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Metal-Doped Brushite Cement for Bone Regeneration

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Abstract

For the past several years, calcium phosphate cement was used in the biomedical applications. Outstanding biocompatibility, good bioactivity, self-setting qualities, minimum setting degree, appropriate toughness, and simple shape to accommodate any difficult geometry are among their most notable attributes. Calcium phosphate has some types and brushite is one of the most attractive mineral for bone repair application. Brushite is extensively employed in filling fractures and trauma treatments as a bone substituted material. This kind of material can potentially be used as a medicine delivery device. The replacement of metal, such as magnesium, zinc, and strontium ions, into the calcium phosphate structure is a major research topic these days. Brushite cement has low mechanical strength and quick setting rate. It is possible to produce biomaterials with higher mechanical characteristics. By adding metal that are great potential in controlling cellular density when included into biomaterials. As a result, it is a successful method to develop quite well regenerative medicine. This paper provides a detailed summary of the present achievements of metal-doped brushite cement for bone repair and healing process. The major purpose of this work is to give a simple but thorough analysis of current successes in brushite cement doped with Zn, Mg, Sr, and other ions as well as to highlight new advancements and prospects. The impact of metal replacement on cement physical and chemical properties, including microstructure, setting time, injectability, mechanical property, and ion release, is explored. The metal-doped cement has osteogenesis, angiogenesis, and antibacterial properties, as well as their prospective utility as drug carriers, also considered.

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References

  1. Bohner, M., Gbureck, U., & Barralet, J. E. (2005). Technological issues for the development of more efficient calcium phosphate bone cements: A critical assessment. Biomaterials, 26(33), 6423–6429.

    Google Scholar 

  2. Amini, A. R., Laurencin, C. T., & Nukavarapu, S. P. (2012). Bone tissue engineering: recent advances and challenges. Critical Reviews™ in Biomedical Engineering, 40(5).

  3. Wang, W., & Yeung, K. W. (2017). Bone grafts and biomaterials substitutes for bone defect repair: A review. Bioactive Materials, 2(4), 224–247.

    Google Scholar 

  4. Yilmaz, B., Alshemary, A. Z., & Evis, Z. (2019). Co-doped hydroxyapatites as potential materials for biomedical applications. Microchemical Journal, 144, 443–453.

    Google Scholar 

  5. Bose, S., Al-Kindy, F., Al-Balushi, A., & Rajab, M. M. (2013). Accounting the unaccounted: Case of women’s participation in shellfish harvesting in the Sultanate of Oman. Gender, Technology and Development, 17(1), 31–53.

    Google Scholar 

  6. Surmeneva, M., Lapanje, A., Chudinova, E., Ivanova, A., Koptyug, A., Loza, K., Prymak, O., Epple, M., Ennen-Roth, F., Ulbricht, M., Rijavec, T., & Surmenev, R. (2019). Decreased bacterial colonization of additively manufactured Ti6Al4V metallic scaffolds with immobilized silver and calcium phosphate nanoparticles. Applied Surface Science, 480, 822–829.

    Google Scholar 

  7. Li, L. Y., Cui, L. Y., Liu, B., Zeng, R. C., Chen, X. B., Li, S. Q., Wang, Z. L., & Han, E. H. (2019). Corrosion resistance of glucose-induced hydrothermal calcium phosphate coating on pure magnesium. Applied Surface Science, 465, 1066–1077.

    Google Scholar 

  8. Zhang, J., Dai, C. S., Wei, J., & Wen, Z. H. (2012). Study on the bonding strength between calcium phosphate/chitosan composite coatings and a Mg alloy substrate. Applied Surface Science, 261, 276–286.

    Google Scholar 

  9. Huang, Y., Yan, Y., Pang, X., Ding, Q., & Han, S. (2013). Bioactivity and corrosion properties of gelatin-containing and strontium-doped calcium phosphate composite coating. Applied surface science, 282, 583–589.

    Google Scholar 

  10. Sheikh, Z., Zhang, Y. L., Grover, L., Merle, G. E., Tamimi, F., & Barralet, J. (2015). In vitro degradation and in vivo resorption of dicalcium phosphate cement based grafts. Acta Biomaterialia, 26, 338–346.

    Google Scholar 

  11. Dorozhkin, S. V. (2011). Self-setting calcium orthophosphate formulations: Cements, concretes, pastes and putties. International Journal of Materials and Chemistry, 1(1), 1–48.

    Google Scholar 

  12. Moses, J. C., Dey, M., Devi, K. B., Roy, M., Nandi, S. K., & Mandal, B. B. (2019). Synergistic effects of silicon/zinc doped brushite and silk scaffolding in augmenting the osteogenic and angiogenic potential of composite biomimetic bone grafts. ACS Biomaterials Science & Engineering, 5(3), 1462–1475.

