Carbonated hydroxyapatite starting from calcite and different orthophosphates under moderate hydrothermal conditions: Synthesis and surface reactivity in simulated body fluid

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Carbonated hydroxyapatite starting from calcite and

different orthophosphates under moderate hydrothermal

conditions: Synthesis and surface reactivity in simulated

body fluid

Doan Pham Minh, Ange Nzihou, Patrick Sharrock

To cite this version:

Doan Pham Minh, Ange Nzihou, Patrick Sharrock. Carbonated hydroxyapatite starting from

cal-cite and different orthophosphates under moderate hydrothermal conditions: Synthesis and surface

reactivity in simulated body fluid. Materials Research Bulletin, Elsevier, 2014, 60, p. 292-299.

�10.1016/j.materresbull.2014.08.052�. �hal-01611606�

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Carbonated

hydroxyapatite

starting

from

calcite

and

different

orthophosphates

under

moderate

hydrothermal

conditions:

Synthesis

and

surface

reactivity

in

simulated

body

ﬂuid

Doan

Pham

Minh

*

,

Ange

Nzihou,

Patrick

Sharrock

UniversitédeToulouse,MinesAlbi,CNRSUMR5302,CentreRAPSODEE,CampusJarlard,F-81013Albicedex09,France

Keywords: Structuralmaterials Chemicalsynthesis Infraredspectroscopy Surfaceproperties ABSTRACT

Theone-stepsynthesisofcarbonatedhydroxyapatite(CAP)usingcalciteanddifferentorthophosphates was investigatedina closedbatchreactor. Onlyorthophosphoric acidcould leadto thecomplete decompositionofcalciteparticles,whenthereactiontemperaturewassetat80!_C._On_the_other_hand,_the

reactiontimeandthedilutionof theinitialcalcitesuspensionhadnosignificantinfluenceonthe formationofthesolidproducts.CAPwasformedasthemaincrystallinecalciumphosphatewiththe carbonatecontentintherangeof4.2–4.6wt.%.ThethermaldecarbonationofthesynthesizedCAPstarted at750!_C_but_it_was_only_significant_at₁₀₀₀!_C_under_air_atmosphere._This_thermal_{decarbonation}_was

totalat1200!_C_or_above._All_CAP_samples _and_products_following_thermal_treatments_were_found

bioactiveinthetestusingsimulatedbodyﬂuid(SBF)solution.

1. Introduction

Theinorganicmineralphaseofhumanteethandboneismainly composed of calcium hydroxyapatite (Ca-HA, Ca10(PO4)6(OH)2),

withdifferentsubstitutionssuchassodium,magnesium,chloride, ﬂuoride, carbonate,etc. [1–3].This explainsthe interestin the developmentofCa-HAandsubstitutedCa-HAinthebiomaterials ﬁeld,duetotheirbiocompatibilityandbioactivity[4,5]. Substitut-ed Ca-HA is formedwhen calcium,phosphate,and/or hydroxyl groups of Ca-HA structure are replaced by other metals and functionalgroups.Thus,bonemineralhasusuallythemolarratio ofcalciumtophosphatevaryingintherangeof1.37–1.87compared withthatof1.67forstoichiometricCa-HA[3].Ingeneral,carbonate isfoundtobethemostabundantsubstitutionanditscontentin bonemineralvariesintherangeof3–8wt.%[6].Carbonategroups caninsertintheapatiticstructurebyreplacingphosphateand/or hydroxyl groups to form carbonated hydroxyapatite (CAP). Conventionally,CAPisA-typeCAPwhencarbonategroupsreplace phosphate groups;B-type CAP when carbonate groups replace hydroxyl groups; and A-B-type CAP when carbonate groups replacesimultaneouslyphosphateandhydroxylgroups.

ThesynthesisofCAPcallsusuallyfortheclassicalwetanddry methods.Inthewetprocess,solublecalciumandphosphatesare

precipitatedinanaqueoussolutioninthepresenceofcarbonate anions[7,8].ThisprocessleadsgenerallytotheformationofB-type CAP [7] but A-B-type CAPmay be also formed[9]. In the dry process,A-typeCAPcouldbegenerated byheatingpureCa-HA underCO2ﬂuxathightemperatureinordertoreplacehydroxyl

groupsbycarbonategroups[10].CAPcouldbealsoobtainedbythe commonmechano-chemicalprocessasdemonstratedby Sucha-neket al.[11],whereinanaqueous suspensionof Ca(OH)2 and

