Advances in magnesium-containing bioceramics for bone repair
Reconstruction of bone defects or fractures caused by ageing, trauma and tumour resection is still a great challenge in clinical treatment. Although autologous bone graft is considered as gold standard, the source of natural bone is limited. In recent years, regenerative therapy based on bioactive materials has been proposed for bone reconstruction. Specially, numerous studies have indicated that bioactive ceramics including silicate and phosphate bioceramics exhibit excellent osteoinductivity and osteoconductivity, further promote bone regeneration. In addition, magnesium (Mg) element, as an indispensable mineral element, plays a vital role in promoting bone mineralisation and formation. In this review, different types of Mg-containing bioceramics including Mg-containing calcium phosphate-based bioceramics (such as Mg-hydroxyapatite, Mg-biphasic calcium phosphate). Mg-containing calcium silicate-based bioceramics (such as Mg2SiO4, Ca2MgSi2O7 and Mg-doped bioglass), Mg-based biocements, Mg-containing metal/polymer-bioceramic composites were systematacially summarised. Additionally, the fabrication technologies and their materiobiological effects were deeply discussed, Clinical applications and perspectives of magnesium-containing bioceramics for bone repair are highlighted. Overall, Mg-containing bioceramics are regarded as regenerative therapy with their optimised performance. Furthermore, more in-depth two-way researches on their performance and structure are essential to satisfy their clinical needs.
Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.
1. Rao, S. H.; Harini, B.; Shadamarshan, R. P. K.; Balagangadharan, K.; Selvamurugan, N. Natural and synthetic polymers/bioceramics/bioactive compounds-mediated cell signalling in bone tissue engineering. Int J Biol Macromol. 2018, 110, 88-96.
2. Tan, B.; Tang, Q.; Zhong, Y.; Wei, Y.; He, L.; Wu, Y.; Wu, J.; Liao, J. Biomaterial-based strategies for maxillofacial tumour therapy and bone defect regeneration. Int J Oral Sci. 2021, 13, 9.
3. Wang, Z.; Wang, Y.; Yan, J.; Zhang, K.; Lin, F.; Xiang, L.; Deng, L.; Guan, Z.; Cui, W.; Zhang, H. Pharmaceutical electrospinning and 3D printing scaffold design for bone regeneration. Adv Drug Deliv Rev. 2021, 174, 504-534.
4. Zhao, C.; Liu, W.; Zhu, M.; Wu, C.; Zhu, Y. Bioceramic-based scaffolds with antibacterial function for bone tissue engineering: a review. Bioact Mater. 2022, 18, 383-398.
5. Zhi, W.; Wang, X.; Sun, D.; Chen, T.; Yuan, B.; Li, X.; Chen, X.; Wang, J.; Xie, Z.; Zhu, X.; Zhang, K.; Zhang, X. Optimal regenerative repair of large segmental bone defect in a goat model with osteoinductive calcium phosphate bioceramic implants. Bioact Mater. 2022, 11, 240-253.
6. Bai, L.; Song, P.; Su, J. Bioactive elements manipulate bone regeneration. Biomater Transl. 2023, 4, 248-269.
7. Li, B. Early immunomodulation by magnesium ion: catalyst for superior osteogenesis. Biomater Transl. 2023, 4, 294-296.
8. Díaz-Tocados, J. M.; Herencia, C.; Martínez-Moreno, J. M.; Montes de Oca, A.; Rodríguez-Ortiz, M. E.; Vergara, N.; Blanco, A.; Steppan, S.; Almadén, Y.; Rodríguez, M.; Muñoz-Castañeda, J. R. Magnesium Chloride promotes osteogenesis through Notch signaling activation and expansion of mesenchymal stem cells. Sci Rep. 2017, 7, 7839.
9. Nourisa, J.; Zeller-Plumhoff, B.; Helmholz, H.; Luthringer-Feyerabend, B.; Ivannikov, V.; Willumeit-Römer, R. Magnesium ions regulate mesenchymal stem cells population and osteogenic differentiation: A fuzzy agent-based modeling approach. Comput Struct Biotechnol J. 2021, 19, 4110-4122.
10. Qiao, W.; Wong, K. H. M.; Shen, J.; Wang, W.; Wu, J.; Li, J.; Lin, Z.; Chen, Z.; Matinlinna, J. P.; Zheng, Y.; Wu, S.; Liu, X.; Lai, K. P.; Chen, Z.; Lam, Y. W.; Cheung, K. M. C.; Yeung, K. W. K. TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration. Nat Commun. 2021, 12, 2885.
11. Castiglioni, S.; Cazzaniga, A.; Albisetti, W.; Maier, J. A. Magnesium and osteoporosis: current state of knowledge and future research directions. Nutrients. 2013, 5, 3022-3033.
12. Li, X.; Dai, B.; Guo, J.; Zhu, Y.; Xu, J.; Xu, S.; Yao, Z.; Chang, L.; Li, Y.; He, X.; Chow, D. H. K.; Zhang, S.; Yao, H.; Tong, W.; Ngai, T.; Qin, L. Biosynthesized bandages carrying magnesium oxide nanoparticles induce cortical bone formation by modulating endogenous periosteal cells. ACS Nano. 2022, 16, 18071-18089.
13. Maier, J. A.; Castiglioni, S.; Locatelli, L.; Zocchi, M.; Mazur, A. Magnesium and inflammation: Advances and perspectives. Semin Cell Dev Biol. 2021, 115, 37-44.
