Hydroxyapatite (HA) is a representative bone repairing biomaterial for its similar composition to human bones and teeth. However, pure HA is limited in application for some unwanted characteristic, such as it is brickle and weakness in degradation. In this study, we modified HA by doping magnesium (Mg) to the material and studied its property in vitro. Besides, we also evaluated the calvarial defect repair effect using MgHA combined with rhBMP-2 in goat model. According to our outcomes, HA composited Mg made the scaffold smooth and the pore regular. In vitro study, Mg could increase the Ca releasing, which may reflect a faster degradation property modified by Mg. And then, MgHA improved the cell viability and proliferation. Furthermore, MgHA could increase the expression of ALP, Collagen I and VEGF protein compared with pure HA (, respectively). In the vivo study, MgHA showed a better bone defect healing effect in computed tomography (CT) evaluation compared with HA (), but it was inferior to the MgHA/rhBMP-2 (). Besides, in the histological analysis, MgHA/rhBMP-2 showed the most effective bone formation outcome (), and the MgHA group was significant better than the pure HA group on osteogenesis (). Furthermore, Collagen I and VEGF mRNA expression at 12 week in MgHA/rhBMP-2 group were also significat higher than other two groups. In conclusion, Mg had effects on bone formation and angiogenesis, and MgHA/rhBMP-2 had improved the bone defect repair effect. It is worthy of being recommended to bone tissue engineering.
KimH.C.SongJ.M.KimC.J.et al., Combined effect of bisphosphonate and recombinant human bone morphogenetic protein 2 on bone healing of rat calvarial defects, Maxillofac Plast Reconstr Surg37 (2015), 16. doi:10.1186/s40902-015-0015-3.
2.
YazdiF.K.MostaghniE.MoghadamS.A.et al., A comparison of the healing capabilities of various grafting materials in critical-size defects in guinea pig calvaria, Int J Oral Maxillofac Implants28, 1370–1376. doi:10.11607/jomi.2906.
3.
LiD.DengL.YangZ.XieX.KangP. and TanZ., Antigen-free bovine cancellous bone loaded with recombinant human bone morphogenetic protein-2 for the repair of tibial bone defects in goat model, J Biomater Appl30 (2016), 1322–1333. doi:10.1177/0885328215627796.
4.
LiD.DengL.XieX.YangZ. and KangP., Evaluation of the osteogenesis and angiogenesis effects of erythropoietin and the efficacy of deproteinized bovine bone/recombinant human erythropoietin scaffold on bone defect repair, J Mater Sci Mater Med27 (2016), 101. doi:10.1007/s10856-016-5714-5.
5.
SunF.ZhouH. and LeeJ., Various preparation methods of highly porous hydroxyapatite/polymer nanoscale biocomposites for bone regeneration, Acta Biomater7 (2011), 3813–3828. doi:10.1016/j.actbio.2011.07.002.
6.
KuśnierczykK. and BasistaM., Recent advances in research on magnesium alloys and magnesium–calcium phosphate composites as biodegradable implant materials, J Biomater Appl (2016), Jul 1. doi:10.1177/0885328216657271.
7.
PalmerL.C.NewcombC.J.KaltzS.R.SpoerkeE.D. and StuppS.I., Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel, Chem Rev108(11) (2008), 4754–4783. doi:10.1021/cr8004422.
8.
Rakngarm NimkerdpholA.OtsukaY. and MutohY., Effect of dissolution/precipitation on the residual stress redistribution of plasma-sprayed hydroxyapatite coating on titanium substrate in simulated body fluid (SBF), J Mech Behav Biomed Mater36 (2014), 98–108. doi:10.1016/j.jmbbm.2014.04.007.
9.
MourinoV. and BoccacciniA.R., Bone tissue engineering therapeutics: Controlled drug delivery in three-dimensional scaffolds, J R Soc Interface7 (2010), 209–227. doi:10.1098/rsif.2009.0379.
10.
