Application of biomimetic mineralized collagen bone graft material in rabbits posterolateral spinal fusion_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

SONG Tianxi ¹ , HU Yanli ¹ , CUI Yun ¹ , HE Zhimin ¹ , ZHU Jinliang ¹ , WANG Xiumei ² ,  QIU Zhiye ^1,2

1. Beijing Allgens Medical Technology Co., Ltd., Beijing, 100176, P.R.China;
2. School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, P.R.China;

Corresponding author：

QIU Zhiye, Email: qiuzy@allgensmed.com

Keywords：

Mineralized collagen; bone marrow; spinal fusion; osteoinductivity; rabbit

DOI：

10.7507/1002-1892.201804119

Video：

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ObjectiveTo investigate the bone repair and regeneration abilities of biomimetic mineralized collagen bone graft material and autologous bone marrow in rabbit posterolateral spinal fusion model.MethodsTwenty-seven 20-week-old male New Zealand white rabbits were used to establish the posterolateral spinal fusion model of L₅ and L₆ segments by stripping the transverse process and exposing cancellous bone with electric burr. The rabbits were randomly divided into 3 groups, 9 in each group. Groups A, B, and C were implanted 1.5 mL autologous iliac bone, 1.5 mL (30 mm×10 mm×5 mm) biomimetic mineralized collagen bone graft material, and 1.5 mL (30 mm×10 mm×5 mm) biomimetic mineralized collagen bone graft material and autologous bone marrow in each bone defect. At 4, 8, and 12 weeks after operation, the apparent hardness of the bone grafting area was observed by manipulation method, in order to evaluate bone graft fusion effects. Three animals were sacrificed in each group at each time point, the vertebral body specimens were excised and the bone defect repair and fusion were observed by X-ray films, and three-dimensional CT examination was performed to evaluate whether new bone was formed in the body. HE staining was performed at each time point to observe the formation of new bone and the repair and fusion of bone defects.ResultsThe manipulation test showed that bone graft fusion was not found in all groups at 4 weeks after operation; 3 (50.0%), 2 (33.3%), and 4 (66.7%) of groups A, B, and C reached bone graft fusion at 8 weeks after operation; 5 (83.3%), 4 (66.7%), and 5 (83.3%) of groups A, B, and C reached bone graft fusion at 12 weeks after operation; the fusion rate of group C was similar to that of group A, and all higher than that of group B. X-ray film observation showed that the fusion rate of group C at 8 and 12 weeks after operation was higher than that of group B, which was similar to group A. Three-dimensional CT observation showed that the degree of bone fusion in group C was better than that in group B, which was close to group A. HE staining observation showed that large area of mature lamellar bone coverage appeared in the bone graft area of groups A, B, and C at 12 weeks after operation, the material was completely degraded, and the marginal boundary of the host bone disappeared and tightly combined.ConclusionBiomimetic mineralized collagen bone graft material mixed with autologous bone marrow has good osteoinduction and osteogenesis guidance. Compared with biomimetic mineralized collagen bone graft material, it has better and faster osteogenesis effect, which is close to autologous bone transplantation.

Citation： SONG Tianxi, HU Yanli, CUI Yun, HE Zhimin, ZHU Jinliang, WANG Xiumei, QIU Zhiye. Application of biomimetic mineralized collagen bone graft material in rabbits posterolateral spinal fusion. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(9): 1137-1143. doi: 10.7507/1002-1892.201804119 Copy