14. Bessa-Gonçalves, M.; Silva, A. M.; Brás, J. P.; Helmholz, H.; Luthringer-Feyerabend, B. J. C.; Willumeit-Römer, R.; Barbosa, M. A.; Santos, S. G. Fibrinogen and magnesium combination biomaterials modulate macrophage phenotype, NF-kB signaling and crosstalk with mesenchymal stem/stromal cells. Acta Biomater. 2020, 114, 471-484.
15. Zhang, J.; Tang, L.; Qi, H.; Zhao, Q.; Liu, Y.; Zhang, Y. Dual function of magnesium in bone biomineralization. Adv Healthc Mater. 2019, 8, e1901030.
16. Danks, A. E.; Hall, S. R.; Schnepp, Z. The evolution of ‘sol–gel’ chemistry as a technique for materials synthesis. Mater Horiz. 2016, 3, 91-112.
17. Peng, Z. D.; Yang, J. H.; Zhou, Z.; Liu, Y. X.; Li, Z. Q. Thermodynamic analysis on preparing doped zinc oxide varistor ceramic powders by coprecipitation process. Wuji Cailiao Xuebao. 1999, 14, 733-738.
18. Sōmiya, S. Hydrothermal preparation and sintering of fine ceramic powders. MRS Online Proc Libr. 1983, 24, 255-271.
19. Debuigne, F.; Jeunieau, L.; Wiame, M.; B.Nagy, J. Synthesis of organic nanoparticles in different W/O microemulsions. Langmuir. 2000, 16, 7605-7611.
20. Eslamian, M.; Ahmed, M.; Ashgriz, N. Modelling of nanoparticle formation during spray pyrolysis. Nanotechnology. 2006, 17, 1674-1685.
21. Eslamian, M.; Shekarriz, M. Recent advances in nanoparticle preparation by spray and micro-emulsion methods. Recent Pat Nanotechnol. 2009, 3, 99-115.
22. Brewster, J. H.; Kodas, T. T. Generation of unagglomerated, dense, BaTiO3 particles by flame-spray pyrolysis. AIChE J. 1997, 43, 2665-2669.
23. Deville, S.; Saiz, E.; Nalla, R. K.; Tomsia, A. P. Freezing as a path to build complex composites. Science. 2006, 311, 515-518.
24. Putra, N. E.; Borg, K. G. N.; Diaz-Payno, P. J.; Leeflang, M. A.; Klimopoulou, M.; Taheri, P.; Mol, J. M. C.; Fratila-Apachitei, L. E.; Huan, Z.; Chang, J.; Zhou, J.; Zadpoor, A. A. Additive manufacturing of bioactive and biodegradable porous iron-akermanite composites for bone regeneration. Acta Biomater. 2022, 148, 355-373.
25. Putra, N. E.; Leeflang, M. A.; Klimopoulou, M.; Dong, J.; Taheri, P.; Huan, Z.; Fratila-Apachitei, L. E.; Mol, J. M. C.; Chang, J.; Zhou, J.; Zadpoor, A. A. Extrusion-based 3D printing of biodegradable, osteogenic, paramagnetic, and porous FeMn-akermanite bone substitutes. Acta Biomater. 2023, 162, 182-198.
26. Canales, D. A.; Reyes, F.; Saavedra, M.; Peponi, L.; Leonés, A.; Palza, H.; Boccaccini, A. R.; Grünewald, A.; Zapata, P. A. Electrospun fibers of poly (lactic acid) containing bioactive glass and magnesium oxide nanoparticles for bone tissue regeneration. Int J Biol Macromol. 2022, 210, 324-336.
27. Chen, Y.; Sheng, W.; Lin, J.; Fang, C.; Deng, J.; Zhang, P.; Zhou, M.; Liu, P.; Weng, J.; Yu, F.; Wang, D.; Kang, B.; Zeng, H. Magnesium oxide nanoparticle coordinated phosphate-functionalized chitosan injectable hydrogel for osteogenesis and angiogenesis in bone regeneration. ACS Appl Mater Interfaces. 2022, 14, 7592-7608.
28. Zhao, X.; Wei, S.; Yang, Z.; Yang, P.; Liu, A. High-strength and tough bioactive Mg-doped hydroxyapatite bioceramics with oriented microchannels. Ceram Int. 2022, 48, 13494-13507.
29. Duda, G. N.; Geissler, S.; Checa, S.; Tsitsilonis, S.; Petersen, A.; Schmidt-Bleek, K. The decisive early phase of bone regeneration. Nat Rev Rheumatol. 2023, 19, 78-95.
30. Jang, J. W.; Min, K. E.; Kim, C.; Shin, J.; Lee, J.; Yi, S. Review: Scaffold characteristics, fabrication methods, and biomaterials for the bone tissue engineering. Int J Precis Eng Manuf. 2023, 24, 511-529.
31. Beattie, J. H.; Avenell, A. Trace element nutrition and bone metabolism. Nutr Res Rev. 1992, 5, 167-188.
32. Kanasan, N.; Adzila, S.; Koh, C. T.; Rahman, H. A.; Panerselvan, G. Effects of magnesium doping on the properties of hydroxyapatite/sodium alginate biocomposite. Adv Appl Ceram. 2019, 118, 381-386.
33. Tonelli, M.; Faralli, A.; Ridi, F.; Bonini, M. 3D printable magnesium-based cements towards the preparation of bioceramics. J Colloid Interface Sci. 2021, 598, 24-35.