    Google Scholar 

  13. Mirtchi, A. A., Lemaitre, J., & Terao, N. (1989). Calcium phosphate cements: Study of the β-tricalcium phosphate—monocalcium phosphate system. Biomaterials, 10(7), 475–480.

    Google Scholar 

  14. Wang, S., Xu, C., Yu, S., Wu, X., Jie, Z., & Dai, H. (2019). Citric acid enhances the physical properties, cytocompatibility and osteogenesis of magnesium calcium phosphate cement. Journal of the Mechanical Behavior of Biomedical Materials, 94, 42–50.

    Google Scholar 

  15. Bohner, M., & Gbureck, U. (2008). Thermal reactions of brushite cements. Journal of Biomedical Materials Research Part B: Applied Biomaterials: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, 84(2), 375–385.

    Google Scholar 

  16. Frayssinet, P., Gineste, L., Conte, P., Fages, J., & Rouquet, N. (1998). Short-term implantation effects of a DCPD-based calcium phosphate cement. Biomaterials, 19(11–12), 971–977.

    Google Scholar 

  17. Sudhan, N., Anitta, S., Meenakshi, S., & Sekar, C. (2022). Brushite nanoparticles based electrochemical sensor for detection of uric acid, xanthine, hypoxanthine and caffeine. Analytical Biochemistry, 659, 114947.

    Google Scholar 

  18. Rödel, M., Teßmar, J., Groll, J., & Gbureck, U. (2022). Dual setting brushite—gelatin cement with increased ductility and sustained drug release. Journal of Biomaterials Applications, 36(10), 1882–1898.

    Google Scholar 

  19. Nandi, S. K., Roy, M., Bandyopadhyay, A., & Bose, S. (2023). In vivo biocompatibility of SrO and MgO doped brushite cements. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 111(3), 599–609.

    Google Scholar 

  20. Schatkoski, V. M., do Amaral Montanheiro, T. L., de Menezes, B. R. C., Pereira, R. M., Rodrigues, K. F., Ribas, R. G., da Silva, D. M., & Thim, G. P. (2021). Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering. Ceramics International, 47(3), 2999-3012

  21. Bose, S., Fielding, G., Tarafder, S., & Bandyopadhyay, A. (2013). Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics. Trends in Biotechnology, 31(10), 594–605.

    Google Scholar 

  22. Rude, R. K. (1998). Magnesium deficiency: A cause of heterogenous disease in humans. Journal of Bone and Mineral Research, 13(4), 749–758.

    Google Scholar 

  23. Al-Ghamdi, S. M., Cameron, E. C., & Sutton, R. A. (1994). Magnesium deficiency: Pathophysiologic and clinical overview. American Journal of Kidney Diseases, 24(5), 737–752.

    Google Scholar 

  24. Reginster, J. Y., Seeman, E., De Vernejoul, M. C., Adami, S., Compston, J., Phenekos, C., Devogelaer, J. P., Curiel, M. D., Sawicki, A., Goemaere, S., Sorensen, O. H., Felsenberg, D., & Meunier, P. J. (2005). Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. The Journal of Clinical Endocrinology & Metabolism, 90(5), 2816–2822.

    Google Scholar 

  25. Graber, M. L. (1995). Magnesium deficiency: Pathophysiologic and clinical overview. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 25(6), 973–973.

    Google Scholar 

  26. Saghiri, M. A., Asatourian, A., Orangi, J., Sorenson, C. M., & Sheibani, N. (2015). Functional role of inorganic trace elements in angiogenesis—Part II: Cr, Si, Zn, Cu, and S. Critical Reviews in Oncology/Hematology, 96(1), 143–155.

    Google Scholar 

  27. Schamel, M., Bernhardt, A., Quade, M., Würkner, C., Gbureck, U., Moseke, C., Gelinsky, M., & Lode, A. (2017). Cu2+, Co2+ and Cr3+ doping of a calcium phosphate cement influences materials properties and response of human mesenchymal stromal cells. Materials Science and Engineering: C, 73, 99–110.

    Google Scholar 

  28. Mokabber, T., Cao, H. T., Norouzi, N., Van Rijn, P., & Pei, Y. T. (2020). Antimicrobial electrodeposited silver-containing calcium phosphate coatings. ACS Applied Materials & Interfaces, 12(5), 5531–5541.

    Google Scholar 

  29. Uskoković, V., Graziani, V., Wu, V. M., Fadeeva, I. V., Fomin, A. S., Presniakov, I. A., Fosca, M., Ortenzi, M., Caminiti, R., & Rau, J. V. (2019). Gold is for the mistress, silver for the maid: Enhanced mechanical properties, osteoinduction and antibacterial activity due to iron doping of tricalcium phosphate bone cements. Materials Science and Engineering: C, 94, 798–810.

