臺灣博碩士論文加值系統

本實驗以氫氧化鈣與磷酸為起始原料，利用共沉降法製備氫氧基磷灰石，並且利用氫氧化鍶與氫氧化鎂來進行摻雜。將製備出的漿料在1000 ℃下進行鍛燒，並且利用XPS、XRD等方式測量摻雜比例。發現，鍶的摻雜也與文獻中相同C軸方向生長，利用拉曼光譜分析與傅立葉轉換紅外光譜來確認材料內部官能基與摻雜後的變化情況，並用掃描式電子顯微鏡觀察噴塗後的表面型態與摻雜後的晶體變化，發現鍶的含量越多晶型越往針狀發展，再利用XPS來確認摻雜比例，發現確實與預估的趨勢相同。而熱噴塗方面，我們將製備的氫氧基磷灰石，利用聚乙烯醇在 17 : 1 的重量百分比下進行2天的混合球磨，將顆粒黏大後，依照需要的大小進行研磨過篩，此步驟大大提升了粉體流動性。接著調控噴塗的速率、距離與送粉孔徑，尋找最佳噴塗參數，依序噴製鈦圓板、304不銹鋼螺絲與市售牙根。最後進行MTT與ALP等生物細胞測試，發現了鍶的摻雜有助於細胞成長，但過量會具有毒性。尋找到最佳鍶濃度後，再共摻雜鎂，發現混摻5 %鍶離子和5 %鎂離子的氫氧基磷灰石噴塗至鈦圓板基材上可得最佳生物活性及生物相容性。最後，探討溼式噴塗，發現注入水後，塗層表面因為水氣衝出，造成許多裂紋與孔洞。由斷面SEM觀察得知，同樣噴塗條件下溼式噴塗的堆積較為蓬鬆，而形成的多孔性塗層影響細胞活性，在MTT與ALP上11天後，均有較顯著的成長，之後透過螢光染色顯影，可以更清楚觀察到溼式噴塗對於細胞成長的影響。

Hydroxyapatite had been to know a calcium phosphate of formula Ca10(PO4)6(OH)2 which is one of the Bisphosphonates (BPs) to consider as the most active inhibitors for bone degradation [1, 2]. In this study, we reported the fabrication of strontium and magnesium doped with hydroxyapatite by thermal spray technology coating on commercially pure Ti-disc substrates. First, HA powder was doped with 0.5, 1, 5 and 10 mole% of Sr (Sr-HA). Secondly, we co-doped 0.5, 1, 5, 10 mole% Mg (SrMg-HA) by precipitation method, heating to treat at 1000 ℃ for 4 h and then used for thermal spray coating.
Samples were confirmed to be phase pure by XRD and functional group of HA was observed by ATR-FTIR and Raman. In vitro cell–materials interactions using human embryonic palatal mesenchymal cells(HEPM) showed better cell attachment and proliferation on 1Sr-HA coatings compared to HA or other Sr-HA coatings. However, presence of 5Sr-HA coatings in the coating was better than others on the expression of alkaline phosphatase (ALP). Finally, the 5Sr5Mg-HA coatings had the best compromise for HEPM promotion and ALP activity. Our study indicated that the fabricated SrMg-HA might be a potential candidate as bioactive bone-regeneration and materials of implant coating

Contents
口試委員會審定書 I
Acknowledgement II
摘要 IIII
Abstract IV
Contents V
Figure List VIII
Table List XIII
Chapter 1 Introduction 1
Chapter 2 Literature review 3
2-1 Introduction to HA 3
2-2 Preparation of HA 5
2-2-1 Solid-state method 5
2-2-2 Precipitation method 7
2-2-3 Hydrothermal synthesis 11
2-3 The effect of dopant on HA 12
2-3-1 Strontium 12
2-3-2 Magnesium 15
2-4 Structural properties of hard tissues 17
2-4-1 Mechanical properties of bone 18
2-4-2 Structure and mechanical properties of teeth 19
2-5 Thermal spray technology for the HA-coating implant 20
Chapter 3 Experiment Procedure 28
3-1 Materials 28
3-2 Experimental 29
3-2-1 Preparation of Mg- and Sr-doped HA 29
3-2-2 Granulation and substrate processing 30
3-2-3 Thermal spray coating 30
3-3 Preosteoblast culture and test 31
3-3-1 MTT Assay-Cell Viability Analysis 31
3-3-2 ALP activity 32
3-3-3 Immunofluorescence staining 34
3-4 Characterization 34
3-4-1 Particle size 34
3-4-2 Thermal analysis 35
3-4-3 Phase identification 35
3-4-4 Surface topography 36
3-4-5 Identification of functional groups 37
3-4-6 Elemental analysis 38
3-4-7 Thermal spray processes 38
Chapter 4 Result and Discussion 39
4-1 Characteristics of HA 39
4-1-1 XRD analysis 39
4-1-2 ATR-FTIR spectra 46
4-1-3 Raman spectra 50
4-1-4 SEM images 54
4-1-5 XPS spectra 57
4-1-6 ICP-MS and adhesion strength of thermal spray coatings 62
4-2 Cell Experiments 63
4-2-1 MTT Assay 63
4-2-2 ALP activity 65
4-2-3 Immunofluorescence staining 68
Chapter 5 Conclusion 69
References 69
Figure List
Figure 2 1 The sketch of crystal structure of hydroxyapatite 5