CaCO3(orNa2CO3)and (NH4)2HPO4 aretreatedina

laboratory-scalemill.Butthislastwayrequiresseverereactionconditions. We recently developed a new one-step synthesis process of Ca-HAfromCaCO3andorthophosphoricacid(H3PO4)aseconomical

starting materials at moderate synthesis conditions [12]. The advantageofthisprocesscomparedto classicalCa-HA synthesis pathways remainsin the factthat pure Ca-HA canbeobtained withoutanyfurtherpuriﬁcationstep,thankstotheabsenceofall counterionsinthereactionmedium[12].Amodiﬁcationofthis processwasthendevelopedfortheone-stepsynthesisofCAPunder moderatehydrothermalconditions[13].CAPcontaining4.2wt.%of carbonatecouldbeobtainedfromthereactionofCaCO3andH3PO4in

aclosebatchreactorunderCO2pressure.CaCO3waschosenbecause

itisthesourceofbothcalciumcationsandcarbonateanionsforthe formationofCAP,andalsobecauseithasconsiderableindustrial importanceandabundantdiversityasabiomineral[14].Inthiswork, we ﬁrstlycompared thereaction of calcite with different alkali orthophosphates and orthophosphoric acid in orderto selectthe best orthophosphate.Then,weinvestigatedtheinﬂuenceofdifferent

* Correspondingauthor.Tel.:+33563493258;fax:+33563493043. E-mailaddress:doan.phamminh@mines-albi.fr(D.PhamMinh).

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parameters includingthecontentofwaterintheinitialsuspensionof CaCO3, the reaction temperature and the reaction time, on the

contentofcarbonateinserted intheﬁnalsolidCAP. Theinvitro biomineralizationactivityofthesolidCAPproductcontainingthe highestcarbonatecontentwasalsoinvestigatedbeforeandafter thermaltreatmentatdifferenttemperatures.

2. Materialsandmethods

Orthophosphoricacid(H3PO4,85wt.%inwater)waspurchased

from Merck. Calcitepowder (CaCO3, d50of 23.6

m

m), and alkali

orthophosphates(NaH2PO4,KH2PO4,NH4H2PO4)ofanalyticalpurity

from Fisher Scientiﬁc were used as received without further puriﬁcation.The reaction of CaCO3 with these orthophosphates

was carried out in a 250mL stainless steel close batchreactor (TopIndustry,France) whichwasequippedwithanelectricalheating jacketandamagneticstirrer.Whenorthophosphoricacidwasused, 10gof calcite powderand45–135gof water were fedintothe reactor. Thereactorwasclosedandthen6.92gH3PO4(85wt.%)wasquickly

injectedintothereactorviaasyringe.Whenalkaliorthophosphates wereused,10gofwaterwassetintothereactor.Thislastonewas closedand135gofanaqueoussolutioncontaining60mmolofan alkaliorthophosphatewasquicklyinjectedintothereactor.Inall

case,themolarratioofcalciumtophosphorusintheinitialreaction mixturewas1.67.Thereactionmixturewaskeptat60or80!_C_under

stirringof800rpmfor48–168hofreaction.Theconditionsforthe synthesisofdifferentCAPweresummarizedinTable1.Duringthe reaction, the pressure in thebatch reactor was measured by a manometer.Whenthereactionreachedthedesiredreactiontime, thereactor was freelycooled down to room temperature.Solid products were separated from liquid phase by ﬁltration using 0.45

m

mﬁlterpaper.Thentheywereair-driedat50!_C_for₄₈_h_before

furtheranalysesandcharacterizations.

Elemental analysis was carried out by inductively coupled plasma atomic emission spectroscopy (ICP-AES, HORIBA Jobin YvonUltima2apparatus).Infraredspectroscopy(IR)wascarried outusingaShimadzuFTIR8400Sspectrometerinthewavenumber range 4000–500cm"1_. _X-ray _diffraction _(XRD) _measurements

were carried out using a Phillips Panalytical X’pert Pro MPD diffractometer.Scanningelectronmicroscopy(SEM)observation wasperformedonaPhilipsXL30ESEMapparatus. Thermogravim-etry analysis (TG) was carried out with a SDTQ600 analyzer (TAInstruments)underairﬂow(100mLmin"1₎_with_the_heating

rateof20!_C_min"1_._The_amount_of_remaining_CaCO

3intheﬁnal

solidwascalculatedcorrespondingtotheobservedweightlossof CO2from610to720!C.