34. Nabiyouni, M.; Brückner, T.; Zhou, H.; Gbureck, U.; Bhaduri, S. B. Magnesium-based bioceramics in orthopedic applications. Acta Biomater. 2018, 66, 23-43.
35. Luo, Y.; Wang, J.; Ong, M. T. Y.; Yung, P. S.; Wang, J.; Qin, L. Update on the research and development of magnesium-based biodegradable implants and their clinical translation in orthopaedics. Biomater Transl. 2021, 2, 188-196.
36. Trabelsi, M.; AlShahrani, I.; Algarni, H.; Ben Ayed, F.; Yousef, E. S. Mechanical and tribological properties of the tricalcium phosphate - magnesium oxide composites. Mater Sci Eng C Mater Biol Appl. 2019, 96, 716-729.
37. Sikder, P.; Ren, Y.; Bhaduri, S. B. Microwave processing of calcium phosphate and magnesium phosphate based orthopedic bioceramics: A state-of-the-art review. Acta Biomater. 2020, 111, 29-53.
38. George, S. M.; Nayak, C.; Singh, I.; Balani, K. Multifunctional hydroxyapatite composites for orthopedic applications: a review. ACS Biomater Sci Eng. 2022, 8, 3162-3186.
39. Ullah, I.; Gloria, A.; Zhang, W.; Ullah, M. W.; Wu, B.; Li, W.; Domingos, M.; Zhang, X. Synthesis and characterization of sintered Sr/Fe-modified hydroxyapatite bioceramics for bone tissue engineering applications. ACS Biomater Sci Eng. 2020, 6, 375-388.
40. Zhao, X.; Yang, Z.; Liu, Q.; Yang, P.; Wang, P.; Wei, S.; Liu, A.; Zhao, Z. Potential load-bearing bone substitution material: carbon-fiber-reinforced magnesium-doped hydroxyapatite composites with excellent mechanical performance and tailored biological properties. ACS Biomater Sci Eng. 2022, 8, 921-938.
41. Coelho, C. C.; Padrão, T.; Costa, L.; Pinto, M. T.; Costa, P. C.; Domingues, V. F.; Quadros, P. A.; Monteiro, F. J.; Sousa, S. R. The antibacterial and angiogenic effect of magnesium oxide in a hydroxyapatite bone substitute. Sci Rep. 2020, 10, 19098.
42. Coelho, C. C.; Araújo, R.; Quadros, P. A.; Sousa, S. R.; Monteiro, F. J. Antibacterial bone substitute of hydroxyapatite and magnesium oxide to prevent dental and orthopaedic infections. Mater Sci Eng C Mater Biol Appl. 2019, 97, 529-538.
43. Ballouze, R.; Marahat, M. H.; Mohamad, S.; Saidin, N. A.; Kasim, S. R.; Ooi, J. P. Biocompatible magnesium-doped biphasic calcium phosphate for bone regeneration. J Biomed Mater Res B Appl Biomater. 2021, 109, 1426-1435.
44. Frasnelli, M.; Sglavo, V. M. Effect of Mg(2+) doping on beta-alpha phase transition in tricalcium phosphate (TCP) bioceramics. Acta Biomater. 2016, 33, 283-289.
45. He, F.; Rao, J.; Zhou, J.; Fu, W.; Wang, Y.; Zhang, Y.; Zuo, F.; Shi, H. Fabrication of 3D printed Ca(3)Mg(3)(PO(4))(4)-based bioceramic scaffolds with tailorable high mechanical strength and osteostimulation effect. Colloids Surf B Biointerfaces. 2023, 229, 113472.
46. Ge, M.; Xie, D.; Yang, Y.; Tian, Z. Sintering densification mechanism and mechanical properties of the 3D-printed high-melting-point-difference magnesium oxide/calcium phosphate composite bio-ceramic scaffold. J Mech Behav Biomed Mater. 2023, 144, 105978.
47. Zhang, Y.; Lin, T.; Meng, H.; Wang, X.; Peng, H.; Liu, G.; Wei, S.; Lu, Q.; Wang, Y.; Wang, A.; Xu, W.; Shao, H.; Peng, J. 3D gel-printed porous magnesium scaffold coated with dibasic calcium phosphate dihydrate for bone repair in vivo. J Orthop Translat. 2022, 33, 13-23.
48. Cao, X.; Zhu, J.; Zhang, C.; Xian, J.; Li, M.; Nath Varma, S.; Qin, Z.; Deng, Q.; Zhang, X.; Yang, W.; Liu, C. Magnesium-rich calcium phosphate derived from tilapia bone has superior osteogenic potential. J Funct Biomater. 2023, 14, 390.
49. Wu, F.; Su, J.; Wei, J.; Guo, H.; Liu, C. Injectable bioactive calcium-magnesium phosphate cement for bone regeneration. Biomed Mater. 2008, 3, 044105.
50. Karfarma, M.; Esnaashary, M. H.; Rezaie, H. R.; Javadpour, J.; Naimi-Jamal, M. R. Poly(propylene fumarate)/magnesium calcium phosphate injectable bone composite: effect of filler size and its weight fraction on mechanical properties. Proc Inst Mech Eng H. 2019, 233, 1165-1174.
51. Wu, J.; Liu, F.; Wang, Z.; Liu, Y.; Zhao, X.; Fang, C.; Leung, F.; Yeung, K. W. K.; Wong, T. M. The development of a magnesium-releasing and long-term mechanically stable calcium phosphate bone cement possessing osteogenic and immunomodulation effects for promoting bone fracture regeneration. Front Bioeng Biotechnol. 2021, 9, 803723.
