J Korean Assoc Oral Maxillofac Surg.  2016 Feb;42(1):20-30. 10.5125/jkaoms.2016.42.1.20.

Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation

• Carlisle P
• Guda T
• Silliman D
• Lien W
• Hale RG
• Brown Baer PR

• KMID: 2189406
• DOI: http://doi.org/10.5125/jkaoms.2016.42.1.20

Abstract

OBJECTIVES
To validate a critical-size mandibular bone defect model in miniature pigs.
MATERIALS AND METHODS
Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks.
RESULTS
In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect.
CONCLUSION
The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

Keyword

Mandible; Autografts; Bone regeneration; Porcine; Critical-size defect

MeSH Terms

Autografts
Bone Regeneration
Bone Remodeling
Dental Implants
Hand
Mandible
Swine*
Dental Implants

Figure

• 

  Fig. 1 A. Schematic diagram of the mandibular bone notch defect study design. B, C. Surgical images of the bilateral bone defects in pigs (n=5). The removed bone (D-F) was morselized, hydrated with sterile saline (G-I) and packed into the left side defect, serving as autograft (J), whereas the right side received no treatment (K); both hemi-mandibles were fixed with plates.

• 

  Fig. 2 Computed tomography (CT) quantification of regenerated bone over the healing time course. A. Using a single slice axial view of the 64-slice CT of the mandible, the bone defect region of interest (outlined by a dotted border) was defined. B. Bone volume/tissue volume (BV/TV) ratio was calculated for all time points in the autograft-treated and untreated sides in each pig (n=5). *Significant differences between weeks at the same time point (P<0.001). **Significant differences between groups at the same time point (P=0.013).

• 

  Fig. 3 Computed tomography quantification of bone superior to the intact mandible over the healing time course. A. The region of interest (outlined by a dashed border) was defined to include the intact bone above the defect (shaded by horizontal lines) and exclude the teeth. Bone volume/tissue volume (BV/TV) ratio (B) and bone mineral density (BMD) (C) was calculated for all time points in the autograft-treated and untreated sides in each pig (n=5). Significant differences indicated by *P=0.013, **P<0.001, ***P=0.005.

• 

  Fig. 4 Lingual view of three-dimensional reconstructions of hemi-mandibles from 64-slice computed tomography images. Volumetric rendering of mineralized tissue and fixation plates of the autograft-treated (left panels) and untreated (right panels) mandibles from one pig at 0 weeks (pre-surgery), 4 weeks post-surgery and 16 weeks post-surgery to represent the pattern of bone regeneration at each time point.

• 

  Fig. 5 Quantification of bone regeneration by micro-computed tomography (µCT) analysis. A. High resolution µCT was performed postmortem on both the autograft-treated and untreated sides of the mandible for each pig (n=5). A representative axial cross-section (left panels) and sagittal cross-section (right panels) are shown here for both the autograft-treated (upper) and untreated (lower) sides. Guttapercha denotes the defect margins (designated by the two centermost single white dots in the sagittal cross-sections). B. Bone regeneration was quantified and reported as the bone volume/tissue volume (BV/TV) ratio (P=0.46).

• 

  Fig. 6 Histological sections along the sagittal cross-section of the mandible. The autograft-treated (A) and the corresponding untreated (B) mandible after 16 weeks post-surgery from a representative pig are shown. Sections were stained with Sanderson's rapid bone stain and counterstained with van Gieson's picrofuchsin to stain mineralized tissue pink/red and soft tissue blue. Gutta-percha markers identifying the defect margins are also visible (pale peach circles). In both the autograft-treated and untreated sections, the border of the old bone (OB) and the new bone (NB) are visible in the high magnification images (border indicated with the yellow dashed line) and osteoblasts (indicated by arrows) can be seen in the lower panels. Blood vessels (BV) are present in the autograft-treated section.

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