    Google Scholar 

  30. Alkhraisat, M. H., Cabrejos-Azama, J., Rodríguez, C. R., Jerez, L. B., & Cabarcos, E. L. (2013). Magnesium substitution in brushite cements. Materials Science and Engineering: C, 33(1), 475–481.

    Google Scholar 

  31. Saleh, A. T., Ling, L. S., & Hussain, R. (2016). Injectable magnesium-doped brushite cement for controlled drug release application. Journal of Materials Science, 51, 7427–7439.

    Google Scholar 

  32. Hurle, K., Oliveira, J. M., Reis, R. L., Pina, S., & Goetz-Neunhoeffer, F. (2021). Ion-doped brushite cements for bone regeneration. Acta Biomaterialia, 123, 51–71.

    Google Scholar 

  33. Adawy, A., & Diaz, R. (2022). Probing the Structure, Cytocompatibility, and Antimicrobial Efficacy of Silver-, Strontium-, and Zinc-Doped Monetite. ACS Applied Bio Materials, 5(4), 1648–1657.

    Google Scholar 

  34. Uysal, I., Yilmaz, B., & Evis, Z. (2021). Zn-doped hydroxyapatite in biomedical applications. Journal of the Australian Ceramic Society, 57(3), 869–897.

    Google Scholar 

  35. Hadley, K. B., Newman, S. M., & Hunt, J. R. (2010). Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats. The Journal of Nutritional Biochemistry, 21(4), 297–303.

    Google Scholar 

  36. Bohner, M., & Baroud, G. (2005). Injectability of calcium phosphate pastes. Biomaterials, 26(13), 1553–1563.

    Google Scholar 

  37. Singh, S. S., Roy, A., Lee, B. E., Ohodnicki, J., Loghmanian, A., Banerjee, I., & Kumta, P. N. (2014). A study of strontium doped calcium phosphate coatings on AZ31. Materials Science and Engineering: C, 40, 357–365.

    Google Scholar 

  38. Lakrat, M., Jodati, H., Mejdoubi, E. M., & Evis, Z. (2023). Synthesis and characterization of pure and Mg, Cu, Ag, and Sr doped calcium-deficient hydroxyapatite from brushite as precursor using the dissolution-precipitation method. Powder Technology, 413, 118026.

    Google Scholar 

  39. Turkoz, M., Atilla, A. O., & Evis, Z. (2013). Silver and fluoride doped hydroxyapatites: Investigation by microstructure, mechanical and antibacterial properties. Ceramics International, 39(8), 8925–8931.

    Google Scholar 

  40. Cummings, H., Han, W., Vahabzadeh, S., & Elsawa, S. F. (2017). Cobalt-doped brushite cement: Preparation, characterization, and in vitro interaction with osteosarcoma cells. JOM Journal of the Minerals Metals and Materials Society, 69, 1348–1353.

    Google Scholar 

  41. Vahabzadeh, S., Fleck, S., Duvvuru, M. K., & Cummings, H. (2019). Effects of cobalt on physical and mechanical properties and in vitro degradation behavior of brushite cement. JOM Journal of the Minerals Metals and Materials Society, 71, 315–320.

    Google Scholar 

  42. Rau, J. V., Wu, V. M., Graziani, V., Fadeeva, I. V., Fomin, A. S., Fosca, M., & Uskoković, V. (2017). The Bone Building Blues: Self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria. Materials Science and Engineering: C, 79, 270–279.

    Google Scholar 

  43. Spaeth, K., Goetz-Neunhoeffer, F., & Hurle, K. (2023). The effect of Cu2+ doping in β-tricalcium phosphate on the hydration mechanism of a brushite cement. Materials Today Chemistry, 27, 101288.

    Google Scholar 

  44. Ewald, A., Hösel, D., Patel, S., Grover, L. M., Barralet, J. E., & Gbureck, U. (2011). Silver-doped calcium phosphate cements with antimicrobial activity. Acta Biomaterialia, 7(11), 4064–4070.

    Google Scholar 

  45. Rentsch, B., Bernhardt, A., Henß, A., Ray, S., Rentsch, C., Schamel, M., Gbureck, U., Gelinsky, M., Rammelt, S., & Lode, A. (2018). Trivalent chromium incorporated in a crystalline calcium phosphate matrix accelerates materials degradation and bone formation in vivo. Acta Biomaterialia, 69, 332–341.

    Google Scholar 

  46. Motameni, A., Alshemary, A. Z., Dalgic, A. D., Keskin, D., & Evis, Z. (2021). Lanthanum doped dicalcium phosphate bone cements for potential use as filler for bone defects. Materials Today Communications, 26, 101774.