Figure 2 2 X-ray diffraction pattern of HA specimens: (a) apatite powder before first 6
Figure 2 3 TGA/DTA curves of HA after mixing of ingredients 7
Figure 2 4 (a) TEM (Left) and HRTEM (Right) of HA; (b) TEM (Left) and HRTEM (Right) of 0.3% Sr-HA; (c) TEM (Left) and HRTEM (Right) of 1.5% Sr-HA; (d) TEM (Left) and HRTEM (Right) of 15% Sr-HA. 9
Figure 2 5 Morphology of HA starting powders: high (a), medium (b) and low (c) crystallinity degree. 10
Figure 2 6 The morphologies of the synthetic Sr-HA porous microspheres: (A, B) Sr1-HA, (C, D) Sr3-HA and (E, F) Sr5-HA. 12
Figure 2 7 Proliferation of MG-63 cells cultured on PEEK, 25 vol% Sr-HA/PEEK and 25 vol% HA/PEEK composites from 3 to 14 days. 13
Figure 2 8 Alkaline phosphatase activity of MG-63 cells on PEEK, 25 vol% Sr-HA/PEEK and 25 vol% HA/PEEK composites from 3 to 14 days. 14
Figure 2 9 Osteoclast proliferation and differentiation (TRAP%, 14 days) in co-cultures with osteoblasts on the different materials. 14
Figure 2 10 A. Raman spectra of pure and Mg2+-substituted HA samples in the spectral range of 1,100–300 cm-1. Spectrum (a) Ca10 (PO4)6(OH)2; spectrum (b) Ca9.9Mg0.1(PO4)6(OH)2; spectrum (c) Ca9.5Mg0.5(PO4)6(OH)2; spectrum (d) Ca9Mg1(PO4)6(OH)2. Inserted reference materials: spectrum (1) α-Ca3(PO4)2, spectrum (2) β-Ca3(PO4)2. B. Spectral deconvolutions in the spectral range of 16
Figure 2 11 Hierarchical levels of structural organization in a human long bone[61]. 18
Figure 2 12 A representative load-deflection curve for human compact bone[61]. 19
Figure 2 13 Schematic diagram of a tooth. 19
Figure 2 14 Residual stress through the thickness of air plasma 21
Figure 2 15 (A) Conventional hydroxyapatite coating implant. (B) Silver-containing 22
Figure 2 16 Regions of interests (ROI 1-5) for the measurements of the bone-to-implant contact (BIC). ROI 1 and 4 in the gap of the middle part of the implant, ROI 2 and 3 in the threaded apical part and ROI 5 at the tip of 25
Figure 2 17 Showing the histological outcome after 2 days of healing for all three groups. 26
Figure 2 18 Showing the histological outcome after 7 days of healing for all three groups. 27
Figure 2 19 Showing the histological outcome after 6 months of healing for all three groups. 27
Figure 3 1 Different thickness of HA coating 31
Figure 3 2 The particle size of HA was determine with a particle size and zeta potential analyzer. 35
Figure 3 3 Thermogravimetry / Differential Thermal Analysis Thermoanalyzer. 35
Figure 3 4 X-Ray Diffraction. 36
Figure 3 5 FESEM 37
Figure 3 6 Fourier transform infrared spectroscopy 37
Figure 3 7 X-Ray Photoelectron Spectroscopy 38
Figure 3 8 Thermal spray coating applications 39
Figure 4 1 XRD patterns of (a) HA 0 ℃ (b) HA 200 ℃ (c) HA 400 ℃ (d) HA 600 ℃ (e) HA 800 ℃ (f) HA 1000 ℃ (pH = 10~11). 40
Figure 4 2 XRD patterns of (a) 923-ICSD α-TCP (b) 6191-ICSD β-TCP (c) HA 0 ℃ (d) HA 200 ℃ (e) HA 400 ℃ (f) HA 600 ℃ (g) HA 800 ℃ (h) HA 1000 ℃ (pH=5~6). 40
Figure 4 3 XRD patterns of (a) JCPDS 09-0432 (b) Metco. (c) HA (d) 0.5Sr-HA (e) 1Sr-HA (f) 5Sr-HA (g) 10Sr-HA (h) 5Sr0.5Mg-HA (i) 5Sr1Mg-HA (j) 5Sr5Mg-HA (k) 5Sr10Mg-HA. 42
Figure 4 4 XRD patterns of HA coating on titanium discs by thermal spray technologies (a) D1 (b) D2 (c) D3 (d) W1 (e) W2 (f) W3. 45
Figure 4 5 ATR-FTIR spectra for (a) HA (b) 0.5Sr-HA (c) 1Sr-HA (d) 5Sr-HA (e) 10Sr-HA. 47
Figure 4 6 ATR-FTIR spectra for (a) 5Sr0.5Mg-HA (b) 5Sr1Mg-HA (c) 5Sr5Mg-HA (d) 5Sr10Mg-HA. 48
Figure 4 7 Raman spectra for (a) HA (b) 0.5Sr-HA (c) 1Sr-HA (d) 5Sr-HA (e) 10Sr-HA. 51