52. Wu, X.; Dai, H.; Yu, S.; Zhao, Y.; Long, Y.; Li, W.; Tu, J. Magnesium calcium phosphate cement incorporating citrate for vascularized bone regeneration. ACS Biomater Sci Eng. 2020, 6, 6299-6308.
53. Kanter, B.; Vikman, A.; Brückner, T.; Schamel, M.; Gbureck, U.; Ignatius, A. Bone regeneration capacity of magnesium phosphate cements in a large animal model. Acta Biomater. 2018, 69, 352-361.
54. Kaiser, F.; Schröter, L.; Stein, S.; Krüger, B.; Weichhold, J.; Stahlhut, P.; Ignatius, A.; Gbureck, U. Accelerated bone regeneration through rational design of magnesium phosphate cements. Acta Biomater. 2022, 145, 358-371.
55. Brückner, T.; Meininger, M.; Groll, J.; Kübler, A. C.; Gbureck, U. Magnesium phosphate cement as mineral bone adhesive. Materials (Basel). 2019, 12, 3819.
56. Azeena, S.; Subhapradha, N.; Selvamurugan, N.; Narayan, S.; Srinivasan, N.; Murugesan, R.; Chung, T. W.; Moorthi, A. Antibacterial activity of agricultural waste derived wollastonite doped with copper for bone tissue engineering. Mater Sci Eng C Mater Biol Appl. 2017, 71, 1156-1165.
57. Namdar, A.; Salahinejad, E. Advances in ion-doping of Ca-Mg silicate bioceramics for bone tissue engineering. Coord Chem Rev. 2023, 478, 215001.
58. Bavya Devi, K.; Nandi, S. K.; Roy, M. Magnesium silicate bioceramics for bone regeneration: a review. J Indian Inst Sci. 2019, 99, 261-288.
59. Huang, Y.; Jin, X.; Zhang, X.; Sun, H.; Tu, J.; Tang, T.; Chang, J.; Dai, K. In vitro and in vivo evaluation of akermanite bioceramics for bone regeneration. Biomaterials. 2009, 30, 5041-5048.
60. Xia, L.; Yin, Z.; Mao, L.; Wang, X.; Liu, J.; Jiang, X.; Zhang, Z.; Lin, K.; Chang, J.; Fang, B. Akermanite bioceramics promote osteogenesis, angiogenesis and suppress osteoclastogenesis for osteoporotic bone regeneration. Sci Rep. 2016, 6, 22005.
61. Qi, L.; Fang, X.; Yan, J.; Pan, C.; Ge, W.; Wang, J.; Shen, S. G.; Lin, K.; Zhang, L. Magnesium-containing bioceramics stimulate exosomal miR-196a-5p secretion to promote senescent osteogenesis through targeting Hoxa7/MAPK signaling axis. Bioact Mater. 2024, 33, 14-29.
62. Saran, U.; Gemini Piperni, S.; Chatterjee, S. Role of angiogenesis in bone repair. Arch Biochem Biophys. 2014, 561, 109-117.
63. Zhai, W.; Lu, H.; Chen, L.; Lin, X.; Huang, Y.; Dai, K.; Naoki, K.; Chen, G.; Chang, J. Silicate bioceramics induce angiogenesis during bone regeneration. Acta Biomater. 2012, 8, 341-349.
64. Mayr-Wohlfart, U.; Waltenberger, J.; Hausser, H.; Kessler, S.; Günther, K. P.; Dehio, C.; Puhl, W.; Brenner, R. E. Vascular endothelial growth factor stimulates chemotactic migration of primary human osteoblasts. Bone. 2002, 30, 472-477.
65. Diba, M.; Goudouri, O. M.; Tapia, F.; Boccaccini, A. R. Magnesium-containing bioactive polycrystalline silicate-based ceramics and glass-ceramics for biomedical applications. Curr Opin Solid State Mater Sci. 2014, 18, 147-167.
66. Winet, H. The role of microvasculature in normal and perturbed bone healing as revealed by intravital microscopy. Bone. 1996, 19, 39S-57S.
67. Yi, D.; Wu, C.; Ma, X.; Ji, H.; Zheng, X.; Chang, J. Preparation and in vitro evaluation of plasma-sprayed bioactive akermanite coatings. Biomed Mater. 2012, 7, 065004.
68. Kharaziha, M.; Fathi, M. H. Synthesis and characterization of bioactive forsterite nanopowder. Ceram Int. 2009, 35, 2449-2454.
69. Ni, S.; Chang, J.; Chou, L. In vitro studies of novel CaO-SiO2-MgO system composite bioceramics. J Mater Sci Mater Med. 2008, 19, 359-367.
70. Fathi, M. H.; Kharaziha, M. Two-step sintering of dense, nanostructural forsterite. Mater Lett. 2009, 63, 1455-1458.
71. Kharaziha, M.; Fathi, M. H. Improvement of mechanical properties and biocompatibility of forsterite bioceramic addressed to bone tissue engineering materials. J Mech Behav Biomed Mater. 2010, 3, 530-537.
72. Naghiu, M. A.; Gorea, M.; Mutch, E.; Kristaly, F.; Tomoaia-Cotisel, M. Forsterite nanopowder: structural characterization and biocompatibility evaluation. J Mater Sci Technol. 2013, 29, 628-632.
73. Devi, K. B.; Tripathy, B.; Kumta, P. N.; Nandi, S. K.; Roy, M. In vivo biocompatibility of zinc-doped magnesium silicate bio-ceramics. ACS Biomater Sci Eng. 2018, 4, 2126-2133.