    Google Scholar 

  47. Youness, R. A., Taha, M. A., Ibrahim, M., & El-Kheshen, A. (2018). FTIR spectral characterization, mechanical properties and antimicrobial properties of La-doped phosphate-based bioactive glasses. SILICON, 10, 1151–1159.

    Google Scholar 

  48. Li, G., Zhang, N., Zhao, S., Zhang, K., Li, X., Jing, A., Liu, X., & Zhang, T. (2018). Fe-doped brushite bone cements with antibacterial property. Materials Letters, 215, 27–30.

    Google Scholar 

  49. Pan, X., Huang, J., Zhang, K., Pei, Z., Ding, Z., Liang, Y., Gu, Z., Li, G., & Xie, H. (2021). Iron-doped brushite bone cement scaffold with enhanced osteoconductivity and antimicrobial properties for jaw regeneration. Ceramics International, 47(18), 25810–25820.

    Google Scholar 

  50. No, Y. J., Holzmeister, I., Lu, Z., Prajapati, S., Shi, J., Gbureck, U., & Zreiqat, H. (2019). Effect of baghdadite substitution on the physicochemical properties of brushite cements. Materials, 12(10), 1719.

    Google Scholar 

  51. Matsumoto, N., Yoshida, K., Hashimoto, K., & Toda, Y. (2010). Dissolution mechanisms of β-tricalcium phosphate doped with monovalent metal ions. Journal of the Ceramic Society of Japan, 118(1378), 451–457.

    Google Scholar 

  52. Bohner, M., Santoni, B. L. G., & Döbelin, N. (2020). β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta Biomaterialia, 113, 23–41.

    Google Scholar 

  53. Vieira, S. I., Cerqueira, A. R., Pina, S., da Cruz Silva, O. A. B., Abrantes, J. C. C., & Ferreira, J. M. F. (2014). Effects of Mn-doping on the structure and biological properties of β-tricalcium phosphate. Journal of Inorganic Biochemistry, 136, 57–66.

    Google Scholar 

  54. Alshemary, A. Z., Goh, Y. F., Shakir, I., & Hussain, R. (2015). Synthesis, characterization and optical properties of chromium doped β-Tricalcium phosphate. Ceramics International, 41(1), 1663–1669.

    Google Scholar 

  55. Hudon, P., & Jung, I. H. (2015). Critical evaluation and thermodynamic optimization of the CaO-P 2 O 5 system. Metallurgical and Materials Transactions B, 46, 494–522.

    Google Scholar 

  56. Welch, J. H., & Gutt, W. (1961). High-temperature studies of the system calcium oxide–phosphorus pentoxide. Journal of the Chemical Society (Resumed), 874, 4442–4444.

    Google Scholar 

  57. Carrodeguas, R. G., & De Aza, S. (2011). α-Tricalcium phosphate: Synthesis, properties and biomedical applications. Acta Biomaterialia, 7(10), 3536–3546.

    Google Scholar 

  58. Hanak, J. J. (1970). The “multiple-sample concept” in materials research: Synthesis, compositional analysis and testing of entire multicomponent systems. Journal of Materials Science, 5, 964–971.

    Google Scholar 

  59. Dickens, B., Schroeder, L. W., & Brown, W. E. (1974). Crystallographic studies of the role of Mg as a stabilizing impurity in β-Ca3 (PO4) 2. The crystal structure of pure β-Ca3 (PO4) 2. Journal of Solid State Chemistry, 10(3), 232–248.

  60. Enderle, R., Götz-Neunhoeffer, F., Göbbels, M., Müller, F. A., & Greil, P. (2005). Influence of magnesium doping on the phase transformation temperature of β-TCP ceramics examined by Rietveld refinement. Biomaterials, 26(17), 3379–3384.

    Google Scholar 

  61. Sarver, J. F., Hoffman, M. V., & Hummel, F. A. (1961). Phase equilibria and tin-activated luminescence in strontium orthophosphate systems. Journal of the Electrochemical Society, 108(12), 1103.

    Google Scholar 

  62. Gu, Y., Zhang, J., Zhang, X., Liang, G., Xu, T., & Niu, W. (2019). Three-dimensional printed Mg-doped β-TCP bone tissue engineering scaffolds: Effects of magnesium ion concentration on osteogenesis and angiogenesis in vitro. Tissue Engineering and Regenerative Medicine, 16, 415–429.

    Google Scholar 

  63. Fielding, G. A., Sarkar, N., Vahabzadeh, S., & Bose, S. (2019). Regulation of osteogenic markers at late stage of osteoblast differentiation in silicon and zinc doped porous TCP. Journal of Functional Biomaterials, 10(4), 48.