Figure 4 8 Raman spectra for (a) HA (b) 0.5Sr-HA (c) 1Sr-HA (d) 5Sr-HA (e) 10Sr-HA (920–990 cm-1 region). 52
Figure 4 9 Raman spectra for (a) 5Sr0.5Mg-HA (b) 5Sr1Mg-HA (c) 5Sr5Mg-HA (d) 5Sr10Mg-HA. 53
Figure 4 10 Raman spectra for (a) 5Sr0.5Mg-HA (b) 5Sr1Mg-HA (c) 5Sr5Mg-HA (d) 5Sr10Mg-HA (920–990 cm-1 region). 54
Figure 4 11 SEM images of the obtained (a) pure HA (b) HA+PVA 55
Figure 4 12 SEM images of the synthesized samples: (a) 0.5Sr-HA (b) 1Sr-HA (c) 5Sr-HA (d) 10Sr-HA (e) 5Sr0.5Mg-HA (f) 5Sr1Mg-HA (g) 5Sr5Mg-HA (h) 5Sr10Mg-HA. 56
Figure 4 13 Surfaces microstructure of HA (a) dry coating, (b) wet coating, and cross- sectional microstructure of HA (c) dry, (d) wet coating. 57
Figure 4 14 The XPS spectra of (a) Ca2p in HA, Sr-HA and SrMg-HA. 59
Figure 4 15 The XPS spectra of (a) O1s in HA, Sr-HA and SrMg-HA. 60
Figure 4 16 Adhesive strength of the coatings to the substrate 62
Figure 4 17 Ca, P, Sr and Mg concentration in water during the release from coatings of 5Sr5Mg-HA (N=3). 63
Figure 4 18 HEPM cell proliferation on Sr-HA and HA coatings (n=4, *p < 0.05). 64
Figure 4 19 HEPM cell proliferation on SrMg-HA and HA coatings (n=4, *p < 0.05). 65
Figure 4 20 HEPM cell proliferation on dry spray coating and wet spray coating (n=4, *p < 0.05). 65
Figure 4 21 Alkaline phosphatase activity of HEPM cells on HA and Sr-HA coatings from 3 to 11 days. Significant difference in ALP activity between HA, and Sr-HA coatings at each culture period was observed (n=4, *p < 0.05). 66
Figure 4 23 Alkaline phosphatase activity of HEPM cells on HA and SrMg-HA coatings from 3 to 11 days. Significant difference in ALP activity between HA and SrMg-HA coatings at each culture period was observed (n=4, p* < 0.05). 67
Figure 4 24 Alkaline phosphatase activity of HEPM cells on dry spray coating and wet spray coating from 3 to 11 days. Significant difference in ALP activity between dry spray coating and wet spray coating at each culture period was observed (n=4, *p< 0.05). 67
Figure 4 25 Immunofluorescence staining in HEPM cells on dry spray coating and wet spray coating from 1 to 7 days. 68
Table List
Table 2 1 Some calcium phosphate compound 4
Table 2 2 Characteristics for the all samples. 15
Table 2 3 Data obtained by XRD analysis. 16
Table 2 4 Patient data. 17
Table 2 5 Percentages of graft integration. 17
Table 2 6 Demographic Descriptions of the Patient Cohort, the Indication for THA, and the Total Silver Mass of the Prosthesis. 23
Table 2 7 Laboratory Data at Preoperation and Postoperation. 23
Table 2 8 Showing the data set for all the three groups (BP, M, and P) at the three time points (2 and 7 days, and 6 months) 26
Table 3 1 A list of properties of initial materials 28
Table 3 2 Substrate and Cell Culture Consumables 29
Table 3 3 The HA-coating parameters. 31
Table 4 1 the diffraction peak intensity (211) of HA 41
Table 4 2 Lattice parameters of HA, Sr-HA and SrMg-HA. 43
Table 4 3 Crystal size and peak intensity of HA, Sr-HA and SrMg-HA reflected by XRD pattern 44
Table 4 4 The diffraction peak comparison of dry coating and wet coating 45
Table 4 5 ATR-FTIR bands and their assignments for HA, Sr-HA and SrMg-HA. 49
Table 4 6 Atomic concentration table for HA, Sr-HA and SrMg-HA (atomic %) 61

1.Boanini E., Torricelli P., Gazzano M., Della Bella E., Fini M., and Bigi A., Combined effect of strontium and zoledronate on hydroxyapatite structure and bone cell responses. Biomaterials, 2014. 35(21): p. 5619-5626.
