Preparation and properties of a new artificial bone composite material_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

GE Jianhua ¹ , JIA Le ¹ , DUAN Ke ¹ , LI Yang ¹ , MA Yue ¹ , YAN Jiyuan ¹ , DUAN Xin ² ,  WU Guibing ³

1. Department of Bone and Joint Surgery, Affiliated Hospital of Southwest Medical University, Sichuan Provincial Laboratory of Orthopedic Implant Device R&D and Application Technology Engineering, Luzhou Sichuan, 646000, P. R. China;
2. Department of Orthopedics, West China Hospital of Sichuan University, Chengdu Sichuan, 610041, P. R. China;
3. Department of Orthopedics, Hejiang People’s Hospital, Hejiang Sichuan, 646200, P. R. China;

Corresponding author：

WU Guibing, Email: gbingwu78@126.com

Keywords：

Artificial bone composite material; α-calcium sulfate hemihydrate; β-tricalcium phosphate; hyaluronic acid

DOI：

10.7507/1002-1892.202211097

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Objective To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/β-tricalcium phosphate (β-TCP) material (hereinafter referred to as composite material). Methods Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the β-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and β-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ β-TCP composite material. The α-CSH/β-TCP composite material prepared with α-CSH, β-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity. Results The HA/α-CSH/β-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 μm. When the content of β-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/β-TCP proportion (P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration (P<0.05), but it has no obvious effect on the setting time of composite material (P>0.05). The cytotoxicity level of HA/α-CSH/β-TCP composite material ranged from 0 to 1, without cytotoxicity. Conclusion The HA/α-CSH/β-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.

Citation： GE Jianhua, JIA Le, DUAN Ke, LI Yang, MA Yue, YAN Jiyuan, DUAN Xin, WU Guibing. Preparation and properties of a new artificial bone composite material. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(4): 488-494. doi: 10.7507/1002-1892.202211097 Copy