    Google Scholar 

  64. Tas, A. C., Bhaduri, S. B., & Jalota, S. (2007). Preparation of Zn-doped β-tricalcium phosphate (β-Ca3 (PO4) 2) bioceramics. Materials Science and Engineering: C, 27(3), 394–401.

    Google Scholar 

  65. Curran, D. J., Fleming, T. J., Towler, M. R., & Hampshire, S. (2011). Mechanical parameters of strontium doped hydroxyapatite sintered using microwave and conventional methods. Journal of the Mechanical Behavior of Biomedical Materials, 4(8), 2063–2073.

    Google Scholar 

  66. Roy, M., & Bose, S. (2012). Osteoclastogenesis and osteoclastic resorption of tricalcium phosphate: Effect of strontium and magnesium doping. Journal of Biomedical Materials Research Part A, 100(9), 2450–2461.

    Google Scholar 

  67. Gomes, S., Vichery, C., Descamps, S., Martinez, H., Kaur, A., Jacobs, A., Nedelec, J. M., Renaudin, G., & Renaudin, G. (2018). Cu-doping of calcium phosphate bioceramics: From mechanism to the control of cytotoxicity. Acta Biomaterialia, 65, 462–474.

    Google Scholar 

  68. Veljovic, D., Matic, T., Stamenic, T., Kojic, V., Dimitrijevic-Brankovic, S., Lukic, M. J., Jevtic, S., Radovanovic, Z., Petrovic, R., & Janackovic, D. (2019). Mg/Cu co-substituted hydroxyapatite–Biocompatibility, mechanical properties and antimicrobial activity. Ceramics International, 45(17), 22029–22039.

    Google Scholar 

  69. Matsumoto, N., Sato, K., Yoshida, K., Hashimoto, K., & Toda, Y. (2009). Preparation and characterization of β-tricalcium phosphate co-doped with monovalent and divalent antibacterial metal ions. Acta Biomaterialia, 5(8), 3157–3164.

    Google Scholar 

  70. Adzila, S., Murad, M., & Sopyan, I. (2012). Doping metal into calcium phosphate phase for better performance of bone implant materials. Recent Patents on Materials Science, 5(1), 18–47.

    Google Scholar 

  71. Marques, C. F., Lemos, A., Vieira, S. I., e Silva, O. D. C., Bettencourt, A., & Ferreira, J. M. F. (2016). Antibiotic-loaded Sr-doped porous calcium phosphate granules as multifunctional bone grafts. Ceramics International, 42(2), 2706-2716

  72. Hsu, F. Y., Tsai, S. W., Lan, C. W., & Wang, Y. J. (2005). An in vivo study of a bone grafting material consisting of hydroxyapatite and reconstituted collagen. Journal of Materials Science: Materials in Medicine, 16, 341–345.

    Google Scholar 

  73. Tian, Z., Guo, Y., Yang, X., Guo, K., Ji, J., & Hao, S. (2022). Nano calcium-deficient hydroxyapatite/O-carboxymethyl Chitosan-CaCl2 Microspheres Loaded with rhein for bone defect repair. Journal of Bionic Engineering, 19(4), 1087–1099.

    Google Scholar 

  74. Weitao, Y., Kangmei, K., Xinjia, W., & Weili, Q. (2008). Bone regeneration using an injectable calcium phosphate/autologous iliac crest bone composites for segmental ulnar defects in rabbits. Journal of Materials Science: Materials in Medicine, 19(6), 2485–2492.

    Google Scholar 

  75. Marote, A., Cerqueira, A. R., Calado, A. J., Abrantes, J. C. C., Olhero, S., e Silva, O. D. C., Vieira, S.I., & Ferreira, J. M. F. (2017). Injectable MnSr-doped brushite bone cements with improved biological performance. Journal of Materials Chemistry B, 5(15), 2775-2787

  76. Pina, S., Torres, P. M., Goetz-Neunhoeffer, F., Neubauer, J., & Ferreira, J. M. F. (2010). Newly developed Sr-substituted α-TCP bone cements. Acta Biomaterialia, 6(3), 928–935.

    Google Scholar 

  77. Pina, S., Torres, P. M. C., & Ferreira, J. M. F. (2010). Injectability of brushite-forming Mg-substituted and Sr-substituted α-TCP bone cements. Journal of Materials Science: Materials in Medicine, 21, 431–438.

    Google Scholar 

  78. Graziani, V., Fosca, M., Egorov, A. A., Zobkov, Y. V., Fedotov, A. Y., Baranchikov, A. E., Ortenzi, M., Caminiti, R., Komlev, V. S., & Rau, J. V. (2016). Zinc-releasing calcium phosphate cements for bone substitute materials. Ceramics International, 42(15), 17310–17316.

