Diverse biomaterials have been designed to promote bone regeneration, and due to their potential side effects of adverse inflammation and immune responses, only a few synthetic biomaterials displayed successful clinical outcomes in repairing bone defects. The repair of bone defects remains a big challenge for orthopedists. This study was dedicated to the synthesis of copper-doped octacalcium phosphate powder Cu-OCP with good bone repair potential, which provides a new way for the construction of bone regeneration biomaterials. Five kinds of copper-doped powders, OCP, 0.1Cu-OCP, 0.5Cu-OCP, Cu-OCP and 5Cu-OCP, were synthesized by chemical homogeneous precipitation method. The phases of the powders were analyzed by X-ray diffraction (XRD). The elemental compositions of the powders were analyzed by X-ray fluorescence spectrometer (XRF). The microstructures of the powders were observed by scanning electron microscopy (SEM). Inductively coupled plasma atomic emission spectrometry (ICP) was used to determine the 24-hour cumulative release of copper ions in Tris solution. The biocompatibility of the powders was measured by CCK8 and live/dead staining. The effect of the powders on bone differentiation was measured by ALP activity. the OCP powder was a long strip chip like crystal structure under SEM. The doping of Cu2+ made the chip structure smaller and finer. The main diffraction peak of OCP can be seen at 2θ=4.7° for all the five powders. XRF showed that the main composition of the powders was still Ca, P and O. The mass fractions of Cu2+ in the powders were 0.1Cu-OCP: 0.02%, 0.5Cu-OCP: 0.08%, Cu-OCP: 0.23%, and 5Cu-OCP: 0.76%, respectively. ICP results showed that Ca, P and Cu were released slowly in 24 hours in Tris solution. CCK8 and live/dead staining showed that all kinds of copper-doped OCP powders had good biocompatibility with mBMSCs, and could promote osteogenic differentiation. Among them, 0.5Cu-OCP promoted the proliferation and ALP activity of mBMSCs significantly. In conclusion, in this study, copper ions were successfully doped into OCP powder, and the physical and chemical properties of OCP powders doped with copper ions were characterized. In vitro cell experiment confirmed that the powders had good biocompatibility, non-toxic to mBMSCs, and could promote the proliferation of mBMSCs in vitro.
Published in | Journal of Biomaterials (Volume 5, Issue 1) |
DOI | 10.11648/j.jb.20210501.12 |
Page(s) | 10-15 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2021. Published by Science Publishing Group |
Octacalcium Phosphate, Copper Ions, Osteogenesis, Bone Regeneration
[1] | Amini AR, Laurencin CT, Nukavarapu SP: Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 2012, 40: 363-408. |
[2] | Campana V, Milano G, Pagano E, Barba M, Cicione C, Salonna G, Lattanzi W, Logroscino G: Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci Mater Med 2014, 25 (10): 2445-61. |
[3] | Brown WE, Smith JP, Lehr JR, Frazier AW: Crystallographic and chemical relations between octacalcium phosphate and hydroxyapatite. Nature 1962, 196: 1050-5. |
[4] | T. Kurobane, Y. Shiwaku, T. Anada, R. Hamai, K. Tsuchiya, K. Baba, M. Iikubo, T. Takahashi, O. Suzuki: Angiogenesis involvement by octacalcium phosphate-gelatin composite-driven bone regeneration in rat calvaria critical-sized defect. Acta Biomaterialia 2019, 88: 514-526. |
[5] | Kamakura S, Sasano Y, Shimizu T, Hatori K, Suzuki O, Kagayama M: Implanted octacalcium phosphate is more resorbable than beta-tricalcium phosphate and hydroxyapatite. Journal of biomedical materials research 2002, 59 (1): 29-34. |
[6] | Habibovic P, van der Valk CM, van Blitterswijk CA, De Groot K, Meijer G: Influence of octacalcium phosphate coating on osteoinductive properties of biomaterials. Journal of materials science Materials in medicine 2004, 15 (4): 373-80. |