2.Aina V., Bergandi L., Lusvardi G., Malavasi G., Imrie F.E., Gibson I.R., Cerrato G., and Ghigo D., Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells. Mater Sci Eng C Mater Biol Appl, 2013. 33(3): p. 1132-1142.
3.Robert W.B., Ann C., and Ralph H., Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures. Clin Orthop Relat Res, 1989. 187(240): p. 53–62.
4.Hoogendoorn HA., Renooij W., Visser W., and Wittebol P., Long-term study of large ceramic implants (porous hydroxyapatite) in dog femora. Clin Orthop Relat Res, 1984. 187: p. 281–288.
5.Evis Z. and Webster T.J., Nanosize hydroxyapatite: doping with various ions. Advances in Applied Ceramics, 2013. 110(5): p. 311-321.
6.Bruice T.C., BlaskoÄ A., and Petyak A.M.E., Structure and Chemistry of the Apatites and Other Calcium Orthophosphates. J. Am. Chem. Soc.,, 1996. 118(12): p. 3071.
7.Curran D.J., Fleming T.J., Towler M.R., and Hampshire S., Mechanical parameters of strontium doped hydroxyapatite sintered using microwave and conventional methods. J Mech Behav Biomed Mater, 2011. 4(8): p. 2063-2073.
8.Takahashi N., Sasaki T., Tsouderos Y., and Suda T., S 12911-2 Inhibits Osteoclastic Bone Resorption In Vitro. Journal of Bone and Mineral Research, 2003. 18(6): p. 1082-1087.
9.Canalis E., Hott M., Deloffre P., Y. Tsouderos, and Marie P.J., The Divalent Strontium Salt S12911 Enhances Bone Cell Replication and Bone Formation In Vitro. Bone, 1996. 18(6): p. 517-523.
10.Onder S., Calikoglu-Koyuncu A.C., Kazmanli K., Urgen M., Torun Kose G., and Kok F.N., Behavior of mammalian cells on magnesium substituted bare and hydroxyapatite deposited (Ti,Mg)N coatings. N Biotechnol, 2015. 32(6): p. 747-755.
11.Stipniece L., Salma-Ancane K., Borodajenko N., Sokolova M., Jakovlevs D., and Berzina-Cimdina L., Characterization of Mg-substituted hydroxyapatite synthesized by wet chemical method. Ceramics International, 2014. 40(2): p. 3261-3267.
12.Chen W., Liu Y., Courtney H.S., Bettenga M., Agrawal C.M., Bumgardner J.D., and Ong J.L., In vitro anti-bacterial and biological properties of magnetron co-sputtered silver-containing hydroxyapatite coating. Biomaterials, 2006. 27(32): p. 5512-5517.
13.Li Z.Y., Lam W.M., Yang C., Xu B., Ni G.X., Abbah S.A., Cheung K.M., Luk K.D., and Lu W.W., Chemical composition, crystal size and lattice structural changes after incorporation of strontium into biomimetic apatite. Biomaterials, 2007. 28(7): p. 1452-1460.
14.Gross K.A. and Berndt C.C., Thermal processing of hydroxyapatite for coating production. J Biomed Mater Res, 1997. 39(4): p. 580-587.