    Google Scholar 

  79. Li, S., Xie, Q., & Mo, A. (2022). A biphasic material combined with injectable platelet-rich fibrin for the potential regeneration of oral soft and hard tissues. Journal of Materials Science, 57(16), 7923–7940.

    Google Scholar 

  80. Zhang, L., Zhang, C., Zhang, R., Jiang, D., Zhu, Q., & Wang, S. (2019). Extraction and characterization of HA/β-TCP biphasic calcium phosphate from marine fish. Materials Letters, 236, 680–682.

    Google Scholar 

  81. Zaffe, D., Leghissa, G. C., Pradelli, J., & Botticelli, A. R. (2005). Histological study on sinus lift grafting by Fisiograft and Bio-Oss. Journal of Materials Science: Materials in Medicine, 16(9), 789–793.

    Google Scholar 

  82. Amirian, J., Makkar, P., Lee, G. H., Paul, K., & Lee, B. T. (2020). Incorporation of alginate-hyaluronic acid microbeads in injectable calcium phosphate cement for improved bone regeneration. Materials Letters, 272, 127830.

    Google Scholar 

  83. Jurgelane, I., Buss, A., Putnina, M., Loca, D., & Locs, J. (2021). Effect of sintering temperature on sorption properties and compressive strength of calcium phosphate ceramic granules. Materials Letters, 282, 128858.

    Google Scholar 

  84. Correa, T. H. A., Toledo, R., Silva, N. S., & Holanda, J. N. F. (2019). Novel nano-sized biphasic calcium phosphate bioceramics (β-CPP/β-TCP) derived of lime mud waste. Materials Letters, 243, 17–20.

    Google Scholar 

  85. Taha, A., Akram, M., Jawad, Z., Alshemary, A. Z., & Hussain, R. (2017). Strontium doped injectable bone cement for potential drug delivery applications. Materials Science and Engineering: C, 80, 93–101.

    Google Scholar 

  86. Downes, S., Archer, R. S., Kayser, M. V., Patel, M. P., & Braden, M. (1994). The regeneration of articular cartilage using a new polymer system. Journal of Materials Science: Materials in Medicine, 5, 88–95.

    Google Scholar 

  87. Rau, J. V., Fosca, M., Graziani, V., Egorov, A. A., Zobkov, Y. V., Fedotov, A. Y., Ortenzi, M., Caminiti, R., Baranchikov, A. E., & Komlev, V. S. (2016). Silver-doped calcium phosphate bone cements with antibacterial properties. Journal of Functional Biomaterials, 7(2), 10.

    Google Scholar 

  88. Vahabzadeh, S., Bandyopadhyay, A., Bose, S., Mandal, R., & Nandi, S. K. (2015). IGF-loaded silicon and zinc doped brushite cement: Physico-mechanical characterization and in vivo osteogenesis evaluation. Integrative Biology, 7(12), 1561–1573.

    Google Scholar 

  89. Li, X., Li, G., Zhang, K., Pei, Z., Zhao, S., & Li, J. (2021). Cu-loaded Brushite bone cements with good antibacterial activity and operability. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 109(6), 877–889.

    Google Scholar 

  90. Carmeliet, P. (2003). Angiogenesis in health and disease. Nature Medicine, 9(6), 653–660.

    Google Scholar 

  91. Nie, L., Li, X., Chang, P., Liu, S., Wei, Q., Guo, Q., Wu, Q., Fan, L., Okoro, O. V., & Shavandi, A. (2022). A fast method for in vitro biomineralization of PVA/alginate/biphasic calcium phosphate hydrogel. Materials Letters, 308, 131182.

    Google Scholar 

  92. Xu, H. H., Wang, P., Wang, L., Bao, C., Chen, Q., Weir, M. D., Chow, L. C., Zhao, L., Zhou, X., & Reynolds, M. A. (2017). Calcium phosphate cements for bone engineering and their biological properties. Bone Research, 5(1), 1–19.

    Google Scholar 

  93. Laskus, A., & Kolmas, J. (2017). Ionic substitutions in non-apatitic calcium phosphates. International Journal of Molecular Sciences, 18(12), 2542.

    Google Scholar 

  94. Dziadek, M., Zima, A., Cichoń, E., Czechowska, J., & Ślósarczyk, A. (2020). Biomicroconcretes based on the hybrid HAp/CTS granules, α-TCP and pectins as a novel injectable bone substitutes. Materials Letters, 265, 127457.

    Google Scholar 

  95. Jayasree, R., Kumar, T. S., Venkateswari, R., Nankar, R. P., & Doble, M. (2019). Eggshell derived brushite bone cement with minimal inflammatory response and higher osteoconductive potential. Journal of Materials Science: Materials in Medicine, 30, 1–14.