[7] | O. Suzuki, S. Kamakura, T. Katagiri, M. Nakamura, B. Zhao, Y. Honda, R. Kamijo: Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite. Biomaterials 2006, 27 (13): 2671-2681. |
[8] | L. Forte, P. Torricelli, E. Boanini, M. Gazzano, M. Fini, A. Bigi: Antiresorptive and anti-angiogenetic octacalcium phosphate functionalized with bisphosphonates. An in vitro tri-culture study. Acta Biomaterialia 2017, 54: 419-428. |
[9] | M. Bost, S. Houdart, M. Oberli, E. Kalonji, J.-F. Huneau, I. Margaritis: Dietary copper and human health. Current evidence and unresolved issues. Trace Elem. Med Biol 2016, 35: 107-115. |
[10] | A. Robert, Y. Liu, M. Nguyen, B. Meunier: Regulation of Copper and Iron Homeostasis by Metal Chelators: A Possible Chemotherapy for Alzheimer's Disease. Acc. Chem Res 2015, 48 (5): 1332-1339. |
[11] | Y. Hatori, Y. Yan, K. Schmidt, E. Furukawa, N. M. Hasan, N. Yang, C.-N. Liu, S. Sockanathan, S. Lutsenko: Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway. Nature Communications 2016, 7: 10640. |
[12] | T. Kosonen, J. Y. Uriu-Hare, M. S. Clegg, C. L. Keen, R. B. Rucker: Incorporation of copper into lysyl oxidase. The Biochemical journal 1997, 327 (1): 283-9. |
[13] | M. Shi, Z. Chen, S. Farnaghi, T. Friis, X. Mao, Y. Xiao, C. Wu: Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis. Acta Biomaterialia 2016, 30: 334-344. |
[14] | S. Meininger, S. Mandal, A. Kumar, J. Groll, B. Basu, U. Gbureck: Strength reliability and in vitro degradation of three-dimensional powder printed strontium-substituted magnesium phosphate scaffolds. Acta Biomaterialia 2016, 31: 401-411. |
[15] | H. Hu, Y. Tang, L. Pang, C. Lin, W. Huang, D. Wang, W. Jia: Angiogenesis and Full Thickness Wound Healing Efficiency of a Copper-Doped Borate Bioactive Glass/Poly (lactic-co-glycolic acid) Dressing Loaded with Vitamin E in Vivo and in Vitro. ACS Applied Materials & Interfaces 2018, 10 (27): 22939-22950. |
[16] | Suzuki O, Shiwaku Y, Hamai R: Octacalcium phosphate bone substitute materials: Comparison between properties of biomaterials and other calcium phosphate materials. Dent Mater J 2020, 39 (2): 187-199. |
[17] | Kouketsu A, Matsui K, Kawai T, Ezoe Y, Yanagisawa T, Yasuda A, Takahashi T, Kamakura S: Octacalcium phosphate collagen composite stimulates the expression and activity of osteogenic factors to promote bone regeneration. J Tissue Eng Regen Med 2020, 14 (1): 99-107. |
[18] | W. Yang, J. Wang, L. Liu, X. Zhu, X. Wang, Z. Liu, Z. Wang, L. Yang, G. Liu, Biol: Effect of High Dietary Copper on Somatostatin and Growth Hormone-Releasing Hormone Levels in the Hypothalami of Growing Pigs. Trace Elem. Res 2011, 143: 893-900. |
[19] | A. Gajewska, B. Gajkowska, B. Pajak, J. Styrna, K. Kochman, Brain Res: Impaired growth hormone-releasing hormone neurons ultrastructure and peptide accumulation in the arcuate nucleus of mosaic mice with altered copper metabolism. Bull 2009, 80 (3): 128-132. |
[20] | J. R. Prohaska, A. A. Gybina, J: Intracellular Copper Transport in Mammals. Nutr 2004, 134 (5): 1003-1006. |
[21] | Wang P, Yuan Y, Xu K, Zhong H, Yang Y, Jin S, Yang K, Qi X: Biological applications of copper-containing materials. Bioact Mater 2020, 6 (4): 916-927. |
[22] | Xu D, Qian J, Guan X, Ren L, Yang K, Huang X, Zhang S, Chai Y, Wu X, Wu H, Zhang X, Yang K, Yu B: Copper-Containing Alloy as Immunoregulatory Material in Bone Regeneration via Mitochondrial Oxidative Stress. Front Bioeng Biotechnol 2021, 8: 620629. |
[23] | L. Ren, H. M. Wong, C. H. Yan, K. W. Yeung, K. Yang, J: Osteogenic ability of Cu-bearing stainless steel. Biomed. Mater. Res 2015, 103 (7): 1433-1444. |
[24] | C. Wu, Y. Zhou, M. Xu, P. Han, L. Chen, J. Chang, Y. Xiao: Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity. Biomaterials 2013, 34 (2): 422-433. |
[25] | Y. Lu, L. Li, Y. Zhu, X. Wang, M. Li, Z. Lin, X. Hu, Y. Zhang, Q. Yin, H. Xia: Multifunctional Copper-Containing Carboxymethyl Chitosan/Alginate Scaffolds for Eradicating Clinical Bacterial Infection and Promoting Bone Formation. ACS Appl. Mater. Interfaces 2018, 10 (1): 127-138. |