1.	王迎军, 杜昶, 赵娜如, 等. 仿生人工骨修复材料研究. 华南理工大学学报(自然科学版), 2012, 40(10): 51-58.
2.	Cui F Z, Li Y, Ge J. Self-assembly of mineralized collagen composites. Materials Science & Engineering R, 2007, 57(1): 1-27.
3.	Xu SJ, Qiu ZY, Wu JJ, et al. Osteogenic differentiation gene expression profiling of hMSCs on hydroxyapatite and mineralized collagen. Tissue Eng Part A, 2016, 22(1-2): 170-181.
4.	Qiu ZY, Cui Y, Tao CS, et al. Mineralized collagen: rationale, current status, and clinical applications. Materials (Basel), 2015, 8(8): 4733-4750.
5.	Zhang W, Liao SS, Cui FZ. Hierarchical self-assembly of nanofibrils in mineralized collagen. Chem Mater, 2003, 15(16): 3221-3226.
6.	Du C, Cui FZ, Zhang W, et al. Formation of calcium phosphate/collagen composites through mineralization of collagen matrix. J Biomed Mater Res, 2000, 50(4): 518-527.
7.	Boden SD, Schimandle JH, Hutton WC. An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976), 1995, 20(4): 412-420.
8.	Akamaru T, Suh D, Boden SD, et al. Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion. Spine (Phila Pa 1976), 2003, 28(5): 429-434.
9.	Liao SS, Guan K, Cui FZ, et al. Lumbar spinal fusion with a mineralized collagen matrix and rhBMP-2 in a rabbit model. Spine (Phila Pa 1976), 2003, 28(17): 1954-1960.
10.	Walsh WR, Vizesi F, Cornwall GB, et al. Posterolateral spinal fusion in a rabbit model using a collagen-mineral composite bone graft substitute. Eur Spine J, 2009, 18(11): 1610-1620.
11.	Feng L, Zhang L, Cui Y, et al. Clinical evaluations of mineralized collagen in the extraction sites preservation. Regen Biomater, 2016, 3(1): 41-48.
12.	Qiu ZY, Zhang YQ, Zhang ZQ, et al. Biodegradable mineralized collagen plug for the reconstruction of craniotomy burr-holes: A report of three cases. Transl Neurosci Clin, 2015, 1(1): 3-9.
13.	Yu QS, Chen L, Qiu ZY, et al. Skull repair materials applied in cranioplasty: History and progress. Transl Neurosci Clin, 2017, 3(1): 48-57.
14.	Peng C, Wang HP, Yan JH, et al. Locking system strengthened by biomimetic mineralized collagen putty for the treatment of osteoporotic proximal humeral fractures. Regen Biomater, 2017, 4(5): 289-294.
15.	Wang X, Kou JM, Yue Y, et al. Clinical observations of osteoporotic vertebral compression fractures by using mineralized collagen modified polymethylmethacrylate bone cement. Regenerative Biomaterials, 2017, 4(2): 105-109.
16.	Jiang HJ, Xu J, Qiu ZY, et al. Mechanical properties and cytocompatibility improvement of vertebroplasty PMMA bone cements by incorporating mineralized collagen. Materials, 2015, 8(5): 2616-2634.
17.	Wu J, Xu S, Qiu Z, et al. Comparison of human mesenchymal stem cells proliferation and differentiation on poly (methyl methacrylate) bone cements with and without mineralized collagen incorporation. J Biomater Appl, 2016, 30(6): 722-731.
18.	Ghate NS, Cui H. Mineralized collagen artificial bone repair material products used for fusing the podarthral joints with internal fixation-a case report. Regen Biomater, 2017, 4(5): 295-298.
19.	Kou JM, Fu TY, Jia XJ, et al. Clinical observations on repair of non-infected bone nonunion by using mineralized collagen graft. J Biomater Tissue Eng, 2014, 4(12): 1107-1112.
20.	Xia Y, Peng SS, Xie LZ, et al. A novel combination of nano-scaffolds with micro-scaffolds to mimic extracellularmatrices improve osteogenesis. J Biomater Appl, 2014, 29(1): 59-71.
21.	Wang S, Yang YD, Zhao ZJ, et al. Mineralized collagen-based composite bone materials for cranial bone regeneration in developing sheep. ACS Biomater Sci Eng, 2017, 3(6): 1092-1099.
22.	Chen TY, Zhang YQ, Zuo HC, et al. Repairing skull defects in children with nano-hap/collagen composites: A clinical report of thirteen cases. Transl Neurosci Clin, 2016, 2(1): 31-37.