    Google Scholar 

  96. Raja, N., Han, S. H., Cho, M., Choi, Y. J., Jin, Y. Z., Park, H., Lee, J. H., & Yun, H. S. (2022). Effect of porosity and phase composition in 3D printed calcium phosphate scaffolds on bone tissue regeneration in vivo. Materials & Design, 219, 110819.

    Google Scholar 

  97. Theuretzbacher, U. (2012). Accelerating resistance, inadequate antibacterial drug pipelines and international responses. International Journal of Antimicrobial Agents, 39(4), 295–299.

    Google Scholar 

  98. Lee, G. H., Makkar, P., Paul, K., & Lee, B. (2017). Incorporation of BMP-2 loaded collagen conjugated BCP granules in calcium phosphate cement based injectable bone substitutes for improved bone regeneration. Materials Science and Engineering: C, 77, 713–724.

    Google Scholar 

  99. Ding, S., Zhang, J., Tian, Y., Huang, B., Yuan, Y., & Liu, C. (2016). Magnesium modification up-regulates the bioactivity of bone morphogenetic protein-2 upon calcium phosphate cement via enhanced BMP receptor recognition and Smad signaling pathway. Colloids and Surfaces B: Biointerfaces, 145, 140–151.

    Google Scholar 

  100. Sterling, J. P. (2014). Silver-resistance, allergy, and blue skin: Truth or urban legend? Burns, 40, S19–S23.

    Google Scholar 

  101. Huang, B., Tian, Y., Zhang, W., Ma, Y., Yuan, Y., & Liu, C. (2017). Strontium doping promotes bioactivity of rhBMP-2 upon calcium phosphate cement via elevated recognition and expression of BMPR-IA. Colloids and Surfaces B: Biointerfaces, 159, 684–695.

    Google Scholar 

  102. Hofmann, M. P., Mohammed, A. R., Perrie, Y., Gbureck, U. J. E. B., & Barralet, J. E. (2009). High-strength resorbable brushite bone cement with controlled drug-releasing capabilities. Acta Biomaterialia, 5(1), 43–49.

    Google Scholar 

  103. Sheikh, Z., Abdallah, M. N., Hanafi, A. A., Misbahuddin, S., Rashid, H., & Glogauer, M. (2015). Mechanisms of in vivo degradation and resorption of calcium phosphate based biomaterials. Materials, 8(11), 7913–7925.

    Google Scholar 

  104. Sayahi, M., Santos, J., El-Feki, H., Charvillat, C., Bosc, F., Karacan, I., Milthrope, B., & Drouet, C. (2020). Brushite (Ca, M) HPO4, 2H2O doping with bioactive ions (M= Mg2+, Sr2+, Zn2+, Cu2+, and Ag+): A new path to functional biomaterials? Materials Today Chemistry, 16, 100230.

    Google Scholar 

  105. Vahabzadeh, S., Fleck, S., Marble, J., Tabatabaei, F., & Tayebi, L. (2020). Role of iron on physical and mechanical properties of brushite cements, and interaction with human dental pulp stem cells. Ceramics international, 46(8), 11905–11912.

    Google Scholar 

  106. Kumar, A., & Mariappan, C. R. (2021). A new biocompatible phosphate free mesoporous calcium borosilicate glass-ceramics for medical application. Materials Letters, 305, 130752.

    Google Scholar 

  107. Peter, B., Pioletti, D. P., Laib, S., Bujoli, B., Pilet, P., Janvier, P., Guicheux, J., Zambelli, P. Y., Bouler, J. M., & Gauthier, O. (2005). Calcium phosphate drug delivery system: Influence of local zoledronate release on bone implant osteointegration. Bone, 36(1), 52–60.

    Google Scholar 

  108. Ginebra, M. P., Traykova, T., & Planell, J. A. (2006). Calcium phosphate cements as bone drug delivery systems: A review. Journal of Controlled Release, 113(2), 102–110.

    Google Scholar 

  109. Laskus, A., Zgadzaj, A., & Kolmas, J. (2018). Selenium-enriched brushite: A novel biomaterial for potential use in bone tissue engineering. International Journal of Molecular Sciences, 19(12), 4042.

    Google Scholar 

  110. Kruppke, B., Wagner, A. S., Rohnke, M., Heinemann, C., Kreschel, C., Gebert, A., Wiesmann, H. P., Mazurek, S., Wenisch, S., & Hanke, T. (2019). Biomaterial based treatment of osteoclastic/osteoblastic cell imbalance–Gelatin-modified calcium/strontium phosphates. Materials Science and Engineering: C, 104, 109933.