[26] | W. Zhang, Q. Chang, L. Xu, G. Li, G. Yang, X. Ding, X. Wang, D. Cui, X. Jiang: Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α. Adv. Healthcare Mater 2016, 5 (11): 1299-1309. |
[27] | Y. Lu, L. Li, Z. Lin, L. Wang, L. Lin, M. Li, Y. Zhang, Q. Li, H. Xia: A New Treatment Modality for Rheumatoid Arthritis: Combined Photothermal and Photodynamic Therapy Using Cu7.2S4 Nanoparticles. Adv. Healthcare Mater 2018, 7 (14): 1800013-1800023. |
[28] | P. M. Gomez, L. Fourcade, M. A. Mateescu: On some new species of AncorabolidaeSars, 1909 from the Gulf of California: the genera Ceratonotus Sars, 1909, and Dendropsyllus Conroy-Dalton, 2003 (Crustacea, Copepoda, Harpacticoida). J. Paquin, Anal. Biochem 2017, 535: 43-46. |
[29] | Serigano, K., Sakai, D., Hiyama, A., Tamura, F., Tanaka, M., & Mochida, J: Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. Journal of Orthopaedic Research 2010, 28 (10): 1267-75. |
APA Style
Jiwen Chen, Changshun Chen, Yunjun Wu, Riwang Li, Youjie Liu, et al. (2021). Synthesis and Characterization of Copper Ions Doped Octacalcium Phosphate Powders with Enhanced Osteogenic Property. Journal of Biomaterials, 5(1), 10-15. https://doi.org/10.11648/j.jb.20210501.12
ACS Style
Jiwen Chen; Changshun Chen; Yunjun Wu; Riwang Li; Youjie Liu, et al. Synthesis and Characterization of Copper Ions Doped Octacalcium Phosphate Powders with Enhanced Osteogenic Property. J. Biomater. 2021, 5(1), 10-15. doi: 10.11648/j.jb.20210501.12
AMA Style
Jiwen Chen, Changshun Chen, Yunjun Wu, Riwang Li, Youjie Liu, et al. Synthesis and Characterization of Copper Ions Doped Octacalcium Phosphate Powders with Enhanced Osteogenic Property. J Biomater. 2021;5(1):10-15. doi: 10.11648/j.jb.20210501.12
@article{10.11648/j.jb.20210501.12, author = {Jiwen Chen and Changshun Chen and Yunjun Wu and Riwang Li and Youjie Liu and Yiwan Shi and Huige Hou and Junting Liu and Huajun Wang and Tingting Wu and Xiaofei Zheng}, title = {Synthesis and Characterization of Copper Ions Doped Octacalcium Phosphate Powders with Enhanced Osteogenic Property}, journal = {Journal of Biomaterials}, volume = {5}, number = {1}, pages = {10-15}, doi = {10.11648/j.jb.20210501.12}, url = {https://doi.org/10.11648/j.jb.20210501.12}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jb.20210501.12}, abstract = {Diverse biomaterials have been designed to promote bone regeneration, and due to their potential side effects of adverse inflammation and immune responses, only a few synthetic biomaterials displayed successful clinical outcomes in repairing bone defects. The repair of bone defects remains a big challenge for orthopedists. This study was dedicated to the synthesis of copper-doped octacalcium phosphate powder Cu-OCP with good bone repair potential, which provides a new way for the construction of bone regeneration biomaterials. Five kinds of copper-doped powders, OCP, 0.1Cu-OCP, 0.5Cu-OCP, Cu-OCP and 5Cu-OCP, were synthesized by chemical homogeneous precipitation method. The phases of the powders were analyzed by X-ray diffraction (XRD). The elemental compositions of the powders were analyzed by X-ray fluorescence spectrometer (XRF). The microstructures of the powders were observed by scanning electron microscopy (SEM). Inductively coupled plasma atomic emission spectrometry (ICP) was used to determine the 24-hour cumulative release of copper ions in Tris solution. The biocompatibility of the powders was measured by CCK8 and live/dead staining. The effect of the powders on bone differentiation was measured by ALP activity. the OCP powder was a long strip chip like crystal structure under SEM. The doping of Cu2+ made the chip structure smaller and finer. The main diffraction peak of OCP can be seen at 2θ=4.7° for all the