Study on the bone regeneration induced by advanced-platelet-rich fibrin and β- tricalcium phosphate composite_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Xuemei ¹ , ZHANG Yushi ^1,2 ,  ZHONG Ke ¹ , LU Shuai ³ , CHEN Yue ⁴

1. School of Stomatology, Southwest Medical University, Luzhou Sichuan, 646000, P.R.China;
2. Department of Stomatology, Chengdu Hospital of Sichuan Petroleum Administration, Chengdu Sichuan, 610051, P.R.China;
3. Department of Stomatology, Authority Hospital of Chengdu Military Region, Chengdu Sichuan, 610031, P.R.China;
4. Department of Nuclear Medicine & Sichuan Key Laboratory of Nuclear Medicine and Molecular Imaging, Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China;

Corresponding author：

ZHONG Ke, Email: 37435387@qq.com

Keywords：

Advanced-platelet-rich fibrin; β-tricalcium phosphate; Micro-CT; biomechanics; rabbit

DOI：

10.7507/1002-1892.201807002

Video：

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Objective To explore the osteogenesis effect of advanced-platelet-rich fibrin (A-PRF) and β-tricalcium phosphate (β-TCP) composite. Methods Thirty-two healthy female New Zealand rabbits were randomly selected. A-PRF was prepared by collecting blood from middle auricular artery. Rabbits were randomly divided into 6 groups: groups A, B, C, D, and E (6 rabbits in each group) and group F (2 rabbits). Bone defects (6 mm in diameter, 8 mm in depth) were drilled into femur condyle of each rabbit’s both back legs. Then A-PRF and β-TCP composites manufactured by different proportion were planted into bone defects of group A (1∶1), group B (2∶1), group C (4∶1), group D (1∶2) and group E (1∶4) (V/V). The bone defect was not repaired in group F. The specimens were collected at 8 and at 12 weeks after operation. Then gross observation, X-ray examination, Micro-CT examination, and biomechanical test were performed. The bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp), compressive strength, and modulus of elasticity were calculated. Results The gross observation and X-ray examination showed that the osteogenesis effect at 12 weeks was better than that at 8 weeks. At the same time point, the repair of bone defect and the formation of new bone in group B were better than those in other groups. Micro-CT examination showed that the trabeculae of new bone in group B were the most and the trabeculae arranged closely at 8 and 12 weeks. Besides there were significant differences in BV/TV, Tb.N, and Tb.Sp between group B and the other groups (P<0.05). There were significant differences in Tb.N and Tb.Th in group B, BV/TV and Tb.Sp in group C, Tb.Sp in group D between 8 weeks and 12 weeks (P<0.05). Biomechanical tests showed that the compression strength and elastic modulus of group B were the highest, and the compression strength and elastic modulus of group C were the lowest at 8 and at 12 weeks, showing significant differences (P<0.05). There were significant differences in compression strength and elastic modulus of each group between 8 weeks and 12 weeks (P<0.05). Conclusion The A-PRF and β-TCP composite can repair femoral condylar defects in rabbits, and the osteogenesis is better in proportion of 2∶1.

Citation： LI Xuemei, ZHANG Yushi, ZHONG Ke, LU Shuai, CHEN Yue. Study on the bone regeneration induced by advanced-platelet-rich fibrin and β- tricalcium phosphate composite. Chinese Journal of Reparative and Reconstructive Surgery, 2019, 33(2): 177-184. doi: 10.7507/1002-1892.201807002 Copy

