Abstract
Many studies aimed at investigating bone repair have been conducted through animal models in recent years. However, limitations do exist in these models due to varying regeneration potential among different animal species. Even using the same animal, big differences exist in the size of critical size defects (CSD) involving the same region. This study aimed to investigate the standardization of radial bone defect models in rabbits and further establish more reliable CSD data. A total of 40 6-month-old New Zealand white rabbits of clean grade totaling 80 radial bones were prepared for bone defect models, according to the principle of randomization. Five different sizes (1.0, 1.2, 1.4, 1.7 and 2.0 cm) of complete periosteal defects were introduced under anesthesia. At 12 weeks postoperatively, with the gradual increase in defect size, the grades of bone growth were significantly decreased in all 5 groups. X-ray, CT scans and H&E staining of the 1.4, 1.7, and 2.0-cm groups showed lower grades of bone growth than that of the 1.0 and 1.2-cm groups respectively (P < 0.05). Using rabbit radial defect model involving 6-month-old healthy New Zealand white rabbits, this study indicates that in order to be critical sized, defects must be greater than 1.4 cm.
Highlights
Bone defects, especially segmental long-bone defects caused by nonunion, delayed union and other factors are common challenges in orthopedic treatments [1,2,3]
At 12 weeks after surgery, in the 1.0-cm group, bone union was seen in most defective sites
According to ASTM Standard F2721, critical size defects (CSD) models in animal experiments for the tissue engineered constructs are defined as “a defect that will not heal without intervention”
Summary
Especially segmental long-bone defects caused by nonunion, delayed union and other factors are common challenges in orthopedic treatments [1,2,3]. Unless the defect size was extensive, the bone defect will heal spontaneously, requiring no further intervention. Bone tissue engineering is warranted for extensive defects that cannot heal spontaneously. Well-established experimental animal models constitute the basis for the research of bone tissue engineering [4,5,6,7,8]. Many studies aimed at investigating bone repair have been conducted using animal models in recent years. Limitations exist due to varying regeneration potential among different animal species. Even though the same species is used, big differences exist in the size of a critical defect (CSD) involving the same region [5,9]. CSD is defined as the smallest size of the PLOS ONE | DOI:10.1371/journal.pone.0146301. CSD is defined as the smallest size of the PLOS ONE | DOI:10.1371/journal.pone.0146301 January 5, 2016
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