3. Results

3.1.Orthophosphatecomparison

Fig.1presentsXRDresultsofthesolidproductsobtainedfrom thereactionofcalcitewithfourorthophosphatesundersimilar reaction conditions. Inall cases, Ca-HA appeared as the main crystallinecalciumphosphate.Ontheotherhand,the decompo-sitionofcalcite wasdifferent fromeachotherorthophosphate. Under the reaction conditions used, orthophosphoric acid alloweddecomposingcompletelytheintroducedcalcite,because the signal of themain diffractionpeakof calcite at 29.4! _was

negligible (CAP–H pattern). For three alkali orthophosphates used,diffractionpeaksofremainingcalcitewereclearlyobserved, which indicates that the reaction of calcite and these

Table1

SynthesisconditionsofCAPfromCaCO3(100mmolor10g),alkaliorthophosphates,

andH3PO4 (66.7mmol);D isthemass ratioofwater tocalciteintheinitial

suspension.Theﬁnalpressureinthebatchreactorvariedintherangeof9–16bar. Orthophosphate T (!_C) t (h) D Water (g) Solidproduct designation Note NaH2PO4 80 48 13.5 135 CAP–Na Comparisonof

orthophosphate KH2PO4 80 48 13.5 135 CAP–K NH4H2PO4 80 48 13.5 135 CAP–N H3PO4 80 48 13.5 135 CAP–H H3PO4 60 48 4.5 45 T60/t48/D4.5 Parametric study H3PO4 60 48 9 90 T60/t48/D9 H3PO4 80 48 4.5 45 T80/t48/D4.5 H3PO4 80 48 9 90 T80/t48/D9 H3PO4 80 168 9 90 T80/t168/D9

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orthophosphateswasnotcompleted.Thisresultwasconfirmed byTGanalysis(resultsnotshown).Theremainingcalcitecontent presentinthefinalsolidswas4.4,1.4,0.5and<0.06wt.%forCAP– Na,CAP–K,CAP–NandCAP–H,respectively.Probably, orthophos-phoric acid with higher acidity compared to other alkali orthophosphates was more favorable for the dissolution of calcite particles,which is crucial for the formation of calcium phosphatephases [15].Whencalciteparticleswerecoveredby solid calcium phosphate layers, the contact between these covered calcite particlesandorthophosphatessourcesmust be preventedandsothereactionisstoppedorsloweddown[15,16]. Inadditiontothishigherperformanceforthedecompositionof calcite, nowashingstepwasneededfor thepurificationofthe solidproduct startingfromorthophosphoricacidthanks tothe absenceofcounter-ionssuchasalkalis.Soforthenextparametric

study,CAPsynthesiswasperformedonlywithorthophosphoric acid.

3.2.CAPfromcalciteandorthophosphoricacid–XRD characterization

Fig.2presentsXRDpatternsofthesolidproductsobtainedat different synthesis conditions. Both productsobtained at 60!_C

(T60/t48/D4.5andT60/t48/D9)containedoctocalciumphosphate (OCP, Ca8(HPO4)2(PO4)4

#

5H2O) as the main crystalline calcium

phosphate, and high contents of remaining calcite. So the temperatureof60!_C_was_not_enough_for_the_complete_dissolution

ofcalciteparticles.Probablythistemperatureledtotheformation ofcore–shellparticlesinwhichcalcitecorewascoveredbysolid calciumphosphatelayers(shell)[17].Thisstructurepreventedthe

Fig.2.XRDpatternsofthesolidproductsobtainedatdifferentsynthesisconditions;(&)Ca-HA(JCPDSstandardNo.01-072-1243);(~)OCP(JCPDSstandardNo. 00-026-1056);(*)calcite(JCPDSstandardNo.00-047-1743).

500 1000 1500 2000 2500 3000 3500 4000 Tr ansm ittance, a. u Wavenumber, cm-1 T80/t168/D9 T80/t48/D9 T80/t48/D4.5 T60/t48/D9 T60/t48/D4.5 OH Phosphate CO32 Phosphate CO32

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contact of remaining calcite core with phosphate species and sloweddownor stopped thereaction at this temperature. The increaseofthedilutionofcalcitesuspensiondidnotimprovethe dissolutionofcalciteat60!_C.

Onthe other hand, whenthe reaction temperature rose to 80!_C,_calcite_could_be_completely_dissolved_as_indicated_its_very

weak signal of the principal XRD peak at 29.4!_. _At _this

temperatureandforthesamereactiontimeof48h,thedilution ofCaCO3suspensionhadnoremarkableinﬂuenceontheformed

product.Themaincrystallinecalciumphosphatephaseidentiﬁed fortheproductssynthesizedat80!_C_was_Ca-HA._However,_CAP

(JCPDS standard No. 96-900-3550, 96-900-3551, 96-900-3552) mightbealsopresentintheseproductsbuttheirXRDdiffractions areusuallysuperposedonthoseofCa-HA.SothepresenceofCAP needstobeconﬁrmedbyotheranalyses.