1.	王子瑞, 朱金亮, 何志敏, 等. 人工合成骨修复材料的临床应用及展望. 生物骨科材料与临床研究, 2021, 18(4): 8-17.
2.	Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta Biomater, 2020, 113: 23-41.
3.	Chappard D. Beta-tricalcium phosphate and bone surgery: Editorial. Morphologie, 2017, 101(334): 111-112.
4.	Lin J, Xu D, Liu Z, et al. Physicochemical and biological properties of carboxymethyl chitosan zinc (CMCS-Zn)/α-calcium sulfate hemihydrate (α-CSH) composites. Mater Sci Eng C Mater Biol Appl, 2021, 131: 112496. doi: 10.1016/j.msec.2021.112496.
5.	Ren M, Wang X, Hu M, et al. Enhanced bone formation in rat critical-size tibia defect by a novel quercetin-containing alpha-calcium sulphate hemihydrate/nano-hydroxyapatite composite. Biomed Pharmacother, 2022, 146: 112570. doi: 10.1016/j.biopha.2021.112570..
6.	Khairoun I, Driessens FC, Boltong MG, et al. Addition of cohesion promotors to calcium phosphate cements. Biomaterials, 1999, 20(4): 393-398.
7.	USP ⅩⅫ-NF ⅩⅦ. Toxicity classification in US Pharmacopeia. Rockville: United States harmacopeial Convention Inc., 1990: 2069.
8.	Wei S, Ma JX, Xu L, et al. Biodegradable materials for bone defect repair. Mil Med Res, 2020, 7(1): 54. doi: 10.1186/s40779-020-00280-6.
9.	Xue N, Ding XF, Huang RZ, et al. Bone tissue engineering in the treatment of bone defects. Pharmaceuticals (Basel), 2022, 15(7): 879. doi: 10.3390/ph15070879.
10.	魏晨旭, 何怡文, 王聃, 等. 组织工程学中骨修复材料的研究热点与进展. 中国组织工程研究, 2020, 24(10): 1615-1621.
11.	徐睿. 硫酸钙基骨修复材料的性能改进与研究. 太原: 太原理工大学, 2020.
12.	Miao M, Xin F, Wang G, et al. Direct transformation of FGD gypsum to calcium sulfate hemihydrate whiskers: Preparation, simulations, and process analysis. Particuology, 2015, 19(4): 53-59.
13.	Mao K, Cui F, Li J, et al. Preparation of combined β-TCP/α-CSH artificial bone graft and its performance in a spinal fusion model. J Biomater Appl, 2012, 27(1): 37-45.
14.	李鹏, 毛克亚, 江涛, 等. β-磷酸三钙/α-半水硫酸钙复合人工骨体外降解速度可与成骨一致. 中国组织工程研究与临床康复, 2011, 15(51): 9501-9504.
15.	杜明奎, 毛克亚, 王继芳. β-磷酸三钙与α-半水硫酸钙降解研究进展. 国际骨科学杂志, 2008, 29(1): 6-7, 25.
16.	Tao SC, Li XR, Wei WJ, et al. Polymeric coating on β-TCP scaffolds provides immobilization of small extracellular vesicles with surface-functionalization and ZEB1-Loading for bone defect repair in diabetes mellitus. Biomaterials, 2022, 283: 121465. doi: 10.1016/j.biomaterials.2022.121465.
17.	桑宏勋, 王臻, 郭征, 等. 多孔TCP人工骨修复肿瘤性骨缺损的临床效果与骨愈合机制探讨. 中国修复重建外科杂志, 2008, 22(4): 463-467.
18.	Petta D, Fussell G, Hughes L, et al. Calcium phosphate/thermoresponsive hyaluronan hydrogel composite delivering hydrophilic and hydrophobic drugs. J Orthop Translat, 2015, 5: 57-68.
19.	Qiu Y, Ma Y, Huang Y, et al. Current advances in the biosynthesis of hyaluronic acid with variable molecular weights. Carbohydr Polym, 2021, 269: 118320. doi: 10.1016/j.carbpol.2021.118320.
20.	Pereira H, Sousa DA, Cunha A, et al. Hyaluronic Acid. Adv Exp Med Biol, 2018, 1059: 137-153.
21.	梁茂华. β-TCP/α-CSH复合人工骨的制备及在脊柱融合模型中的应用. 北京: 中国人民解放军军医进修学院, 2008.
22.	Wei Y, Chang YH, Liu CJ, et al. Integrated oxidized-hyaluronic acid/collagen hydrogel with β-TCP using proanthocyanidins as a crosslinker for drug delivery. Pharmaceutics, 2018, 10(2): 37. doi: 10.3390/pharmaceutics10020037.
23.	冯琦. 明胶/透明质酸微凝胶组装体的构建及其在关节软骨再生修复中的应用研究. 广州: 华南理工大学, 2021.
24.	叶海民, 丁凌华, 孔维豪, 等. 多级微管结构骨支架载体促进成骨成血管作用及机制. 中国组织工程研究, 2021, 25(4): 621-625.
25.	Gerhardt LC, Boccaccini AR. Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials (Basel), 2010, 3(7): 3867-3910.
26.	张钟毓, 许燕, 张旭婧, 等. 同轴骨组织工程支架降解特性研究. 机械设计与制造, 2021, (2): 5-9.