EpinetteJ.A., Long lasting outcome of hydroxyapatite-coated implants in primary knee arthroplasty: A continuous series of two hundred and seventy total knee arthroplasties at fifteen to twenty two years of clinical follow-up, Int Orthop38(2) (2014), 305–311. doi:10.1007/s00264-013-2246-1.
11.
SanliI.ArtsJ.J. and GeurtsJ., Clinical and radiologic outcomes of a fully hydroxyapatite-coated femoral revision stem: Excessive stress shielding incidence and its consequences, J Arthroplasty31(1) (2016), 209–214. doi:10.1016/j.arth.2015.08.037.
12.
JiangL.JiangL.XiongC. and SuS., Improving the degradation behavior and in vitro biological property of nano-hydroxyapatite surface- grafted with the assist of citric acid, Colloids Surf B Biointerfaces146 (2016), 228–234. doi:10.1016/j.colsurfb.2016.05.062.
13.
AltV.CheungW.H.ChowS.K.et al., Bone formation and degradation behavior of nanocrystalline hydroxyapatite with or without collagen-type 1 in osteoporotic bone defects – an experimental study in osteoporotic goats, Injury47(Suppl. 2) (2016), S58–S65. doi:10.1016/S0020-1383(16)47010-5.
14.
TavakolS.NikpourM.R.HoveiziE.et al., Investigating the effects of particle size and chemical structure on cytotoxicity and bacteriostatic potential of nano hydroxyapatite/chitosan/silica and nano hydroxyapatite/chitosan/silver; as antibacterial bone substitutes, J Nanopart Res16(10) (2014), 2622. doi:10.1007/s11051-014-2622-9.
15.
KaygiliO.KeserS.AtesT.et al., Controlling of dielectrical and optical properties of hydroxyapatite based bioceramics by Cd content, Powder Technol245 (2013), 1–6. doi:10.1016/j.powtec.2013.04.012.
16.
GuanX.XiongM.ZengF.et al., Enhancement of osteogenesis and biodegradation control by brushite coating on Mg–Nd–Zn–Zr alloy for mandibular bone repair, ACS Appl Mater Interfaces6 (2014), 21525–21533. doi:10.1021/am506543a.
17.
WangX.GuZ.JiangB.LiL. and YuX., Surface modification of strontium-doped porous bioactive ceramic scaffolds via poly(DOPA) coating and immobilizing silk fibroin for excellent angiogenic and osteogenic properties, Biomater Sci4(4) (2016), 678–688. doi:10.1039/C5BM00482A.
18.
JiangT.GuoL.NiS. and ZhaoY., Upregulation of cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on magnesium alloy surface coating with tricalcium phosphate, J Mater Sci Mater Med26 (2015), 158. doi:10.1007/s10856-015-5479-2.
19.
WitteF.KaeseV.HaferkampH.et al., In vivo corrosion of four magnesium alloys and the associated bone response, Biomaterials26 (2005), 3557–3563. doi:10.1016/j.Biomaterials2004.09.049.
20.
StaigerM.P.PietakA.M.HuadmaiJ. and DiasG., Magnesium and its alloys as orthopedic biomaterials: A review, Biomaterials27(9) (2006), 1728–1734. doi:10.1016/j.Biomaterials2005.10.003.
21.
WitteF.FischerJ.NellesenJ.et al., In vitro and in vivo corrosion measurements of magnesium alloys, Biomaterials27(7) (2006), 1013–1018. doi:10.1016/j.Biomaterials2005.07.037.
22.
ZhaoN. and ZhuD., Endothelial responses of magnesium and other alloying elements in magnesium-based stent materials, Metallomics7(1) (2015), 118–128. doi:10.1039/C4MT00244J.
23.
MaierJ.A.et al., High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro, Biochim Biophys Acta1689(1) (2004), 6–12. doi:10.1016/j.bbadis.2004.02.004.
24.
