher vertebrate models to build in more complexity for translation of findings to the clinical practice.

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“…In a recent study of osteochondral defects in a porcine intra-articular pilon fracture model, DeKeyser et al reported significantly worse subchondral bone porosity, increased vascular invasion, and worse OARSI histologic scores in pigs with a defect as compared with anatomically reduced pigs. 19 Tissue engineering may provide a substantial breakthrough in addressing osteochondral defects through 3D-printed scaffolds that can be successfully seeded with mesenchymal stem cells (MSCs) and attached to a bone plug for implantation. Three dimensional printing allows scaffolds to be printed in a variety of shapes to accommodate the bone of interest and minimize point loading at the transition from scaffold to native joint.…”

Section: Preventing Post-traumatic Arthritis In Articular Injuries: T...mentioning

confidence: 99%

Distal femur fractures: basic science and international perspectives

Nauth,

Haller,

Augat

et al. 2024

OTA International

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Distal femur fractures are challenging injuries to manage, and complication rates remain high. This article summarizes the international and basic science perspectives regarding distal femoral fractures that were presented at the 2022 Orthopaedic Trauma Association Annual Meeting. We review a number of critical concepts that can be considered to optimize the treatment of these difficult fractures. These include biomechanical considerations for distal femur fixation constructs, emerging treatments to prevent post-traumatic arthritis, both systemic and local biologic treatments to optimize nonunion management, the relative advantages and disadvantages of plate versus nail versus dual-implant constructs, and finally important factors which determine outcomes. A robust understanding of these principles can significantly improve success rates and minimize complications in the treatment of these challenging injuries.

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Articular fragment restoration is critical to mitigate post-traumatic osteoarthritis in a porcine pilon fracture model

Cited by 4 publications

References 36 publications

Development and characterization of an intra‐articular fracture mediated model of post‐traumatic osteoarthritis

Development and characterization of an intra‐articular fracture mediated model of post‐traumatic osteoarthritis

Preclinical models of orthopaedic trauma: Orthopaedic Research Society (ORS) and Orthopaedic Trauma Association (OTA) symposium 2022

Distal femur fractures: basic science and international perspectives

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