15.Lang S.B., Tofail S.A., Kholkin A.L., Wojtas M., Gregor M., Gandhi A.A., Wang Y., Bauer S., Krause M., and Plecenik A., Ferroelectric polarization in nanocrystalline hydroxyapatite thin films on silicon. Sci Rep, 2013. 3: p. 2215.
16.Raina D.B., Isaksson H., Hettwer W., Kumar A., Lidgren L., and Tagil M., A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone. Sci Rep, 2016. 6: p. 26033.
17.Sun D., Chen Y., Tran R.T., Xu S., Xie D., Jia C., Wang Y., Guo Y., Zhang Z., Guo J., Yang J., Jin D., and Bai X., Citric acid-based hydroxyapatite composite scaffolds enhance calvarial regeneration. Sci Rep, 2014. 4: p. 6912.
18.Zhang Y., Deng X., Jiang D., Luo X., Tang K., Zhao Z., Zhong W., Lei T., and Quan Z., Long-term results of anterior cervical corpectomy and fusion with nano-hydroxyapatite/polyamide 66 strut for cervical spondylotic myelopathy. Sci Rep, 2016. 6: p. 26751.
19.Zhang Y., Liu W., Banks C.E., Liu F., Li M., Xia F., and Yang X., A fluorescence-quenching platform based on biomineralized hydroxyapatite from natural seashell and applied to cancer cell detection. Sci Rep, 2014. 4: p. 7556.
20.Zhao M., Li H., Liu X., Wei J., Ji J., Yang S., Hu Z., and Wei S., Response of Human Osteoblast to n-HA/PEEK--Quantitative Proteomic Study of Bio-effects of Nano-Hydroxyapatite Composite. Sci Rep, 2016. 6: p. 22832.
21.Laurencin C.T., Khan Y., and Veronick J., Bone Graft Substitutes: Past, Present, and Future. Bone Graft Substitutes and Bone Regenerative Engineering: p. 1-9.
22.Lan J.M., Tomin E., and Bostrom M.P.G., Biosynthetic Bone Grafting. Clin. Orthop Relat. R., 1999. 367: p. 107-117.
23.LeGeros R.Z., Properties of Osteoconductive Biomaterials: Calcium Phosphates. Clinical Orthopaedics and Related Research, 2002. 395: p. 81-98.
24.Bucholz R.W., Carlton A., and Holmes R., Interporous Hydroxyapatite as a Bone Graft Substitute in Tibia1 Plateau Fractures. Clin Orthop Relat Res, 1998. 240: p. 53-62.
25.Kumta P.N., Sfeir C., Lee D.H., Olton D., and Choi D., Nanostructured calcium phosphates for biomedical applications: novel synthesis and characterization. Acta Biomater, 2005. 1(1): p. 65-83.
26.Habibovic P. and de Groot K., Osteoinductive biomaterials--properties and relevance in bone repair. J Tissue Eng Regen Med, 2007. 1(1): p. 25-32.
27.Oryan A., Alidadi S., Moshiri A., and Maffulli N., Bone regenerative medicine: classic options, novel strategies, and future directions. journal of orthopaedic surgery and research, 2014. 9: p. 18.
28.West A.R., Wiley, and Sons, Solid State Chemistry and its Applications. 2005.
29.Pramanik S., Agarwal A.K., Rai K.N., and Garg A., Development of high strength hydroxyapatite by solid-state-sintering process. Ceramics International, 2007. 33(3): p. 419-426.
30.Adler A.D., Longo F.R., Kampas F., and Kim J., On the preparation of metalloporphyrins. Journal of Inorganic and Nuclear Chemistry, 1970. 32(7): p. 2443.
31.Landi E., Tampieri A., and G. Celotti S.S., Densification behaviour and mechanisms of synthetic hydroxyapatites. Journal of the European Ceramic Society, 2000. 20(14-15): p. 2377-2387.
32.Lin K., Liu P., Wei L., Zou Z., Zhang W., Qian Y., Shen Y., and Chang J., Strontium substituted hydroxyapatite porous microspheres: Surfactant-free hydrothermal synthesis, enhanced biological response and sustained drug release. Chemical Engineering Journal, 2013. 222: p. 49-59.
33.Elliott J.C., Structure and chemistry of the apatites and other calcium orthophosphates. Elsevier Science Inc., 1994. 118(12): p. 3071-3072.
34.Zeglinski J., Nolan M., Bredol M., Schatte A., and Tofail S.A., Unravelling the specific site preference in doping of calcium hydroxyapatite with strontium from ab initio investigations and Rietveld analyses. Phys Chem Chem Phys, 2012. 14(10): p. 3435-3443.
