Abstract
Appropriate well-characterized bone defect animal models remain essential for preclinical research. This pilot study demonstrates a relevant animal model for cancellous bone defect healing. Three different defect diameters (8, 11, 14 mm) of fixed depth (25 mm) were compared in both skeletally immature (18-month-old) and aged sheep (5-year-old). In each animal, four defects were surgically created and placed in the cancellous bone of the medial distal femoral and proximal tibial epiphyses bilaterally. Animals were euthanized at 4 weeks post-operatively to assess early healing and any biological response. Defect sites were graded radiographically, and new bone formation quantified using μCT and histomorphometry. Fibrous tissue was found within the central region in most of the defects with woven bone normally forming near the periphery of the defect. Bone volume fraction [bone volume (BV)/TV] significantly decreased with an increasing defect diameter. Actual BV, however, increased with defect diameter. Bone ingrowth was lower for all defect diameters in the aged group. This pilot study proposes that the surgical creation of 11 mm diameter defects in the proximal tibial and distal femoral epiphyses of aged sheep is a suitable large animal model to study early healing of cancellous bone defects. The refined model allows for the placement of four separate bone defects per animal and encourages a reduction in animal numbers required for preclinical research.
Highlights
Bone grafts remain essential for the augmentation and repair of bone defects arising from trauma, resection, non-unions, and osteolysis
No significant effect was detected for the interaction of the animal age and defect diameter on the radiographic grade (p = 0.32), with both age groups having a similar changes in grade with an increasing defect diameter (Figure 1)
AGE An animal’s age generally has an impact on the healing process with the time required for healing largely increasing with age [11] and skeletal maturity [3]. This delay in bone formation may be due to different temporal expression in aged animals, with delayed cellular differentiation and maturation possibly effecting bone formation [12]
Summary
Bone grafts remain essential for the augmentation and repair of bone defects arising from trauma, resection, non-unions, and osteolysis. As the pursuit for alternatives to autograft continues, appropriate, reproducible, and well-characterized animal models remain essential tools for preclinical research. The appropriate use of research animals while maintaining their well-being should remain a priority [1]. This study presents a refined animal bone healing model . Animal models need to satisfy both experimental and clinical goals and should demonstrate relevant and achievable treatment outcomes. Appropriate bone healing models should aim to replicate clinical scenarios in which a realistic healing rate is reproduced in the animal model
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