Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering

Abstract

Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used for in vivo evaluation of new treatment modalities based on bone tissue engineering.

Hydrophilic surface of Ti6Al4V‐ELI alloy improves the early bone apposition of sheep tibia

“…Also, 2 weeks prior to the surgery, the animals were transferred from the place of rearing to the research center, for proper acclimatization (Lansdowne et al. ). This contributes to the reduction of pre‐operative stresses in animals.…”

“…In this study, previously to surgical procedures, it was evaluated the health of animals through clinical and laboratory tests, such as complete blood count, chemistry and serological profile or, at least, total plasma protein, and careful examination of body weight. Also, 2 weeks prior to the surgery, the animals were transferred from the place of rearing to the research center, for proper acclimatization (Lansdowne et al 2014). This contributes to the reduction of pre-operative stresses in animals.…”

Injectable mineralized microsphere-loaded composite hydrogels for bone repair in a sheep bone defect model

“…Bilateral critical-sized iliac crest bone defects were surgically created in 12 adult female Swiss Alpine sheep as previously described [22] (Supplementary Figure 1B-I). Animals received preoperative intramuscular antibiotics (naxcel, 2.2 mg/kg) and analgesia (banamine, 1.1 mg/kg) prior to induction of anesthesia.…”

Clinical Application of Macroporous Ceramic to Promote Bone Healing in Veterinary Clinical Cases

“…A critical-sized bone defect (CSBD) is defined as the smallest bone defect that will not heal spontaneously during the lifetime in a particular bone and species of animal [23,25]. In a more detailed description, a CSBD has been referred to as a defect that has less than 10% bony regeneration during the lifetime of the animal or duration of the experiment [26,27].…”

“…Furthermore, CSBD should heal with appropriate treatment, and the autologous cancellous bone grafts are still named as the gold standard or positive control. Any new treatment based on bone tissue engineering should be tested and compared with these two landmarks [25]. Given the clinical targets of such applications (mostly aged or health-impaired patients), animals should be skeletally mature, in order to avoid misleading results deriving from the superior potential of the young animals to regenerate bone defects [23].…”