74. Devi, K. B.; Tripathy, B.; Roy, A.; Lee, B.; Kumta, P. N.; Nandi, S. K.; Roy, M. In vitro biodegradation and in vivo biocompatibility of forsterite bio-ceramics: effects of strontium substitution. ACS Biomater Sci Eng. 2019, 5, 530-543.
75. Choudhary, R.; Chatterjee, A.; Venkatraman, S. K.; Koppala, S.; Abraham, J.; Swamiappan, S. Antibacterial forsterite (Mg(2)SiO(4)) scaffold: A promising bioceramic for load bearing applications. Bioact Mater. 2018, 3, 218-224.
76. Xie, Y.; Zhai, W.; Chen, L.; Chang, J.; Zheng, X.; Ding, C. Preparation and in vitro evaluation of plasma-sprayed Mg(2)SiO(4) coating on titanium alloy. Acta Biomater. 2009, 5, 2331-2337.
77. Rizwan, M.; Hamdi, M.; Basirun, W. J. Bioglass® 45S5-based composites for bone tissue engineering and functional applications. J Biomed Mater Res A. 2017, 105, 3197-3223.
78. Lalzawmliana, V.; Anand, A.; Roy, M.; Kundu, B.; Nandi, S. K. Mesoporous bioactive glasses for bone healing and biomolecules delivery. Mater Sci Eng C Mater Biol Appl. 2020, 106, 110180.
79. Thanigachalam, M.; Subramanian, A. V. M. Fabrication, microstructure and properties of advanced ceramic-reinforced composites for dental implants: a review. Biomater Transl. 2023, 4, 151-165.
80. Sivakumar, P. M.; Yetisgin, A. A.; Demir, E.; Sahin, S. B.; Cetinel, S. Polysaccharide-bioceramic composites for bone tissue engineering: A review. Int J Biol Macromol. 2023, 250, 126237.
81. Bellucci, D.; Cannillo, V.; Anesi, A.; Salvatori, R.; Chiarini, L.; Manfredini, T.; Zaffe, D. Bone regeneration by novel bioactive glasses containing strontium and/or magnesium: a preliminary in-vivo study. Materials (Basel). 2018, 11, 2223.
82. Verné, E.; Bretcanu, O.; Balagna, C.; Bianchi, C. L.; Cannas, M.; Gatti, S.; Vitale-Brovarone, C. Early stage reactivity and in vitro behavior of silica-based bioactive glasses and glass-ceramics. J Mater Sci Mater Med. 2009, 20, 75-87.
83. Diba, M.; Tapia, F.; Boccaccini, A. R.; Strobel, L. A. Magnesium-containing bioactive glasses for biomedical applications. Int J Appl Glass Sci. 2012, 3, 221-253.
84. Oliveira, J. M.; Correia, R. N.; Fernandes, M. H. Effects of Si speciation on the in vitro bioactivity of glasses. Biomaterials. 2002, 23, 371-379.
85. Magallanes-Perdomo, M.; De Aza, A. H.; Sobrados, I.; Sanz, J.; Pena, P. Structure and properties of bioactive eutectic glasses based on the Ca3(PO4)2-CaSiO3-CaMg(SiO3)2 system. Acta Biomater. 2012, 8, 820-829.
86. Hand, R. J.; Tadjiev, D. R. Mechanical properties of silicate glasses as a function of composition. J Non Cryst Solids 2010, 356, 2417-2423.
87. Zheng, Q.; Potuzak, M.; Mauro, J. C.; Smedskjaer, M. M.; Youngman, R. E.; Yue, Y. Composition–structure–property relationships in boroaluminosilicate glasses. J Non Cryst Solids. 2012, 358, 993-1002.
88. Chen, X.; Ou, J.; Wei, Y.; Huang, Z.; Kang, Y.; Yin, G. Effect of MgO contents on the mechanical properties and biological performances of bioceramics in the MgO-CaO-SiO2 system. J Mater Sci Mater Med. 2010, 21, 1463-1471.
89. Yang, S.; Liang, L.; Liu, L.; Yin, Y.; Liu, Y.; Lei, G.; Zhou, K.; Huang, Q.; Wu, H. Using MgO nanoparticles as a potential platform to precisely load and steadily release Ag ions for enhanced osteogenesis and bacterial killing. Mater Sci Eng C Mater Biol Appl. 2021, 119, 111399.
90. Alinda Shaly, A.; Hannah Priya, G.; Mahendiran, M.; Mary Linet, J. A behavioural study of hydrothermally derived novel alumina/magnesia/hydroxyapatite (Al(2)O(3)/MgO/HA) bioceramic nanocomposite. J Mech Behav Biomed Mater. 2022, 133, 105313.
91. Hao, L.; Lawrence, J.; Chian, K. S. Effects of CO2 laser irradiation on the surface properties of magnesia-partially stabilised zirconia (MgO-PSZ) bioceramic and the subsequent improvements in human osteoblast cell adhesion. J Biomater Appl. 2004, 19, 81-105.
92. Lengyel, J. S.; Milne, J. L.; Subramaniam, S. Electron tomography in nanoparticle imaging and analysis. Nanomedicine (Lond). 2008, 3, 125-131.
93. Nandi, S. K.; Roy, M.; Bandyopadhyay, A.; Bose, S. In vivo biocompatibility of SrO and MgO doped brushite cements. J Biomed Mater Res B Appl Biomater. 2023, 111, 599-609.
