A COMPARATIVE STUDY ON EFFECT OF DIFFERENT DEFECT DIAMETERS ON HEALING IN MIDDLE 1/3 TIBIA MONOLAYER CORTICAL BONE DEFECT MOUSE MODEL_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Fubing ¹ , XU Yongqing ¹ , PAN Xinghua ² , LI Xia ¹ , LIU Hua ¹ , YANG Duming ¹ , LI Jun ¹ , SHA Yong ¹ , SHI Jian ¹ , ZHAO Wanqiu ¹

1Department of Orthopaedics, Research Institute of Orthopaedic Trauma of Chinese PLA, 2Center for Stem Cell and Organ Engineering, Kunming General Hospital of Chengdu Military Command, Kunming Yunnan, 650032, P.R.China. Corresponding author: XU Yongqing, E-mail: xuyongqingkm@163.net;

Corresponding author：

Keywords：

Tibia Bone defect; Animal model; Mouse

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Objective To compare the effect of different defect diameters on healing in the middle 1/3 tibia monolayer cortical bone defect mouse model so as to establish an animal model for bone tissue engineering study, mechanism study on bone defect repair, and gene therapy research. Methods Ten 8-week-old C57BL/6J mice, weighing (20 ± 2) g, were randomly divided into 2 groups, 5 mice in each group. The middle 1/3 tibiae monolayer cortical bone defect model of 0.8 mm (group A) or 1.0 mm (group B) in diameter was established with burr drill. At 7, 21, and 28 days after modeling, the molybdenum target X-ray radiography was used to observe the defect repair; at 28 days, Micro CT and three-dimensional imaging were used to evaluate bone defect repair, and tibia specimens were harvested for HE staining. Results At 7 days after modeling, tibia fracture occurred in 5 mice in group B, no fracture in group A. X-ray films, Micro CT scan, and HE staining showed bony union in group A at 28 days. The quantitative analysis of trabecular bone by Micro CT showed that trabecular number, connectivity density, and bone volume in group A were significantly greater than those in group B (P lt; 0.05), mean of segmented region—mean 2 was significantly less than that in group B (P lt; 0.05), but no significant difference was found in trabecular separation and trabecular thickness between 2 groups (P gt; 0.05). Conclusion The middle 1/3 tibia monolayer cortical bone defect mouse model of 0.8 mm in diameter is the ideal animal model for study repair mechanism of tibia defect or bone tissue engineering.

Citation： LI Fubing,XU Yongqing,PAN Xinghua,LI Xia,LIU Hua,YANG Duming,LI Jun,SHA Yong,SHI Jian,ZHAO Wanqiu. A COMPARATIVE STUDY ON EFFECT OF DIFFERENT DEFECT DIAMETERS ON HEALING IN MIDDLE 1/3 TIBIA MONOLAYER CORTICAL BONE DEFECT MOUSE MODEL. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(10): 1218-1222. doi: Copy

1.	Masquelet AC, Beque T. The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am, 2010, 41(1): 27-37.
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4.	Meinel L, Fajardo R, Hofmann S, et al. Silk implants for the healing of critical size bone defects. Bone, 2005, 37(5): 688-698.
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6.	Brevi BC, Magri AS, Toma L, et al. Cranioplasty for repair of a large bone defect with autologous and homologous bone in children. J Pediatr Surg, 2010, 45(4): E17-20.
7.	Si HP, Lu ZH, Lin YL, et al. Transfect bone marrow stromal cells with pcDNA3.1-VEGF to construct tissue engineered bone in defect repair. Chin Med J (Engl), 2012, 125(5): 906-911.
8.	李福兵, 杜晓兰, 余瑛, 等. 骨形成蛋白4条件性RNA干扰小鼠的建立. 遗传, 2008, 30(3): 341-346.
9.	李福兵, 赵玲, 鲁秀敏, 等. 成熟成骨细胞中敲除基因fgfr1小鼠的制备. 第三军医大学学报, 2008, 30(4): 280-283.
10.	汤译博, 赵亮, 苏佳灿. 骨折动物模型的研究进展. 中国骨伤, 2011, 24(1): 91-93.
11.	Monfoulet L, Rabier B, Chassande O, et al. Drilled hole defects in mouse femur as models of intramembranous cortical and cancellous bone regeneration. Calcif Tissue Int, 2010, 86(1): 72-81.
12.	Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res, 1986, (205): 299-308.
13.	Gokhale A, Rwigema JC, Epperly MW, et al. Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model. In Vivo, 2010, 24(4): 377-385.
14.	Kim MG, Shin DM, Lee SW. The healing of critical-sized bone defect of rat zygomatic arch with particulate bone graft and bone morphogenetic protein-2. J Plast Reconstr Aesthet Surg, 2010, 63(3): 459-466.
15.	de Girolamo L, Arrigoni E, Stanco D, et al. Role of autologous rabbit adipose-derived stem cells in the early phases of the repairing process of critical bone defects. J Orthop Res, 2011, 29(1): 100-108.
16.	靳慧勇, 侯天勇, 罗飞, 等. 小鼠股骨临界骨缺损模型的构建及评估. 第三军医大学学报, 2011, 33(22): 2331-2334.
17.	Nagashima M, Sakai A, Uchida S, et al. Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur. Bone, 2005, 36(3): 502-511.
18.	Zhao M, Zhou J, Li X, et al. Repair of bone defect with vascularized tissue engineered bone graft seeded with mesenchymal stem cells in rabbits. Microsurgery, 2011, 31(2): 130-137.
19.	Anderson ML, Dhert WJ, de Bruijn JD, et al. Critical size defect in the goat’s os ilium. A model to evaluate bone grafts and substitutes. Clin Orthop Relat Res, 1999, (364): 231-239.
20.	Lian Z, Chuanchang D, Wei L, et al. Enhanced healing of goat femur-defect using BMP7 gene-modified BMSCs and load-bearing tissue-engineered bone. J Orthop Res, 2010, 28(3): 412-418.
21.	Riegger C, Kropil P, Jungbluth P, et al. Quantitative assessment of bone defect healing by multidetector CT in a pig model. Skeletal Radiol, 2012, 41(5): 531-537.
22.	Thoma DS, Halg GA, Dard MM, et al. Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipigs. Clin Oral Implants Res, 2009, 20(1): 7-16.