35.Chung C.J. and Long H.Y., Systematic strontium substitution in hydroxyapatite coatings on titanium via micro-arc treatment and their osteoblast/osteoclast responses. Acta Biomater, 2011. 7(11): p. 4081-7.
36.Boyd A.R., Rutledge L., Randolph L.D., and Meenan B.J., Strontium-substituted hydroxyapatite coatings deposited via a co-deposition sputter technique. Mater Sci Eng C Mater Biol Appl, 2015. 46: p. 290-300.
37.Gopi D., Ramya S., Rajeswari D., Karthikeyan P., and Kavitha L., Strontium, cerium co-substituted hydroxyapatite nanoparticles: Synthesis, characterization, antibacterial activity towards prokaryotic strains and in vitro studies. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014. 451: p. 172-180.
38.Li Y., Feng G., Gao Y., Luo E., Liu X., and Hu J., Strontium ranelate treatment enhances hydroxyapatite-coated titanium screws fixation in osteoporotic rats. J Orthop Res, 2010. 28(5): p. 578-82.
39.Schumacher M. and Gelinsky M., Strontium modified calcium phosphate cements – approaches towards targeted stimulation of bone turnover. J. Mater. Chem. B, 2015. 3(23): p. 4626-4640.
40.Wang X., Wang Y., Li L., Gu Z., Xie H., and Yu X., Stimulations of strontium-doped calcium polyphosphate for bone tissue engineering to protein secretion and mRNA expression of the angiogenic growth factors from endothelial cells in vitro. Ceramics International, 2014. 40(5): p. 6999-7005.
41.Kavitha M., Subramanian R., Narayanan R., and Udhayabanu V., Solution combustion synthesis and characterization of strontium substituted hydroxyapatite nanocrystals. Powder Technology, 2014. 253: p. 129-137.
42.Xue W., Hosick H.L., Bandyopadhyay A., Bose S., Ding C., Luk K.D.K., Cheung K.M.C., and Lu W.W., Preparation and cell–materials interactions of plasma sprayed strontium-containing hydroxyapatite coating. Surface and Coatings Technology, 2007. 201(8): p. 4685-4693.
43.Vahabzadeh S., Roy M., Bandyopadhyay A., and Bose S., Phase stability and biological property evaluation of plasma sprayed hydroxyapatite coatings for orthopedic and dental applications. Acta Biomater, 2015. 17: p. 47-55.
44.Ni G.X., Lu W.W., Xu B., Chiu K.Y., Yang C., Li Z.Y., Lam W.M., and Luk K.D., Interfacial behaviour of strontium-containing hydroxyapatite cement with cancellous and cortical bone. Biomaterials, 2006. 27(29): p. 5127-33.
45.Tavares D.d.S., Resende C.X., Quitan M.P., Castro L.d.O., Granjeiro J.M., and Soares G.d.A., Incorporation of strontium up to 5 Mol. (%) to hydroxyapatite did not affect its cytocompatibility. Materials Research, 2011. 14(4): p. 456-460.
46.Xu J., Yang Y., Wan R., Shen Y., and Zhang W., Hydrothermal preparation and characterization of ultralong strontium-substituted hydroxyapatite whiskers using acetamide as homogeneous precipitation reagent. ScientificWorldJournal, 2014. 2014: p. 863137.
47.Verberckmoes S.C., Behets G.J., Oste L., Bervoets A.R., Lamberts L.V., Drakopoulos M., Somogyi A., Cool P., Dorrine W., De Broe M.E., and D''Haese P.C., Effects of strontium on the physicochemical characteristics of hydroxyapatite. Calcif Tissue Int, 2004. 75(5): p. 405-415.
48.Brook I., Freeman C., Grubb S., Cummins N., Curran D., Reidy C., Hampshire S., and Towler M., Biological evaluation of nano-hydroxyapatite-zirconia (HA-ZrO2) composites and strontium-hydroxyapatite (Sr-HA) for load-bearing applications. J Biomater Appl, 2012. 27(3): p. 291-298.
49.Wong K.L., Wong C.T., Liu W.C., Pan H.B., Fong M.K., Lam W.M., Cheung W.L., Tang W.M., Chiu K.Y., Luk K.D., and Lu W.W., Mechanical properties and in vitro response of strontium-containing hydroxyapatite/polyetheretherketone composites. Biomaterials, 2009. 30(23-24): p. 3810-3817.
