journal article·2019-12Open access

Mg/Cu co-substituted hydroxyapatite – Biocompatibility, mechanical properties and antimicrobial activity

Djordje Veljovic, Tamara Matic, Tanja Stamenic, Vesna Kojic, Suzana Dimitrijevic-Brankovic, Miodrag J. Lukic, Sanja Jevtic, Zeljko Radovanovic, Rada Petrovic, Djordje Janackovic

Ceramics International· Volume 45· Issue 17

Abstract

The aim of this study was to improve the mechanical properties and to optimize antimicrobial activity of hydroxyapatite (HAP) by simultaneous doping with Mg and Cu ions in order to obtain material that would be able to assist in the bone/tooth healing process, prevent post-implementation infections and provide satisfying values of hardness and fracture toughness for biomedical application. Ion doping was done during the hydrothermal synthesis of HAP powders, whereby the content of Mg ions in the starting solution was varied between 1-20 mol. % with regard to Ca ions, while the amount of Cu ions was kept constant at 0.4 mol. %. The green compacts were sintered for 2 h at temperatures ranging 750–1200 °C depending on the Mg content, chosen in agreement with dilatometry results. Presence of Mg ions was found to favour transition from HAP to β−tricalcium phosphate phase (β−TCP), which enabled formation of biphasic HAP/β−TCP and pure β−TCP phase at 160 °C during hydrothermal synthesis. In vitro investigation of antimicrobial activity against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis showed satisfactory antimicrobial activity. MTT assay performed on MRC-5 and L929 cell lines showed excellent cytocompatibility and cell proliferation. Maximum hardness by Vickers and fracture toughness values, 4.96 GPa and 1.75 MPa m1/2 respectively, were obtained upon addition of 5 mol. % Mg, as a consequence of the lowest grain size and porosity, as well as the highest densification rate. This is, to the best of our knowledge, the highest fracture toughness for HAP or β-TCP ceramics reported thus far.
Source: openaire · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Bone Tissue Engineering Materials · Dental Implant Techniques and Outcomes · Dental materials and restorations

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (61)