    Google Scholar 

  111. Lucas-Aparicio, J., Manchón, Á., Rueda, C., Pintado, C., Torres, J., Alkhraisat, M. H., & López-Cabarcos, E. (2020). Silicon-calcium phosphate ceramics and silicon-calcium phosphate cements: Substrates to customize the release of antibiotics according to the idiosyncrasies of the patient. Materials Science and Engineering: C, 106, 110173.

    Google Scholar 

  112. Gbureck, U., Barralet, J. E., Spatz, K., Grover, L. M., & Thull, R. (2004). Ionic modification of calcium phosphate cement viscosity. Part I: hypodermic injection and strength improvement of apatite cement. Biomaterials, 25(11), 2187–2195..

  113. Hurle, K., Weichhold, J., Brueckner, M., Gbureck, U., Brueckner, T., & Goetz-Neunhoeffer, F. (2018). Hydration mechanism of a calcium phosphate cement modified with phytic acid. Acta Biomaterialia, 80, 378–389.

    Google Scholar 

  114. Medvecky, L., Stulajterova, R., Giretova, M., Sopcak, T., Molcanova, Z., & Koval, K. (2020). Enzymatically hardened calcium phosphate biocement with phytic acid addition. Journal of Materials Science: Materials in Medicine, 31, 1–14.

    Google Scholar 

  115. Pina, S., Olhero, S. M., Gheduzzi, S., Miles, A. W., & Ferreira, J. M. F. (2009). Influence of setting liquid composition and liquid-to-powder ratio on properties of a Mg-substituted calcium phosphate cement. Acta Biomaterialia, 5(4), 1233–1240.

    Google Scholar 

  116. Cabrejos-Azama, J., Alkhraisat, M. H., Rueda, C., Torres, J., Pintado, C., Blanco, L., & López-Cabarcos, E. (2016). Magnesium substitution in brushite cements: Efficacy of a new biomaterial loaded with vancomycin for the treatment of Staphylococcus aureus infections. Materials Science and Engineering: C, 61, 72–78.

    Google Scholar 

  117. Luo, K., Wang, L., Chen, X., Zeng, X., Zhou, S., Zhang, P., & Li, J. (2022). Biocompatible poly (ε-caprolactone)-based shape-memory polyurethane composite scaffold with bone-induced activity. Journal of Bionic Engineering, 1–12.

  118. Alkhraisat, M. H., Rueda, C., & Cabarcos, E. L. (2011). Strontium ions substitution in brushite crystals: The role of strontium chloride. Journal of Functional Biomaterials, 2(2), 31–38.

    Google Scholar 

  119. Fadeeva, I. V., Deyneko, D. V., Knotko, A. V., Olkhov, A. A., Slukin, P. V., Davydova, G. A., Trubitsyna, T. A., Preobrazhenskiy, I. I., Gosteva, A. N., Antoniac, I. V., & Rau, J. V. (2023). Antibacterial composite material based on polyhydroxybutyrate and Zn-doped brushite cement. Polymers, 15(9), 2106.

    Google Scholar 

  120. Laskus-Zakrzewska, A., Zgadzaj, A., & Kolmas, J. (2021). Synthesis and physicochemical characterization of Zn-doped brushite. Ceramics International, 47(6), 7798–7804.

    Google Scholar 

  121. Sopcak, T., Medvecky, L., Giretova, M., Stulajterova, R., Durisin, J., Girman, V., & Faberova, M. (2016). Effect of phase composition of calcium silicate phosphate component on properties of brushite based composite cements. Materials Characterization, 117, 17–29.

    Google Scholar 

  122. Liu, H., Cui, X., Lu, X., Liu, X., Zhang, L., & Chan, T. S. (2021). Mechanism of Mn incorporation into hydroxyapatite: Insights from SR-XRD, Raman, XAS, and DFT calculation. Chemical Geology, 579, 120354.

    Google Scholar 

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Acknowledgements

The authors are grateful to the University of Engineering and Technology, Lahore, Pakistan (ORIC/99 ASRB-614) for funding this research.

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  1. Department of Chemistry, University of Engineering and Technology, GT Road, Lahore, 54890, Pakistan

    Muhammad Aqib, Aneela Anwar, Humayun Ajaz, Ahsan Manzoor, Maham Abid & Zohaib Waheed

  2. Department of Chemistry, University of Engineering and Technology, GT Road, Lahore, 54890, Pakistan

    Samina Akbar

  3. Department of Chemistry, University of Lahore, Lahore, 5400, Pakistan

    Qudsia Kanwal

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  1. Muhammad Aqib
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Aqib, M., Anwar, A., Ajaz, H. et al. Metal-Doped Brushite Cement for Bone Regeneration. J Bionic Eng 20, 2716–2731 (2023). https://doi.org/10.1007/s42235-023-00409-y

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