94. Li, C.; Sun, J.; Shi, K.; Long, J.; Li, L.; Lai, Y.; Qin, L. Preparation and evaluation of osteogenic nano-MgO/PMMA bone cement for bone healing in a rat critical size calvarial defect. J Mater Chem B. 2020, 8, 4575-4586.
95. Ke, D.; Tarafder, S.; Vahabzadeh, S.; Bose, S. Effects of MgO, ZnO, SrO, and SiO(2) in tricalcium phosphate scaffolds on in vitro gene expression and in vivo osteogenesis. Mater Sci Eng C Mater Biol Appl. 2019, 96, 10-19.
96. Chen, R.; Chen, H. B.; Xue, P. P.; Yang, W. G.; Luo, L. Z.; Tong, M. Q.; Zhong, B.; Xu, H. L.; Zhao, Y. Z.; Yuan, J. D. HA/MgO nanocrystal-based hybrid hydrogel with high mechanical strength and osteoinductive potential for bone reconstruction in diabetic rats. J Mater Chem B. 2021, 9, 1107-1122.
97. Yuan, B.; Chen, H.; Zhao, R.; Deng, X.; Chen, G.; Yang, X.; Xiao, Z.; Aurora, A.; Iulia, B. A.; Zhang, K.; Zhu, X.; Iulian, A. V.; Hai, S.; Zhang, X. Construction of a magnesium hydroxide/graphene oxide/hydroxyapatite composite coating on Mg-Ca-Zn-Ag alloy to inhibit bacterial infection and promote bone regeneration. Bioact Mater. 2022, 18, 354-367.
98. Wang, G.; Jiang, W.; Mo, S.; Xie, L.; Liao, Q.; Hu, L.; Ruan, Q.; Tang, K.; Mehrjou, B.; Liu, M.; Tong, L.; Wang, H.; Zhuang, J.; Wu, G.; Chu, P. K. Nonleaching antibacterial concept demonstrated by in situ construction of 2D nanoflakes on magnesium. Adv Sci (Weinh). 2020, 7, 1902089.
99. Janning, C.; Willbold, E.; Vogt, C.; Nellesen, J.; Meyer-Lindenberg, A.; Windhagen, H.; Thorey, F.; Witte, F. Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the osteoclast number in peri-implant bone remodelling. Acta Biomater. 2010, 6, 1861-1868.
100. Pinho, L. C.; Alves, M. M.; Colaço, B.; Fernandes, M. H.; Santos, C. Green-synthesized magnesium hydroxide nanoparticles induced osteoblastic differentiation in bone co-cultured cells. Pharmaceuticals (Basel). 2021, 14, 1281.
101. Shive, M. S.; Anderson, J. M. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev. 1997, 28, 5-24.
102. Niiranen, H.; Pyhältö, T.; Rokkanen, P.; Kellomäki, M.; Törmälä, P. In vitro and in vivo behavior of self-reinforced bioabsorbable polymer and self-reinforced bioabsorbable polymer/bioactive glass composites. J Biomed Mater Res A. 2004, 69, 699-708.
103. Wang, X.; Liu, M.; Li, H.; Yin, A.; Xia, C.; Lou, X.; Wang, H.; Mo, X.; Wu, J. MgO-incorporated porous nanofibrous scaffold promotes osteogenic differentiation of pre-osteoblasts. Mater Lett. 2021, 299, 130098.
104. Ji, J.; Dong, X.; Ma, X.; Tang, S.; Wu, Z.; Xia, J.; Wang, Q.; Wang, Y.; Wei, J. Preparation and characterization of bioactive and degradable composites containing ordered mesoporous calcium-magnesium silicate and poly(l-lactide). Appl Surf Sci. 2014, 317, 1090-1099.
105. Wang, C.; Meng, C.; Zhang, Z.; Zhu, Q. 3D printing of polycaprolactone/bioactive glass composite scaffolds for in situ bone repair. Ceram Int. 2022, 48, 7491-7499.
106. Niknam, Z.; Golchin, A.; Rezaei-Tavirani, M.; Ranjbarvan, P.; Zali, H.; Omidi, M.; Mansouri, V. Osteogenic differentiation potential of adipose-derived mesenchymal stem cells cultured on magnesium oxide/polycaprolactone nanofibrous scaffolds for improving bone tissue reconstruction. Adv Pharm Bull. 2022, 12, 142-154.
107. Salaris, V.; Leonés, A.; López, D.; Kenny, J. M.; Peponi, L. A comparative study on the addition of MgO and Mg(OH)2 nanoparticles into PCL electrospun fibers. Macromol Chem Phys. 2023, 224, 2200215.
108. Vidhya, E.; Vijayakumar, S.; Nilavukkarasi, M.; Punitha, V. N.; Snega, S.; Praseetha, P. K. Green fabricated MgO nanoparticles as antimicrobial agent: characterization and evaluation. Mater Today Proc. 2021, 45, 5579-5583.
109. Dong, Y.; Yao, L.; Cai, L.; Jin, M.; Forouzanfar, T.; Wu, L.; Liu, J.; Wu, G. Antimicrobial and pro-osteogenic coaxially electrospun magnesium oxide nanoparticles-polycaprolactone/parathyroid hormone-polycaprolactone composite barrier membrane for guided bone regeneration. Int J Nanomedicine. 2023, 18, 369-383.
110. Fan, L.; Chen, S.; Yang, M.; Liu, Y.; Liu, J. Metallic materials for bone repair. Adv Healthc Mater. 2024, 13, e2302132.