1. 王子瑞, 朱金亮, 何志敏, 等. 人工合成骨修复材料的临床应用及展望. 生物骨科材料与临床研究, 2021, 18(4): 8-17.
2. Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta Biomater, 2020, 113: 23-41.
3. Chappard D. Beta-tricalcium phosphate and bone surgery: Editorial. Morphologie, 2017, 101(334): 111-112.
4. Lin J, Xu D, Liu Z, et al. Physicochemical and biological properties of carboxymethyl chitosan zinc (CMCS-Zn)/α-calcium sulfate hemihydrate (α-CSH) composites. Mater Sci Eng C Mater Biol Appl, 2021, 131: 112496. doi: 10.1016/j.msec.2021.112496.
5. Ren M, Wang X, Hu M, et al. Enhanced bone formation in rat critical-size tibia defect by a novel quercetin-containing alpha-calcium sulphate hemihydrate/nano-hydroxyapatite composite. Biomed Pharmacother, 2022, 146: 112570. doi: 10.1016/j.biopha.2021.112570..
6. Khairoun I, Driessens FC, Boltong MG, et al. Addition of cohesion promotors to calcium phosphate cements. Biomaterials, 1999, 20(4): 393-398.
7. USP ⅩⅫ-NF ⅩⅦ. Toxicity classification in US Pharmacopeia. Rockville: United States harmacopeial Convention Inc., 1990: 2069.
8. Wei S, Ma JX, Xu L, et al. Biodegradable materials for bone defect repair. Mil Med Res, 2020, 7(1): 54. doi: 10.1186/s40779-020-00280-6.
9. Xue N, Ding XF, Huang RZ, et al. Bone tissue engineering in the treatment of bone defects. Pharmaceuticals (Basel), 2022, 15(7): 879. doi: 10.3390/ph15070879.
10. 魏晨旭, 何怡文, 王聃, 等. 组织工程学中骨修复材料的研究热点与进展. 中国组织工程研究, 2020, 24(10): 1615-1621.
11. 徐睿. 硫酸钙基骨修复材料的性能改进与研究. 太原: 太原理工大学, 2020.
12. Miao M, Xin F, Wang G, et al. Direct transformation of FGD gypsum to calcium sulfate hemihydrate whiskers: Preparation, simulations, and process analysis. Particuology, 2015, 19(4): 53-59.
13. Mao K, Cui F, Li J, et al. Preparation of combined β-TCP/α-CSH artificial bone graft and its performance in a spinal fusion model. J Biomater Appl, 2012, 27(1): 37-45.
14. 李鹏, 毛克亚, 江涛, 等. β-磷酸三钙/α-半水硫酸钙复合人工骨体外降解速度可与成骨一致. 中国组织工程研究与临床康复, 2011, 15(51): 9501-9504.
15. 杜明奎, 毛克亚, 王继芳. β-磷酸三钙与α-半水硫酸钙降解研究进展. 国际骨科学杂志, 2008, 29(1): 6-7, 25.
16. Tao SC, Li XR, Wei WJ, et al. Polymeric coating on β-TCP scaffolds provides immobilization of small extracellular vesicles with surface-functionalization and ZEB1-Loading for bone defect repair in diabetes mellitus. Biomaterials, 2022, 283: 121465. doi: 10.1016/j.biomaterials.2022.121465.
17. 桑宏勋, 王臻, 郭征, 等. 多孔TCP人工骨修复肿瘤性骨缺损的临床效果与骨愈合机制探讨. 中国修复重建外科杂志, 2008, 22(4): 463-467.
18. Petta D, Fussell G, Hughes L, et al. Calcium phosphate/thermoresponsive hyaluronan hydrogel composite delivering hydrophilic and hydrophobic drugs. J Orthop Translat, 2015, 5: 57-68.
19. Qiu Y, Ma Y, Huang Y, et al. Current advances in the biosynthesis of hyaluronic acid with variable molecular weights. Carbohydr Polym, 2021, 269: 118320. doi: 10.1016/j.carbpol.2021.118320.
20. Pereira H, Sousa DA, Cunha A, et al. Hyaluronic Acid. Adv Exp Med Biol, 2018, 1059: 137-153.
21. 梁茂华. β-TCP/α-CSH复合人工骨的制备及在脊柱融合模型中的应用. 北京: 中国人民解放军军医进修学院, 2008.
22. Wei Y, Chang YH, Liu CJ, et al. Integrated oxidized-hyaluronic acid/collagen hydrogel with β-TCP using proanthocyanidins as a crosslinker for drug delivery. Pharmaceutics, 2018, 10(2): 37. doi: 10.3390/pharmaceutics10020037.
23. 冯琦. 明胶/透明质酸微凝胶组装体的构建及其在关节软骨再生修复中的应用研究. 广州: 华南理工大学, 2021.
24. 叶海民, 丁凌华, 孔维豪, 等. 多级微管结构骨支架载体促进成骨成血管作用及机制. 中国组织工程研究, 2021, 25(4): 621-625.
25. Gerhardt LC, Boccaccini AR. Bioactive glass and glass-ceramic scaffolds for bone tissue engineering. Materials (Basel), 2010, 3(7): 3867-3910.
26. 张钟毓, 许燕, 张旭婧, 等. 同轴骨组织工程支架降解特性研究. 机械设计与制造, 2021, (2): 5-9.

Chinese Journal of Reparative and Reconstructive Surgery

Preparation and properties of a new artificial bone composite material

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