50.Su Y., Li D., Su Y., Lu C., Niu L., Lian J., and Li G., Improvement of the Biodegradation Property and Biomineralization Ability of Magnesium–Hydroxyapatite Composites with Dicalcium Phosphate Dihydrate and Hydroxyapatite Coatings. ACS Biomaterials Science & Engineering, 2016. 2(5): p. 818-828.
51.Huang B., Yuan Y., Li T., Ding S., Zhang W., Gu Y., and Liu C., Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface. Sci Rep, 2016. 6: p. 24323.
52.Kheradmandfard M. and Fathi M.H., Preparation and characterization of Mg-doped fluorapatite nanopowders by sol–gel method. Journal of Alloys and Compounds, 2010. 504(1): p. 141-145.
53.Mroz W., Budner B., Syroka R., Niedzielski K., Golanski G., Slosarczyk A., Schwarze D., and Douglas T.E., In vivo implantation of porous titanium alloy implants coated with magnesium-doped octacalcium phosphate and hydroxyapatite thin films using pulsed laser depostion. J Biomed Mater Res B Appl Biomater, 2015. 103(1): p. 151-158.
54.Li X., Li Y., Liao Y., Li J., Zhang L., and Hu J., The effect of magnesium-incorporated hydroxyapatite coating on titanium implant fixation in ovariectomized rats. Int J Oral Maxillofac Implants, 2014. 29(1): p. 196-202.
55.Aina V., Lusvardi G., Annaz B., Gibson I.R., Imrie F.E., Malavasi G., Menabue L., Cerrato G., and Martra G., Magnesium- and strontium-co-substituted hydroxyapatite: the effects of doped-ions on the structure and chemico-physical properties. J Mater Sci Mater Med, 2012. 23(12): p. 2867-2879.
56.O''Donnell M.D., Fredholm Y., de Rouffignac A., and Hill R.G., Structural analysis of a series of strontium-substituted apatites. Acta Biomater, 2008. 4(5): p. 1455-1464.
57.Aminzadeh A., Fluorescence bands in the FT-Raman spectra of some calcium minerals. Spectrochimica Acta Part A, 1997. 53(5): p. 693-697.
58.Dallari D., Savarino L., Albisinni U., Fornasari P., Ferruzzi A., Baldini N., and Giannini S., A prospective, randomised, controlled trial using a Mg-hydroxyapatite - demineralized bone matrix nanocomposite in tibial osteotomy. Biomaterials, 2012. 33(1): p. 72-79.
59.Fung Y.C., Biomechanics. Mechanical Properties of Living Tissues. Springer-Verlag Inc., New York, 1993: p. 500.
60.J. D. Currey e.b.A.K.a.S.T.M., Handbook of Composites. Elsevier Science Publishers B. V., 1983. 4: p. 501.
61.Park J.B., Biomaterials Science and Engineering. Plenum Press, New York, 1987.
62.Suchanek W. and Yoshimura M., Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants. Journal of Materials Research, 2011. 13(01): p. 94-117.
63.Barralet J., Knowles J.C., and Bonifield S.B.W., Thermal decomposition of synthesised carbonate hydroxyapatite. Journal of maTERIALS SCIENCE IN MEDICINE, 2002. 13: p. 529-533.
64.Weng J., Liu X., Zhang X., and JI X., Thermal decomposition of hydroxyapatite structure induced by titanium and its dioxide. JOURNAL OF MATERIALS SCIENCE LETTERS, 1994. 13: p. 159-161.
65.Hobbs M.K. and Reiter H., RESIDUAL STRESSES IN Zr02-8%Y203 PLASMA-SPRAYED THERMAL BARRIER COATINGS. Surface and Coatings Technology, 1988. 34: p. 33-34.
66.Brown S.R., Turner I.G., and Reiter H., Residual stress measurement in thermal sprayed hydroxyapatite coatings. JOURNAL OF MATERIALS SCIENCE: MATERIALS IN MEDICINE, 1994. 5: p. 756-759.
67.Eto S., Kawano S., Someya S., Miyamoto H., Sonohata M., and Mawatari M., First Clinical Experience With Thermal-Sprayed Silver Oxide-Containing Hydroxyapatite Coating Implant. J Arthroplasty, 2016. 31(7): p. 1498-503.
68.Sengstock C., Diendorf J., Epple M., Schildhauer T.A., and Koller M., Effect of silver nanoparticles on human mesenchymal stem cell differentiation. Beilstein J Nanotechnol, 2014. 5: p. 2058-2069.
69.Hardes J., von Eiff C., Streitbuerger A., Balke M., Budny T., Henrichs M.P., Hauschild G., and Ahrens H., Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma. J Surg Oncol, 2010. 101(5): p. 389-395.