Show source-provided references
1. Calcium orthophosphate bioceramics10.1016/j.ceramint.2015.08.004 ↗
2. Novel apatite-based sorbent for defluoridation: synthesis and sorption characteristics of nanomicrocrystalline Hydroxyapatite-Coated-Limestone10.1021/es405135r ↗
3. The effect of grain size on the biocompatibility, cell-materials interface and mechanical properties of microwave-sintered bioceramics10.1002/jbm.a.34225 ↗
4. Experimental design of plasma spraying and laser treatment of hydroxyapatite coatings10.1016/j.surfcoat.2006.04.055 ↗
5. Composition, structure and mechanical properties of the titanium surface after induction heat treatment followed by modification with hydroxyapatite nanoparticles10.1016/j.ceramint.2016.03.213 ↗
6. Structure and mechanical properties of hydroxyapatite coatings produced on titanium using plasma spraying with induction preheating10.1016/j.ceramint.2017.05.168 ↗
7. Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis: I. Preparation and Drug Release10.1002/jbm.a.34426 ↗
8. Calcium phosphate system for gene delivery: historical background and emerging opportunities10.2174/1381612822666151210123859 ↗
9. Substituted hydroxyapatites for biomedical applications: a review10.1016/j.ceramint.2015.03.316 ↗
10. Self-setting calcium phosphate cements with tunable antibiotic release rates for advanced bone graft applications10.1021/acsami.6b01160 ↗
11. Porous microspheres of magnesium witlockite and amorphous calcium magnesium phosphate: microwave-assisted rapid synthesis using creatine phosphate, and application in drug delivery10.1039/C5TB01106J ↗
12. Influence of magnesium substitution on a collagen-apatite biomaterial on the production of a calcifying matrix by human osteoblasts10.1002/(SICI)1097-4636(19981215)42:4<626::AID-JBM20>3.0.CO;2-S ↗
13. Biomimetic Mg- and Mg, CO3- substituted hydroxyapatites: synthesis characterization and in vitro behaviour10.1016/j.jeurceramsoc.2005.06.040 ↗
14. Biomimetic Mg substituted hydroxyapatite: from synthesis to in vivo behaviour10.1007/s10856-006-0032-y ↗
15. Effect of doping (Mg,Mn,Zn) on the microstructure and mechanical properties of spark plasma sintered hydroxyapatites synthesized by mechanical alloying10.1016/j.ceramint.2016.11.027 ↗
16. Mg-substituted hydroxyapatite nanopowders: synthesis, thermal stability and sintering behaviour10.1016/j.jeurceramsoc.2009.04.038 ↗
17. Synthesis and structure of magnesium-substituted hydroxyapatite10.1023/A:1025509305805 ↗
18. Synthesis and thermal behavior of Mg-doped calcium phosphate nanopowders via the sol gel method10.1016/j.scient.2011.11.014 ↗
19. Copper(II), zinc(II) and copper(II)/zinc(II)-containing carbonate-substituted hydroxyapatite: synthesis, characterization and thermal behaviour10.1002/mawe.201600460 ↗
20. Antimicrobial activity and biocompatibility of Ag+- and Cu2+ -doped biphasic hydroxyapatite/-tricalcium phosphate obtained from hydrothermally synthesized Ag+- and Cu2+-doped hydroxyapatite10.1016/j.apsusc.2014.04.066 ↗
21. Pharmacology and toxicology of heavy metals: silver
22. Copper as a biocidal tool10.2174/0929867054637617 ↗
23. Copper and boron as examples of dietary trace elements important in bone development and disease10.1097/00001433-199810000-00006 ↗
24. Role of copper in collagen cross-linking and its influence on selected mechanical properties of chick bone and tendon10.1093/jn/112.4.708 ↗
25. Composite nanostructured hydroxyapatite/yttrium stabilized zirconia dental inserts – the processing and application as dentin substitutes10.1016/j.ceramint.2018.07.028 ↗
26. The effect of calcinated hydroxyapatite and magnesium doped hydroxyapatite as fillers on the mechanical properties of a model BisGMA/TEGDMA dental composite initially and after aging10.30544/403 ↗
27. Influence of synthesis parameters on the particle sizes of nanostructured calciumhydroxyapatite
28. Microwave sintering improves the mechanical properties of biphasic calcium phosphates from hydroxyapatite microspheres produced from hydrothermal processing10.1007/s10853-010-4324-8 ↗
29. Synthesis and characterization of monetite and hydroxyapatite whiskers obtained by a hydrothermal method10.1016/j.ceramint.2010.08.032 ↗
30. Magnesia-doped HA/beta-TCP ceramics and evaluation of their biocompatibility10.1016/S0142-9612(03)00538-6 ↗
31. Synthesis, characterization and ab initio simulation of magnesium-substituted hydroxyapatite10.1016/j.actbio.2009.12.044 ↗
32. Antibacterial efficacy and cytotoxicity studies of copper(II) and titanium(IV) substituted hydroxyapatite nanoparticles10.1016/j.msec.2010.06.011 ↗
33. Synthesis of antimicrobial monophase silverdoped hydroxyapatite nanopowders for bone tissue engineering10.1016/j.apsusc.2010.12.113 ↗
34. Substituted hydroxyapatites with antibacterial properties
35. Magnesium incorporated hydroxyapatite nanoparticles: preparation, characterization, antibacterial and larvicidal activity10.1016/j.arabjc.2016.05.010 ↗
36. Synthesis, characterization and antimicrobial activity of copper and zinc-doped hydroxyapatite nanopowders10.1016/j.apsusc.2010.03.124 ↗
37. Antimicrobial activity of metals: mechanisms, molecular targets and applications10.1038/nrmicro3028 ↗
38. Copper substituted hydroxyapatite and fluorapatite: synthesis, characterization and antimicrobial properties10.1016/j.ceramint.2014.07.086 ↗
39. Mechanism of copper surface toxicity in vancomycin-resistant enterococci following wet or dry surface contact10.1128/AEM.00597-11 ↗
40. The pleiotropic CymR regulator of Staphylococcus aureus plays an important role in virulence and stress response10.1371/journal.ppat.1000894 ↗
41. MgO nanoparticles as antibacterial agent: preparation and activity10.1590/0104-6632.20140313s00002813 ↗
42. Quantitative evaluation of antibacterial activities of metallic oxide powders (ZnO, MgO and CaO) by conductimetric assay10.1016/S0167-7012(03)00037-X ↗
43. Impact of growth conditions on susceptibility of five microbial species to alkaline stress10.1016/j.joen.2008.02.027 ↗
44. Cu doping of calcium phosphate bioceramics: from mechanism to the control of cytotoxicity10.1016/j.actbio.2017.10.028 ↗
45. Mg-doped biphasic calcium phosphate by a solid state reaction route: characterization and evaluation of cytotoxicity10.1016/j.matchemphys.2015.05.055 ↗
46. Characterization of β-TCP, β-TCMP and BCMP produced by hydrolysis
47. Magnesium substituted hydroxyapatite whiskers: synthesis, characterization and bioactivity evaluation10.1039/C6RA24469F ↗
48. Elliott · 1994
49. Effect of Mg doping on beta-alpha phase transition in TCP bioceramics10.1016/j.actbio.2016.01.015 ↗
50. Biphasic, triphasic and multiphasic calcium orthophosphates10.1016/j.actbio.2011.09.003 ↗
51. Influence of magnesium doping on the phase transformation temperature of β−TCP ceramics examined by Rietveld refinement10.1016/j.biomaterials.2004.09.017 ↗
52. Comparative study of surface properties of Mg-substituted hydroxyapatite bioceramic microspheres10.1016/j.jeurceramsoc.2017.09.026 ↗
53. Nanocrystalline hydroxyapatite doped with magnesium and zinc: synthesis and characterization10.1016/j.msec.2006.09.036 ↗
54. Ag+, Cu2+ and Zn2+ doped hydroxyapatite/tricalcium phosphate bioceramics: influence of doping and sintering technique on mechanical properties, Process10.2298/PAC1803268R ↗
55. Microwave sintering improves the mechanical properties of biphasic calcium phosphates from hydroxyapatite microspheres produced from hydrothermal processing10.1007/s10853-010-4324-8 ↗
56. Mechanical parameters of strontium doped hydroxyapatite sintered using microwave and conventional methods10.1016/j.jmbbm.2011.07.005 ↗
57. Dense fine-grained biphasic calcium phosphate (BCP) bioceramics designed by two-step sintering10.1016/j.jeurceramsoc.2010.09.006 ↗
58. Nanocrystalline hydroxyapatite with simultaneous enhancements in hardness and toughness10.1016/j.biomaterials.2009.08.048 ↗
59. Processing of dense nanostructured HAP ceramics by sintering and hot pressing10.1016/j.ceramint.2008.07.007 ↗
60. Densification, microstructure and behavior of hydroxyapatite ceramics sintered by using spark plasma sintering10.1115/1.2931153 ↗
61. The effect of the shape and size of the pores on the mechanical properties of porous HAP-based bioceramics10.1016/j.ceramint.2010.09.014 ↗