Gu Cheng1, Zhi Li1, Qilong Wan1, Kun Lv1, Dianqi Li1, Xin Xing1, Zubing Li2. 1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, PR China; Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Wuhan University, Wuhan, PR China. 2. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, PR China; Department of Oral and Maxillofacial Surgery, College and Hospital of Stomatology, Wuhan University, Wuhan, PR China. Electronic address: lizubing@sina.com.
Abstract
BACKGROUND: It has traditionally been difficult to create full-thickness defects in the mandibles of rodent animals because of dissimilar anatomic structures with humans, interference from teeth of jaws, and limited surgical access. To better mimic the cellular situation and the unique masticatory stresses in maxillofacial regions of humans, we developed an animal model of mandibular defects, in which rabbits were implanted with the beta-tricalcium phosphate/chitosan (β-TCP/CS) scaffolds after a dental extraction and the creation of a full-thickness bone defect. METHODS: Seventy-two New Zealand rabbits underwent unilateral mandibular defect surgery in the premolar region and were randomly divided into three groups as follows: (1) The full-thickness bicortical defect with tooth extraction of the mandibular first premolar and implantation of bone marrow stromal cells/β-TCP/CS scaffold graft (group G + E); (2) the bicortical defect, not treated with tooth extraction and implanted with the bone marrow stromal cells/β-TCP/CS grafts (group G); and (3) the bicortical defects created in the same location in the negative control group, not treated with tooth extraction and graft implantation (group C). The defects in all groups were examined at 4 and 12 wk using mechanical tests, x-ray, and histology observation to determine the biomechanical stability, quantity, and quality of the newly formed bone. RESULTS: Group G + E displayed the largest amount of new bone formation, with high mechanical forces in compression and three-point bending tests, filled in the mandibular defects at 4 wk, and complete reconstruction of bony contours and bridging by 12 wk after implantation. Although similar mechanical forces and new bone formation were demonstrated by the normal healing specimens, the abnormal cases with periapical diseases of group G demonstrated less amount of new bone formation and smaller mechanical forces when compared with those of group G + E at 4 and 12 wk. In contrast, the defect without graft implantation in the negative control group (group C) failed to bridge itself and displayed fibrous tissue filled in the defects with the lowest mechanical forces at both 4 and 12 wk of implantation. CONCLUSIONS: A 10-mm diameter, full-thickness mandibular defect treated with tooth extraction of the first mandibular premolar can mimic the segmental jawbone defects and fulfill the requirements of a critical-size mandibular defect in rabbits. Furthermore, the new bone regeneration and biomechanical stability of the mandible can be promoted by extraction of the teeth located in the defect side, which demonstrated the potential of this model as a test bed for tissue-engineering grafts used in jawbone defects.
BACKGROUND: It has traditionally been difficult to create full-thickness defects in the mandibles of rodent animals because of dissimilar anatomic structures with humans, interference from teeth of jaws, and limited surgical access. To better mimic the cellular situation and the unique masticatory stresses in maxillofacial regions of humans, we developed an animal model of mandibular defects, in which rabbits were implanted with the beta-tricalcium phosphate/chitosan (β-TCP/CS) scaffolds after a dental extraction and the creation of a full-thickness bone defect. METHODS: Seventy-two New Zealand rabbits underwent unilateral mandibular defect surgery in the premolar region and were randomly divided into three groups as follows: (1) The full-thickness bicortical defect with tooth extraction of the mandibular first premolar and implantation of bone marrow stromal cells/β-TCP/CS scaffold graft (group G + E); (2) the bicortical defect, not treated with tooth extraction and implanted with the bone marrow stromal cells/β-TCP/CS grafts (group G); and (3) the bicortical defects created in the same location in the negative control group, not treated with tooth extraction and graft implantation (group C). The defects in all groups were examined at 4 and 12 wk using mechanical tests, x-ray, and histology observation to determine the biomechanical stability, quantity, and quality of the newly formed bone. RESULTS: Group G + E displayed the largest amount of new bone formation, with high mechanical forces in compression and three-point bending tests, filled in the mandibular defects at 4 wk, and complete reconstruction of bony contours and bridging by 12 wk after implantation. Although similar mechanical forces and new bone formation were demonstrated by the normal healing specimens, the abnormal cases with periapical diseases of group G demonstrated less amount of new bone formation and smaller mechanical forces when compared with those of group G + E at 4 and 12 wk. In contrast, the defect without graft implantation in the negative control group (group C) failed to bridge itself and displayed fibrous tissue filled in the defects with the lowest mechanical forces at both 4 and 12 wk of implantation. CONCLUSIONS: A 10-mm diameter, full-thickness mandibular defect treated with tooth extraction of the first mandibular premolar can mimic the segmental jawbone defects and fulfill the requirements of a critical-size mandibular defect in rabbits. Furthermore, the new bone regeneration and biomechanical stability of the mandible can be promoted by extraction of the teeth located in the defect side, which demonstrated the potential of this model as a test bed for tissue-engineering grafts used in jawbone defects.