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Original Investigation |

Defining the Critical-Sized Defect in a Rat Segmental Mandibulectomy Model

Adam S. DeConde, MD1; Matthew K. Lee, MD1; Douglas Sidell, MD1; Tara Aghaloo, DDS, MD, PhD2,3,4; Min Lee, PhD2,5; Sotirios Tetradis, DDS, PhD2,3; Kyle Low, BA6; David Elashoff, PhD4,7; Tristan Grogan, MS7; Ali R. Sepahdari, MD8; Maie St John, MD, PhD1,2
[+] Author Affiliations
1Department of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA)
2Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA
3Division of Oral Radiology, School of Dentistry, UCLA
4Division of Diagnostic and Surgical Sciences, School of Dentistry, UCLA
5Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, School of Dentistry, UCLA
6currently a postbaccalaureate student at School of Dentistry, UCLA
7Department of Medicine Statistics Core, David Geffen School of Medicine, UCLA
8Department of Radiology, David Geffen School of Medicine, UCLA
JAMA Otolaryngol Head Neck Surg. 2014;140(1):58-65. doi:10.1001/jamaoto.2013.5669.
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Importance  Advances in tissue engineering offer potential alternatives to current mandibular reconstructive techniques; however, before clinical translation of this technology, a relevant animal model must be used to validate possible interventions.

Objective  To establish the critical-sized segmental mandibular defect that does not heal spontaneously in the rat mandible.

Design and Setting  Prospective study of mandibular defect healing in 29 Sprague-Dawley rats in an animal laboratory.

Interventions  The rats underwent creation of 1 of 4 segmental mandibular defects measuring 0, 1, 3, and 5 mm. All mandibular wounds were internally fixated with 1-mm microplates and screws and allowed to heal for 12 weeks, after which the animals were killed humanely.

Main Outcomes and Measures  Analysis with micro–computed tomography of bony union and formation graded on semiquantitative scales.

Results  Seven animals were included in each experimental group. No 5-mm segmental defects successfully developed bony union, whereas all 0- and 1-mm defects had continuous bony growth across the original defect on micro–computed tomography. Three of the 3-mm defects had bony continuity, and 3 had no healing of the bony wound. Bone union scores were significantly lower for the 5-mm defects compared with the 0-, 1-, and 3-mm defects (P < .01).

Conclusions and Relevance  The rat segmental mandible model cannot heal a 5-mm segmental mandibular defect. Successful healing of 0-, 1-, and 3-mm defects confirms adequate stabilization of bony wounds with internal fixation with 1-mm microplates. The rat segmental mandibular critical-sized defect provides a clinically relevant testing ground for translatable mandibular tissue engineering efforts.

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Figures

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Figure 1.
Segmental Defect Locations

Location of the segmental mandibular defects on an explanted mandible on the buccal (A) and lingual (B) surfaces.

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Figure 2.
Defect Plating Pattern

Plating patterns used for the 0- and 1-mm (A), 3-mm (B), and 5-mm (C) defects.

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Figure 3.
Intraoperative Rigid Fixation

Intraoperative view of a 5-mm defect stabilized with internal fixation.

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Figure 4.
Bone Union Scores

Scores are described in the Micro-CT (micro–computed tomography) Analysis subsection of the Methods section. Error bars indicate 95% confidence intervals. For pairwise relationships on Mann-Whitney testing, P < .05 (0 vs 3 mm, 0 vs 5 mm, 1 vs 3 mm, 1 vs 5 mm, and 3 vs 5 mm).aAll rats with 5-mm defects received a mean bone union score of 0.

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Figure 5.
Bone Formation Scores

Scores are described in the Micro-CT (micro–computed tomography) Analysis subsection of the Methods section. Error bars indicate 95% confidence intervals. For pairwise relationships on Mann-Whitney testing, P < .05 (0 vs 3 mm, 0 vs 5 mm, 1 vs 3 mm, 1 vs 5 mm, and 3 vs 5 mm).

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Figure 6.
Micro–Computed Tomography Reconstructions

Three-dimensional reconstructions of representative segmental defects from each group are depicted.

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