1. Masquelet AC, Beque T. The concept of induced membrane for reconstruction of long bone defects. Orthop Clin North Am, 2010, 41(1): 27-37.
2. Wiese A, Pape HC. Bone defects caused by high-energy injuries, bone loss, infected nonunions, and nonunions. Orthop Clin North Am, 2010, 41(1): 1-4.
3. Hesse E, Kluge G, Atfi A, et al. Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft. Bone, 2010, 46(5): 1457-1463.
4. Meinel L, Fajardo R, Hofmann S, et al. Silk implants for the healing of critical size bone defects. Bone, 2005, 37(5): 688-698.
5. Van de Watering FC, van den Beucken JJ, Walboomers XF, et al. Calcium phosphate/poly (D, L-lactic-co-glycolic acid) composite bone substitute materials: evaluation of temporal degradation and bone ingrowth in a rat critical-sized cranial defect. Clin Oral Implants Res, 2012, 23(2): 151-159.
6. Brevi BC, Magri AS, Toma L, et al. Cranioplasty for repair of a large bone defect with autologous and homologous bone in children. J Pediatr Surg, 2010, 45(4): E17-20.
7. Si HP, Lu ZH, Lin YL, et al. Transfect bone marrow stromal cells with pcDNA3.1-VEGF to construct tissue engineered bone in defect repair. Chin Med J (Engl), 2012, 125(5): 906-911.
8. 李福兵, 杜晓兰, 余瑛, 等. 骨形成蛋白4条件性RNA干扰小鼠的建立. 遗传, 2008, 30(3): 341-346.
9. 李福兵, 赵玲, 鲁秀敏, 等. 成熟成骨细胞中敲除基因fgfr1小鼠的制备. 第三军医大学学报, 2008, 30(4): 280-283.
10. 汤译博, 赵亮, 苏佳灿. 骨折动物模型的研究进展. 中国骨伤, 2011, 24(1): 91-93.
11. Monfoulet L, Rabier B, Chassande O, et al. Drilled hole defects in mouse femur as models of intramembranous cortical and cancellous bone regeneration. Calcif Tissue Int, 2010, 86(1): 72-81.
12. Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res, 1986, (205): 299-308.
13. Gokhale A, Rwigema JC, Epperly MW, et al. Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model. In Vivo, 2010, 24(4): 377-385.
14. Kim MG, Shin DM, Lee SW. The healing of critical-sized bone defect of rat zygomatic arch with particulate bone graft and bone morphogenetic protein-2. J Plast Reconstr Aesthet Surg, 2010, 63(3): 459-466.
15. de Girolamo L, Arrigoni E, Stanco D, et al. Role of autologous rabbit adipose-derived stem cells in the early phases of the repairing process of critical bone defects. J Orthop Res, 2011, 29(1): 100-108.
16. 靳慧勇, 侯天勇, 罗飞, 等. 小鼠股骨临界骨缺损模型的构建及评估. 第三军医大学学报, 2011, 33(22): 2331-2334.
17. Nagashima M, Sakai A, Uchida S, et al. Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur. Bone, 2005, 36(3): 502-511.
18. Zhao M, Zhou J, Li X, et al. Repair of bone defect with vascularized tissue engineered bone graft seeded with mesenchymal stem cells in rabbits. Microsurgery, 2011, 31(2): 130-137.
19. Anderson ML, Dhert WJ, de Bruijn JD, et al. Critical size defect in the goat’s os ilium. A model to evaluate bone grafts and substitutes. Clin Orthop Relat Res, 1999, (364): 231-239.
20. Lian Z, Chuanchang D, Wei L, et al. Enhanced healing of goat femur-defect using BMP7 gene-modified BMSCs and load-bearing tissue-engineered bone. J Orthop Res, 2010, 28(3): 412-418.
21. Riegger C, Kropil P, Jungbluth P, et al. Quantitative assessment of bone defect healing by multidetector CT in a pig model. Skeletal Radiol, 2012, 41(5): 531-537.
22. Thoma DS, Halg GA, Dard MM, et al. Evaluation of a new biodegradable membrane to prevent gingival ingrowth into mandibular bone defects in minipigs. Clin Oral Implants Res, 2009, 20(1): 7-16.

Chinese Journal of Reparative and Reconstructive Surgery

A COMPARATIVE STUDY ON EFFECT OF DIFFERENT DEFECT DIAMETERS ON HEALING IN MIDDLE 1/3 TIBIA MONOLAYER CORTICAL BONE DEFECT MOUSE MODEL

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