five powders. XRF showed that the main composition of the powders was still Ca, P and O. The mass fractions of Cu2+ in the powders were 0.1Cu-OCP: 0.02%, 0.5Cu-OCP: 0.08%, Cu-OCP: 0.23%, and 5Cu-OCP: 0.76%, respectively. ICP results showed that Ca, P and Cu were released slowly in 24 hours in Tris solution. CCK8 and live/dead staining showed that all kinds of copper-doped OCP powders had good biocompatibility with mBMSCs, and could promote osteogenic differentiation. Among them, 0.5Cu-OCP promoted the proliferation and ALP activity of mBMSCs significantly. In conclusion, in this study, copper ions were successfully doped into OCP powder, and the physical and chemical properties of OCP powders doped with copper ions were characterized. In vitro cell experiment confirmed that the powders had good biocompatibility, non-toxic to mBMSCs, and could promote the proliferation of mBMSCs in vitro.}, year = {2021} }
TY - JOUR T1 - Synthesis and Characterization of Copper Ions Doped Octacalcium Phosphate Powders with Enhanced Osteogenic Property AU - Jiwen Chen AU - Changshun Chen AU - Yunjun Wu AU - Riwang Li AU - Youjie Liu AU - Yiwan Shi AU - Huige Hou AU - Junting Liu AU - Huajun Wang AU - Tingting Wu AU - Xiaofei Zheng Y1 - 2021/04/16 PY - 2021 N1 - https://doi.org/10.11648/j.jb.20210501.12 DO - 10.11648/j.jb.20210501.12 T2 - Journal of Biomaterials JF - Journal of Biomaterials JO - Journal of Biomaterials SP - 10 EP - 15 PB - Science Publishing Group SN - 2640-2629 UR - https://doi.org/10.11648/j.jb.20210501.12 AB - Diverse biomaterials have been designed to promote bone regeneration, and due to their potential side effects of adverse inflammation and immune responses, only a few synthetic biomaterials displayed successful clinical outcomes in repairing bone defects. The repair of bone defects remains a big challenge for orthopedists. This study was dedicated to the synthesis of copper-doped octacalcium phosphate powder Cu-OCP with good bone repair potential, which provides a new way for the construction of bone regeneration biomaterials. Five kinds of copper-doped powders, OCP, 0.1Cu-OCP, 0.5Cu-OCP, Cu-OCP and 5Cu-OCP, were synthesized by chemical homogeneous precipitation method. The phases of the powders were analyzed by X-ray diffraction (XRD). The elemental compositions of the powders were analyzed by X-ray fluorescence spectrometer (XRF). The microstructures of the powders were observed by scanning electron microscopy (SEM). Inductively coupled plasma atomic emission spectrometry (ICP) was used to determine the 24-hour cumulative release of copper ions in Tris solution. The biocompatibility of the powders was measured by CCK8 and live/dead staining. The effect of the powders on bone differentiation was measured by ALP activity. the OCP powder was a long strip chip like crystal structure under SEM. The doping of Cu2+ made the chip structure smaller and finer. The main diffraction peak of OCP can be seen at 2θ=4.7° for all the five powders. XRF showed that the main composition of the powders was still Ca, P and O. The mass fractions of Cu2+ in the powders were 0.1Cu-OCP: 0.02%, 0.5Cu-OCP: 0.08%, Cu-OCP: 0.23%, and 5Cu-OCP: 0.76%, respectively. ICP results showed that Ca, P and Cu were released slowly in 24 hours in Tris solution. CCK8 and live/dead staining showed that all kinds of copper-doped OCP powders had good biocompatibility with mBMSCs, and could promote osteogenic differentiation. Among them, 0.5Cu-OCP promoted the proliferation and ALP activity of mBMSCs significantly. In conclusion, in this study, copper ions were successfully doped into OCP powder, and the physical and chemical properties of OCP powders doped with copper ions were characterized. In vitro cell experiment confirmed that the powders had good biocompatibility, non-toxic to mBMSCs, and could promote the proliferation of mBMSCs in vitro. VL - 5 IS - 1 ER -