1.	Dohan Ehrenfest DM, de Peppo GM, Doglioli P, et al. Slow release of growth factors and thrombospondin-1 in Choukroun’s platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors, 2009, 27(1): 63-69.
2.	Ghanaati S, Booms P, Orlowska A, et al. Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol, 2014, 40(6): 679-689.
3.	Kim TH, Kim SH, Sándor GK, et al. Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing. Arch Oral Biol, 2014, 59(5): 550-558.
4.	Kobayashi E, Flückiger L, Fujioka-Kobayashi M, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig, 2016, 20(9): 2353-2360.
5.	Siddiqui ZR, Jhingran R, Bains VK, et al. Comparative evaluation of platelet-rich fibrin versus beta-tri-calcium phosphate in the treatment of Grade II mandibular furcation defects using cone-beam computed tomography. Eur J Dent, 2016, 10(4): 496-506.
6.	Yilmaz D, Dogan N, Ozkan A, et al. Effect of platelet rich fibrin and beta tricalcium phosphate on bone healing. A histological study in pigs. Acta Cir Bras, 2014, 29(1): 59-65.
7.	毛俊丽, 孙勇, 赵峰, 等. 兔 PRF、A-PRF 制备方法的筛选. 西南国防医药, 2016, 26(6): 593-596.
8.	Schmitz JP, Schwartz Z, Hollinger JO, et al. Characterization of rat calvarial nonunion defects. Acta Anat (Basel), 1990, 138(3): 185-192.
9.	Betti LV, Bramante CM, Cestari TM, et al. Repair of rabbit femur defects with organic bovine bone cancellous block or cortical granules. Int J Oral Maxillofac Implants, 2011, 26(6): 1167-1175.
10.	Gil-Albarova J, Vila M, Badiola-Vargas J, et al. In vivo osteointegration of three-dimensional crosslinked gelatin-coated hydroxyapatite foams. Acta Biomater, 2012, 8(10): 3777-3783.
11.	Zheng H, Bai Y, Shih MS, et al. Effect of a β-TCP collagen composite bone substitute on healing of drilled bone voids in the distal femoral condyle of rabbits. J Biomed Mater Res B Appl Biomater, 2014, 102(2): 376-383.
12.	Liu J, Mao K, Liu Z, et al. Injectable biocomposites for bone healing in rabbit femoral condyle defects. PLoS One, 2013, 8(10): e75668.
13.	王军琳, 朱皓东, 马许宁, 等. 整体填充和颗粒填充 β-TCP 植骨材料对修复腔隙性骨缺损的影响. 现代生物医学进展, 2013, 13(9): 1648-1650.
14.	于威, 李建军. 去抗原牛松质骨支架复合骨形态发生蛋白 2 基因在骨缺损修复过程中的血管化反应. 中国组织工程研究与临床康复, 2008, 12(23): 4559-4562.
15.	殷建, 王斌, 朱超, 等. 局部注射促血管生成素2调控自噬促进体内组织工程人工骨早期血管化和骨缺损修复的研究. 中国修复重建外科杂志, 2018, 32(9): 1150-1156.
16.	Gruber R, Varga F, Fischer MB, et al. Platelets stimulate proliferation of bone cells: in volvement of platelet-derived growth factor, microparticles and membranes. Clin Oral Implants Res, 2002, 13(5): 529-535.
17.	Fujioka-Kobayashi M, Ota MS, Shimoda A, et al. Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering. Biomaterials, 2012, 33(30): 7613-7620.
18.	刘鹏鹤, 代志鹏, 赵甲军, 等. 自体血纤维蛋白凝块对前交叉韧带重建术后腱-骨愈合影响的临床研究. 中国修复重建外科杂志, 2017, 31(7): 799-804.
19.	Will J, Melcher R, Treul C, et al. Porous ceramic bone scaffolds for vascularized bone tissue regeneration. J Mater Sci Mater Med, 2008, 19(8): 2781-2790.
20.	Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26(27): 5474-5491.
21.	Amini AR, Adams DJ, Laurencin CT, et al. Optimally porous and biomechanically compatible scaffolds for large-area bone regeneration. Tissue Eng Part A, 2012, 18(13-14): 1376-1388.
22.	Samavedi S, Whittington AR, Goldstein AS. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater, 2013, 9(9): 8037-8045.
23.	Denry I, Kuhn LT. Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering. Dent Mater, 2016, 32(1): 43-53.
24.	Li J, Baker BA, Mou X, et al. Biopolymer/Calcium phosphate scaffolds for bone tissue engineering. Adv Healthc Mater, 2014, 3(4): 469-484.
25.	何婷婷. 两种富血小板纤维蛋白的降解特性研究. 泸州: 西南医科大学, 2017.