111. Alipour, S.; Nour, S.; Attari, S. M.; Mohajeri, M.; Kianersi, S.; Taromian, F.; Khalkhali, M.; Aninwene, G. E., 2nd; Tayebi, L. A review on in vitro/in vivo response of additively manufactured Ti-6Al-4V alloy. J Mater Chem B. 2022, 10, 9479-9534.
112. Rondanelli, M.; Faliva, M. A.; Tartara, A.; Gasparri, C.; Perna, S.; Infantino, V.; Riva, A.; Petrangolini, G.; Peroni, G. An update on magnesium and bone health. Biometals. 2021, 34, 715-736.
113. Dorozhkin, S. V. Calcium orthophosphate bioceramics. Ceram Int. 2015, 41, 13913-13966.
114. Wu, C.; Chang, J. A review of bioactive silicate ceramics. Biomed Mater. 2013, 8, 032001.
115. Zhang, M.; Yang, N.; Dehghan-Manshadi, A.; Venezuela, J.; Bermingham, M. J.; Dargusch, M. S. Fabrication and properties of biodegradable akermanite-reinforced Fe35Mn alloys for temporary orthopedic implant applications. ACS Biomater Sci Eng. 2023, 9, 1261-1273.
116. Siahmard, P.; Amini Najafabadi, R.; Meysami, A.; Meysami, M.; Isfahani, T. Investigation of structural properties of forsterite coating on AZ91 magnesium alloy by sol-gel method. Results Eng. 2023, 18, 101138.
117. Bose, S.; Roy, M.; Bandyopadhyay, A. Recent advances in bone tissue engineering scaffolds. Trends Biotechnol. 2012, 30, 546-554.
118. Lewns, F. K.; Tsigkou, O.; Cox, L. R.; Wildman, R. D.; Grover, L. M.; Poologasundarampillai, G. Hydrogels and bioprinting in bone tissue engineering: creating artificial stem-cell niches for in vitro models. Adv Mater. 2023, 35, e2301670.
119. Sarian, M. N.; Iqbal, N.; Sotoudehbagha, P.; Razavi, M.; Ahmed, Q. U.; Sukotjo, C.; Hermawan, H. Potential bioactive coating system for high-performance absorbable magnesium bone implants. Bioact Mater. 2022, 12, 42-63.
120. El-Rashidy, A. A.; Roether, J. A.; Harhaus, L.; Kneser, U.; Boccaccini, A. R. Regenerating bone with bioactive glass scaffolds: a review of in vivo studies in bone defect models. Acta Biomater. 2017, 62, 1-28.
121. Liu, X.; Liu, Y.; Qiang, L.; Ren, Y.; Lin, Y.; Li, H.; Chen, Q.; Gao, S.; Yang, X.; Zhang, C.; Fan, M.; Zheng, P.; Li, S.; Wang, J. Multifunctional 3D-printed bioceramic scaffolds: recent strategies for osteosarcoma treatment. J Tissue Eng. 2023, 14, 20417314231170371.
122. Ma, H.; Feng, C.; Chang, J.; Wu, C. 3D-printed bioceramic scaffolds: from bone tissue engineering to tumor therapy. Acta Biomater. 2018, 79, 37-59.
123. McWilliam, R. H.; Chang, W.; Liu, Z.; Wang, J.; Han, F.; Black, R. A.; Wu, J.; Luo, X.; Li, B.; Shu, W. Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds. Biomater Transl. 2023, 4, 104-114.
124. He, F.; Yuan, X.; Lu, T.; Wang, Y.; Feng, S.; Shi, X.; Wang, L.; Ye, J.; Yang, H. Preparation and characterization of novel lithium magnesium phosphate bioceramic scaffolds facilitating bone generation. J Mater Chem B. 2022, 10, 4040-4047.
125. Mouriño, V.; Boccaccini, A. R. Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. J R Soc Interface. 2010, 7, 209-227.
126. Alegrete, N.; Sousa, S. R.; Peleteiro, B.; Monteiro, F. J.; Gutierres, M. Local antibiotic delivery ceramic bone substitutes for the treatment of infected bone cavities and bone regeneration: a systematic review on what we have learned from animal models. Materials (Basel). 2023, 16, 2387.
127. Radwan, N. H.; Nasr, M.; Ishak, R. A. H.; Awad, G. A. S. Moxifloxacin-loaded in situ synthesized bioceramic/poly(L-lactide-co-ε-caprolactone) composite scaffolds for treatment of osteomyelitis and orthopedic regeneration. Int J Pharm. 2021, 602, 120662.
128. Soundrapandian, C.; Datta, S.; Kundu, B.; Basu, D.; Sa, B. Porous bioactive glass scaffolds for local drug delivery in osteomyelitis: development and in vitro characterization. AAPS PharmSciTech. 2010, 11, 1675-1683.
129. Kundu, B.; Soundrapandian, C.; Nandi, S. K.; Mukherjee, P.; Dandapat, N.; Roy, S.; Datta, B. K.; Mandal, T. K.; Basu, D.; Bhattacharya, R. N. Development of new localized drug delivery system based on ceftriaxone-sulbactam composite drug impregnated porous hydroxyapatite: a systematic approach for in vitro and in vivo animal trial. Pharm Res. 2010, 27, 1659-1676.
130. Soundrapandian, C.; Basu, D.; Sa, B.; Datta, S. Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation. Drug Dev Ind Pharm. 2011, 37, 538-546.
