Establishing a Critical-Size Mandibular Defect Model in Growing Pigs: Characterization of Spontaneous Healing

PurposeA large animal model is desired for preclinical studies aimed at reconstructing severe mandibular skeletal defects using tissue engineering techniques. To identify the size and location requirements for a mandibular critical-size bone defect in growing pigs, the present study investigated the spontaneous healing of surgically created mandibular defects.Materials and MethodsSix 4-month-old domestic pigs were used. In pigs 1 and 2, a 3-, 5-, or 7-cm3 subperiosteal mandibular defect was created. In pigs 3 to 6, 3- to 5-cm3 bilateral defects were randomly created at the anterior (apical to the molars) and posterior (mandibular angle) mandibular regions. Spontaneous healing of these defects was assessed by serial computed tomography scans (postoperative week 1, 6, and 12) and histologic analyses.ResultsIn pigs 1 and 2, regardless of defect size, the anterior, but not posterior, defects had largely healed. Systematic analyses of pigs 3 to 6 revealed, first, the extent of defect regeneration from spontaneous healing was significantly less in the posterior than in the anterior defects, with about two thirds and one third of the original defect volume remaining, respectively. Second, histologically, the posterior defects had considerably less regeneration and more evident tapering of the new bone than did the anterior defects. Finally, the buccal periosteum had completely regenerated in the anterior defects, but had only partially done so in the posterior defects. Also, the buccal surface contour was moderately concave in the anterior defects, but it was severely concave in the posterior defects.ConclusionsDespite robust spontaneous healing of mandibular defects in growing pigs, 5-cm3 defects in the mandibular angle region without buccal periosteum would be a reasonable critical-size defect model relevant to mandibular defects in adolescent humans.