1. Dohan Ehrenfest DM, de Peppo GM, Doglioli P, et al. Slow release of growth factors and thrombospondin-1 in Choukroun’s platelet-rich fibrin (PRF): a gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors, 2009, 27(1): 63-69.
2. Ghanaati S, Booms P, Orlowska A, et al. Advanced platelet-rich fibrin: a new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol, 2014, 40(6): 679-689.
3. Kim TH, Kim SH, Sándor GK, et al. Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing. Arch Oral Biol, 2014, 59(5): 550-558.
4. Kobayashi E, Flückiger L, Fujioka-Kobayashi M, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig, 2016, 20(9): 2353-2360.
5. Siddiqui ZR, Jhingran R, Bains VK, et al. Comparative evaluation of platelet-rich fibrin versus beta-tri-calcium phosphate in the treatment of Grade II mandibular furcation defects using cone-beam computed tomography. Eur J Dent, 2016, 10(4): 496-506.
6. Yilmaz D, Dogan N, Ozkan A, et al. Effect of platelet rich fibrin and beta tricalcium phosphate on bone healing. A histological study in pigs. Acta Cir Bras, 2014, 29(1): 59-65.
7. 毛俊丽, 孙勇, 赵峰, 等. 兔 PRF、A-PRF 制备方法的筛选. 西南国防医药, 2016, 26(6): 593-596.
8. Schmitz JP, Schwartz Z, Hollinger JO, et al. Characterization of rat calvarial nonunion defects. Acta Anat (Basel), 1990, 138(3): 185-192.
9. Betti LV, Bramante CM, Cestari TM, et al. Repair of rabbit femur defects with organic bovine bone cancellous block or cortical granules. Int J Oral Maxillofac Implants, 2011, 26(6): 1167-1175.
10. Gil-Albarova J, Vila M, Badiola-Vargas J, et al. In vivo osteointegration of three-dimensional crosslinked gelatin-coated hydroxyapatite foams. Acta Biomater, 2012, 8(10): 3777-3783.
11. Zheng H, Bai Y, Shih MS, et al. Effect of a β-TCP collagen composite bone substitute on healing of drilled bone voids in the distal femoral condyle of rabbits. J Biomed Mater Res B Appl Biomater, 2014, 102(2): 376-383.
12. Liu J, Mao K, Liu Z, et al. Injectable biocomposites for bone healing in rabbit femoral condyle defects. PLoS One, 2013, 8(10): e75668.
13. 王军琳, 朱皓东, 马许宁, 等. 整体填充和颗粒填充 β-TCP 植骨材料对修复腔隙性骨缺损的影响. 现代生物医学进展, 2013, 13(9): 1648-1650.
14. 于威, 李建军. 去抗原牛松质骨支架复合骨形态发生蛋白 2 基因在骨缺损修复过程中的血管化反应. 中国组织工程研究与临床康复, 2008, 12(23): 4559-4562.
15. 殷建, 王斌, 朱超, 等. 局部注射促血管生成素2调控自噬促进体内组织工程人工骨早期血管化和骨缺损修复的研究. 中国修复重建外科杂志, 2018, 32(9): 1150-1156.
16. Gruber R, Varga F, Fischer MB, et al. Platelets stimulate proliferation of bone cells: in volvement of platelet-derived growth factor, microparticles and membranes. Clin Oral Implants Res, 2002, 13(5): 529-535.
17. Fujioka-Kobayashi M, Ota MS, Shimoda A, et al. Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering. Biomaterials, 2012, 33(30): 7613-7620.
18. 刘鹏鹤, 代志鹏, 赵甲军, 等. 自体血纤维蛋白凝块对前交叉韧带重建术后腱-骨愈合影响的临床研究. 中国修复重建外科杂志, 2017, 31(7): 799-804.
19. Will J, Melcher R, Treul C, et al. Porous ceramic bone scaffolds for vascularized bone tissue regeneration. J Mater Sci Mater Med, 2008, 19(8): 2781-2790.
20. Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26(27): 5474-5491.
21. Amini AR, Adams DJ, Laurencin CT, et al. Optimally porous and biomechanically compatible scaffolds for large-area bone regeneration. Tissue Eng Part A, 2012, 18(13-14): 1376-1388.
22. Samavedi S, Whittington AR, Goldstein AS. Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater, 2013, 9(9): 8037-8045.
23. Denry I, Kuhn LT. Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering. Dent Mater, 2016, 32(1): 43-53.
24. Li J, Baker BA, Mou X, et al. Biopolymer/Calcium phosphate scaffolds for bone tissue engineering. Adv Healthc Mater, 2014, 3(4): 469-484.
25. 何婷婷. 两种富血小板纤维蛋白的降解特性研究. 泸州: 西南医科大学, 2017.

Chinese Journal of Reparative and Reconstructive Surgery

Study on the bone regeneration induced by advanced-platelet-rich fibrin and β- tricalcium phosphate composite

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