131. Thanyaphoo, S.; Kaewsrichan, J. Synthesis and evaluation of novel glass ceramics as drug delivery systems in osteomyelitis. J Pharm Sci. 2012, 101, 2870-2882.
132. Deng, C.; Zhou, Q.; Zhang, M.; Li, T.; Chen, H.; Xu, C.; Feng, Q.; Wang, X.; Yin, F.; Cheng, Y.; Wu, C. Bioceramic scaffolds with antioxidative functions for ROS scavenging and osteochondral regeneration. Adv Sci (Weinh). 2022, 9, e2105727.
133. Zhao, Z.; Li, G.; Ruan, H.; Chen, K.; Cai, Z.; Lu, G.; Li, R.; Deng, L.; Cai, M.; Cui, W. Capturing magnesium ions via microfluidic hydrogel microspheres for promoting cancellous bone regeneration. ACS Nano. 2021, 15, 13041-13054.
134. Zhang, X.; Zhu, Y.; Cao, L.; Wang, X.; Zheng, A.; Chang, J.; Wu, J.; Wen, J.; Jiang, X.; Li, H.; Zhang, Z. Alginate-aker injectable composite hydrogels promoted irregular bone regeneration through stem cell recruitment and osteogenic differentiation. J Mater Chem B. 2018, 6, 1951-1964.
135. Ostrowski, N.; Roy, A.; Kumta, P. N. Magnesium phosphate cement systems for hard tissue applications: a review. ACS Biomater Sci Eng. 2016, 2, 1067-1083.
136. Hu, J.; Shao, J.; Huang, G.; Zhang, J.; Pan, S. In vitro and in vivo applications of magnesium-enriched biomaterials for vascularized osteogenesis in bone tissue engineering: a review of literature. J Funct Biomater. 2023, 14, 326.
137. Yu, Y.; Wang, J.; Liu, C.; Zhang, B.; Chen, H.; Guo, H.; Zhong, G.; Qu, W.; Jiang, S.; Huang, H. Evaluation of inherent toxicology and biocompatibility of magnesium phosphate bone cement. Colloids Surf B Biointerfaces. 2010, 76, 496-504.
138. Wu, F.; Wei, J.; Guo, H.; Chen, F.; Hong, H.; Liu, C. Self-setting bioactive calcium-magnesium phosphate cement with high strength and degradability for bone regeneration. Acta Biomater. 2008, 4, 1873-1884.
139. Cabrejos-Azama, J.; Alkhraisat, M. H.; Rueda, C.; Torres, J.; Pintado, C.; Blanco, L.; López-Cabarcos, E. Magnesium substitution in brushite cements: Efficacy of a new biomaterial loaded with vancomycin for the treatment of Staphylococcus aureus infections. Mater Sci Eng C Mater Biol Appl. 2016, 61, 72-78.
140. Mestres, G.; Ginebra, M. P. Novel magnesium phosphate cements with high early strength and antibacterial properties. Acta Biomater. 2011, 7, 1853-1861.
141. Mestres, G.; Abdolhosseini, M.; Bowles, W.; Huang, S. H.; Aparicio, C.; Gorr, S. U.; Ginebra, M. P. Antimicrobial properties and dentin bonding strength of magnesium phosphate cements. Acta Biomater. 2013, 9, 8384-8393.
142. Lin, Z.; Wu, J.; Qiao, W.; Zhao, Y.; Wong, K. H. M.; Chu, P. K.; Bian, L.; Wu, S.; Zheng, Y.; Cheung, K. M. C.; Leung, F.; Yeung, K. W. K. Precisely controlled delivery of magnesium ions thru sponge-like monodisperse PLGA/nano-MgO-alginate core-shell microsphere device to enable in-situ bone regeneration. Biomaterials. 2018, 174, 1-16.
143. Liu, C.; Yang, G.; Zhou, M.; Zhang, X.; Wu, X.; Wu, P.; Gu, X.; Jiang, X. Magnesium ammonium phosphate composite cell-laden hydrogel promotes osteogenesis and angiogenesis in vitro. ACS Omega. 2021, 6, 9449-9459.
144. Zhu, Y.; Deng, S.; Ma, Z.; Kong, L.; Li, H.; Chan, H. F. Macrophages activated by akermanite/alginate composite hydrogel stimulate migration of bone marrow-derived mesenchymal stem cells. Biomed Mater. 2021, 16, 045004.
145. Wang, J. L.; Xu, J. K.; Hopkins, C.; Chow, D. H.; Qin, L. Biodegradable magnesium-based implants in orthopedics-a general review and perspectives. Adv Sci (Weinh). 2020, 7, 1902443.
146. Tao, Z. S.; Zhou, W. S.; He, X. W.; Liu, W.; Bai, B. L.; Zhou, Q.; Huang, Z. L.; Tu, K. K.; Li, H.; Sun, T.; Lv, Y. X.; Cui, W.; Yang, L. A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C Mater Biol Appl. 2016, 62, 226-232.
147. Varshney, S.; Nigam, A.; Singh, A.; Samanta, S. K.; Mishra, N.; Tewari, R. P. Antibacterial, structural, and mechanical properties of MgO/ZnO nanocomposites and its HA-based bio-ceramics; synthesized via physio-chemical route for biomedical applications. Mater Technol. 2022, 37, 2503-2516.
148. Cui, J.; Xia, L.; Lin, K.; Wang, X. In situ construction of a nano-structured akermanite coating for promoting bone formation and osseointegration of Ti-6Al-4V implants in a rabbit osteoporosis model. J Mater Chem B. 2021, 9, 9505-9513.