70.Hussmann B., Johann I., Kauther M.D., Landgraeber S., Jager M., and Lendemans S., Measurement of the silver ion concentration in wound fluids after implantation of silver-coated megaprostheses: correlation with the clinical outcome. Biomed Res Int, 2013. 2013: p. 763096.
71.Eto S., Miyamoto H., Shobuike T., Noda I., Akiyama T., Tsukamoto M., Ueno M., Someya S., Kawano S., Sonohata M., and Mawatari M., Silver oxide-containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur. J Orthop Res, 2015. 33(9): p. 1391-1397.
72.Schmitt C.M., Koepple M., Moest T., Neumann K., Weisel T., and Schlegel K.A., In vivo evaluation of biofunctionalized implant surfaces with a synthetic peptide (P-15) and its impact on osseointegration. A preclinical animal study. Clin Oral Implants Res, 2016. 27(11): p. 1339-1348.
73.TE L., R Y., S S.M., and R. M., The Putative Collagen Binding Peptide Hastens Periodontal Ligament Cell Attachment to Bone Replacement Graft Materials. J Periodontol, 2001. 72(8): p. 990-997.
74.JJ Q. and RS B., Enhanced cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen. J Biomed Mater Res., 1996. 31(4): p. 545-554.
75.R. S. Bhatnagar, Qian J.J., Wedrychowska A., Dixon E., Smith N., and Beirne O.R., Biomimetic Habitats for Cells: Ordered Matrix Deposition and Differentiation in Gingival Fibroblasts Cultured on Hydroxyapatite Coated with a Collagen Analogue. Cells and Materials, 1999. 9(2): p. 93-104.
76.Nguyen H., Qian J.J., Bhatnagar R.S., and Li S., Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels. Biochemical and Biophysical Research Communications, 2003. 311(1): p. 179-186.
77.Fan Y., Sun Z., and Moradian-Oldak J., Controlled remineralization of enamel in the presence of amelogenin and fluoride. Biomaterials, 2009. 30(4): p. 478-483.
78.de Lima I.R., Alves G.G., Soriano C.A., Campaneli A.P., Gasparoto T.H., Ramos E.S., Jr., de Sena L.A., Rossi A.M., and Granjeiro J.M., Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility. J Biomed Mater Res A, 2011. 98(3): p. 351-358.
79.Kaygili O. and Keser S., Zr/Mg, Zr/Sr and Zr/Zn co-doped hydroxyapatites: Synthesis and characterization. Ceramics International, 2016. 42(7): p. 9270-9273.
80.Geng Z., Cui Z., Li Z., Zhu S., Liang Y., Lu W.W., and Yang X., Synthesis, characterization and the formation mechanism of magnesium- and strontium-substituted hydroxyapatite. J. Mater. Chem. B, 2015. 3(18): p. 3738-3746.
81.Roy M., Bandyopadhyay A., and Bose S., Induction plasma sprayed Sr and Mg doped nano hydroxyapatite coatings on Ti for bone implant. J Biomed Mater Res B Appl Biomater, 2011. 99(2): p. 258-65.
82.Silva C.C. and Sombra A.S.B., Raman spectroscopy measurements of hydroxyapatite obtained by mechanical alloying. Journal of Physics and Chemistry of Solids, 2004. 65(5): p. 1031-1033.
83.Parker J.M.., Seddon A.B., fibres. I.-t.o., M C., and JM P., High-performance glasses. London : Blackie. 1992: p. 252-286.
84.Kannan S., Lemos A.F., Rocha J.H.G., and Ferreira J.M.F., Characterization and Mechanical Performance of the Mg-Stabilized beta-Ca3(PO4)2 Prepared from Mg-Substituted Ca-Deficient Apatite. Journal of the American Ceramic Society, 2006. 0(0): p. 2757-2761.
85.International Designation, Standard Test Method for Adhesion or Cohesion Strength of Thermal Spray Coatings, C633 − 13.
86.Geng Z., Wang R., Li Z., Cui Z., Zhu S., Liang Y., Liu Y., Huijing B., Li X., Huo Q., Liu Z., and Yang X., Synthesis, characterization and biological evaluation of strontium/magnesium-co-substituted hydroxyapatite. J Biomater Appl, 2016. 31(1): p. 140-151.
87.Bodhak S., Bose S., and Bandyopadhyay A., Bone cell–material interactions on metal-ion doped polarized hydroxyapatite. Materials Science and Engineering: C, 2011. 31(4): p. 755-761.