1. 王迎军, 杜昶, 赵娜如, 等. 仿生人工骨修复材料研究. 华南理工大学学报(自然科学版), 2012, 40(10): 51-58.
2. Cui F Z, Li Y, Ge J. Self-assembly of mineralized collagen composites. Materials Science & Engineering R, 2007, 57(1): 1-27.
3. Xu SJ, Qiu ZY, Wu JJ, et al. Osteogenic differentiation gene expression profiling of hMSCs on hydroxyapatite and mineralized collagen. Tissue Eng Part A, 2016, 22(1-2): 170-181.
4. Qiu ZY, Cui Y, Tao CS, et al. Mineralized collagen: rationale, current status, and clinical applications. Materials (Basel), 2015, 8(8): 4733-4750.
5. Zhang W, Liao SS, Cui FZ. Hierarchical self-assembly of nanofibrils in mineralized collagen. Chem Mater, 2003, 15(16): 3221-3226.
6. Du C, Cui FZ, Zhang W, et al. Formation of calcium phosphate/collagen composites through mineralization of collagen matrix. J Biomed Mater Res, 2000, 50(4): 518-527.
7. Boden SD, Schimandle JH, Hutton WC. An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976), 1995, 20(4): 412-420.
8. Akamaru T, Suh D, Boden SD, et al. Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion. Spine (Phila Pa 1976), 2003, 28(5): 429-434.
9. Liao SS, Guan K, Cui FZ, et al. Lumbar spinal fusion with a mineralized collagen matrix and rhBMP-2 in a rabbit model. Spine (Phila Pa 1976), 2003, 28(17): 1954-1960.
10. Walsh WR, Vizesi F, Cornwall GB, et al. Posterolateral spinal fusion in a rabbit model using a collagen-mineral composite bone graft substitute. Eur Spine J, 2009, 18(11): 1610-1620.
11. Feng L, Zhang L, Cui Y, et al. Clinical evaluations of mineralized collagen in the extraction sites preservation. Regen Biomater, 2016, 3(1): 41-48.
12. Qiu ZY, Zhang YQ, Zhang ZQ, et al. Biodegradable mineralized collagen plug for the reconstruction of craniotomy burr-holes: A report of three cases. Transl Neurosci Clin, 2015, 1(1): 3-9.
13. Yu QS, Chen L, Qiu ZY, et al. Skull repair materials applied in cranioplasty: History and progress. Transl Neurosci Clin, 2017, 3(1): 48-57.
14. Peng C, Wang HP, Yan JH, et al. Locking system strengthened by biomimetic mineralized collagen putty for the treatment of osteoporotic proximal humeral fractures. Regen Biomater, 2017, 4(5): 289-294.
15. Wang X, Kou JM, Yue Y, et al. Clinical observations of osteoporotic vertebral compression fractures by using mineralized collagen modified polymethylmethacrylate bone cement. Regenerative Biomaterials, 2017, 4(2): 105-109.
16. Jiang HJ, Xu J, Qiu ZY, et al. Mechanical properties and cytocompatibility improvement of vertebroplasty PMMA bone cements by incorporating mineralized collagen. Materials, 2015, 8(5): 2616-2634.
17. Wu J, Xu S, Qiu Z, et al. Comparison of human mesenchymal stem cells proliferation and differentiation on poly (methyl methacrylate) bone cements with and without mineralized collagen incorporation. J Biomater Appl, 2016, 30(6): 722-731.
18. Ghate NS, Cui H. Mineralized collagen artificial bone repair material products used for fusing the podarthral joints with internal fixation-a case report. Regen Biomater, 2017, 4(5): 295-298.
19. Kou JM, Fu TY, Jia XJ, et al. Clinical observations on repair of non-infected bone nonunion by using mineralized collagen graft. J Biomater Tissue Eng, 2014, 4(12): 1107-1112.
20. Xia Y, Peng SS, Xie LZ, et al. A novel combination of nano-scaffolds with micro-scaffolds to mimic extracellularmatrices improve osteogenesis. J Biomater Appl, 2014, 29(1): 59-71.
21. Wang S, Yang YD, Zhao ZJ, et al. Mineralized collagen-based composite bone materials for cranial bone regeneration in developing sheep. ACS Biomater Sci Eng, 2017, 3(6): 1092-1099.
22. Chen TY, Zhang YQ, Zuo HC, et al. Repairing skull defects in children with nano-hap/collagen composites: A clinical report of thirteen cases. Transl Neurosci Clin, 2016, 2(1): 31-37.

Chinese Journal of Reparative and Reconstructive Surgery

Application of biomimetic mineralized collagen bone graft material in rabbits posterolateral spinal fusion

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