XuL.ZhangE.YinD.ZengS. and YangK., In vitro corrosion behaviour of Mg alloys in a phosphate buffered solution for bone implant application, J Mater Sci Mater Med19(3) (2008), 1017–1025. doi:10.1007/s10856-007-3219-y.
25.
LiZ.J.GuX.N.LouS.Q. and ZhengY.F., The development of binary Mg–Ca alloys for use as biodegradable materials within bone, Biomaterials29(10) (2008), 1329–1344. doi:10.1016/j.Biomaterials2007.12.021.
26.
YangY.JinG.CaoX.et al., In vitro evaluation of rhBMP-2 induced expression of VEGF in human adipose-derived stromal cells, Int J Clin Exp Med8 (2015), 222–230.
27.
SchumacherM.LodeA.HelthA. and GelinskyM., A novel strontium(II)-modified calcium phosphate bone cement stimulates human-bone-marrow-derived mesenchymal stem cell proliferation and osteogenic differentiation in vitro, Acta Biomater9(12) (2013), 9547–9557. doi:10.1016/j.actbio.2013.07.027.
28.
ZhangJ.MaX.LinD.et al., Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism, Biomaterials53 (2015), 251–264. doi:10.1016/j.Biomaterials2015.02.097.
29.
PetrieT.A.RaynorJ.E.ReyesC.D.et al., The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration, Biomaterials29(19) (2008), 2849–2857. doi:10.1016/j.Biomaterials2008.03.036.
30.
BoseS.TarafderS. and BandyopadhyayA., Effect of chemistry on osteogenesis and angiogenesis towards bone tissue engineering using 3D printed scaffolds, Ann Biomed Eng45(1) (2017), 261–272. doi:10.1007/s10439-016-1646-y.
31.
WuF.SuJ.WeiJ.et al., Injectable bioactive calcium-magnesium phosphate cement for bone regeneration, Biomed Mater3(4) (2008), 044105. doi:10.1088/1748-6041/3/4/044105.
32.
RudeR.K.GruberH.E.NortonH.J.et al., Dietary magnesium reduction to 25% of nutrient requirement disrupts bone and mineral metabolism in the rat, Bone37(2) (2005), 211–219. doi:10.1016/j.bone.2005.04.005.
33.
WeiJ.JiaJ.WuF.et al., Hierarchically microporous/macroporous scaffold of magnesium-calcium phosphate for bone tissue regeneration, Biomaterials31(6) (2010), 1260–1269. doi:10.1016/j.Biomaterials2009.11.005.
34.
WuF.WeiJ.GuoH.et al., Self-setting bioactive calcium-magnesium phosphate cement with high strength and degradability for bone regeneration, Acta Biomater4(6) (2008), 1873–1884. doi:10.1016/j.actbio.2008.06.020.
35.
MaierJ.A.BernardiniD.RayssiguierY. and MazurA., High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro, Biochim Biophys Acta1689(1) (2004), 6–12. doi:10.1016/j.bbadis.2004.02.004.
36.
BanaiS.HaggrothL.EpsteinS.E. and CasscellsW., Influence of extracellular magnesium on capillary endothelial cell proliferation and migration, Circ Res67(3) (1990), 645–650. doi:10.1161/01.RES.67.3.645.
37.
MaoZ.W.ShiH.F. and GuoR., Enhanced angiogenesis of porous collagen scaolds by incorporation of TMC/DNA complexes encoding vascular endothelial growth factor, Acta Biomater5 (2009), 2983–2994. doi:10.1016/j.actbio.2009.04.004.
38.
YuH.VandeVordP.J. and MaoL., Improved tissue-engineered bone regeneration by endothelial cell mediated vascularization, Biomaterials30 (2009), 508–517. doi:10.1016/j.Biomaterials2008.09.047.
39.
CuiW.SunG.QuY.et al., Repair of rat calvarial defects using Si-doped hydroxyapatite scaffolds loaded with a bone morphogenetic protein-2-related peptide, J Orthop Res34 (2016), 1874–1882. doi:10.1002/jor.23208.