3.3.CAPfromcalciteandorthophosphoricacid–IRcharacterization IRspectraofallthesolidproductsarepresentedinFig.3.Inall cases,characteristicpeaksofphosphategroupscouldbefoundin thewavelengthrangesof650–550cm"1_and_1300–910_cm"1_[13]_.

Fortwosolidsobtainedat60!_C,_no_signal_of_carbonate_groups_was

observed, despite remarkable contents of remaining calcite as shown by XRD analysis (Fig. 2). As mentioned above, calcite remnants must be covered by calcium phosphate layers and thereforecouldnotbedetectedbydiffusereﬂectanceIRanalysis, whichrecordsonlysurfaceinformationforsolidsamples.

For the solids synthesized at 80!_C, _absorption _bands _of

carbonategroupscouldbeclearlyobservedat1545,1450,1415, 880,and870cm"1_._All_these_absorption_bands_could_be_attributed

tocarbonate groups inserted in theapatite structure of Ca-HA

80

85

90

95

100

105

0

500 1000

1500

TG

(w

t.

%

)

Temperature,

o

_C

T60/t48/D4.5

T60/t48/D9

(A)

0

500

100

0

150

0 DT

G

(w

t.

%

/

o

C),

a

u

Temperature,

o

_C

T60/t48/D4.5

T60/t48/D9

(B)

Fig.4.TGanalysisofthesolidproductssynthesizedat60!_C.

80

85

90

95

100

105

0

500

100

0

150

0 TG

(w

t.

%

)

Temperature,

o

_C

T80/t168/D9

T80/t48/D4.5

T80/t48/D9

(A)

0

500

100

0

150

0 DT

G

(w

t.

%

/

o

C),

a

u

Temperature,

o

_C

T80/t168/D9

T80/t48/D4.5

T80/t48/D9

(B)

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[18–20].Carbonategroupsreplacedbothphosphateandhydroxyl groupstoformA-B-typeCAP,asillustratedbytheircharacteristic absorption bands at 1545 and 880cm"1 _(A-type) _and _1450,

1415and870cm"1_(B-type)_[18,19]_.

Theelementalanalysisofthreesolidproductsobtainedat80!_C

showedthatthemolarratioofcalciumtophosphorusvariedin 1.83–1.90 range, which was higher than the value of the stoichiometricCa-HA. Thiscanbeexplainedbytheinsertion of carbonategroupsatthepositionofphosphategroups.

3.4.CAPfromcalciteandorthophosphoricacid–TGcharacterization Fortheuseasbiomaterials,calciumphosphatebasedproducts areusuallytreatedbyasinteringstep[21].Thermalbehaviorofthe preparedsolidswasinvestigatedinlargerangeoftemperatureas showninFigs.4and5.Forthesolidpreparedat60!_C₍_Fig.₄_),_after

theﬁrstweightlossabout100!_C_due_to_the_removal_of_surface

humidity, different weight losses in the temperature range of 100–600!_C_were_observed_for_the_dehydration_of_OCP_[18,22–25]_,

which wasthemaincalciumphosphatepresentinthesesolids. Remainingcalciteshowedanintenseweightlossatabout610!_C,

followedbythedecarbonationofCAPat750!_C._No_further_weight

losswasobservedupto1200!_C_for_these_two_solids.

For the solids synthesizedat 80!_C, _after_the_dehydration _of

surface moisturearound 100!_C, _the_dehydration_of

hydrogeno-phosphate groupstook placein therangeof 100–600!_C. _These

weightlossesweremuchlowercomparedtothesolidssynthesized at 60!_C ₍_Fig. ₄_). _As _expected, _no _notable _signal _of _calcite

decomposition was detectedaround 610!_C. _On _the_other_hand,

thedecarbonationofCAPtookplacewithimportantweightlosses. Thisdecarbonationstartedatabout750!_C_and_ﬁnished_at_about

1200!_C. _The _last _weight _loss _around ₁₂₅₀!_C _was _due _to _the

dehydration of hydroxyl group of apatitic structure to form oxyhydroxyapatite[5].So,whenthesynthesistemperaturewasset at80!_C, _the_reaction_time_and _the_dilution _of_the_initial_calcite

suspensionhadnonotableinﬂuenceontheﬁnalCAP.Threesolid productssynthesizedat80!_C_seemed_also_to_have_similar_thermal

behavior.FromTGanalysis,thecontentofcarbonateinsertedinthe apatiticstructurecouldbecalculated,supposingthatweightloss in thetemperature range of750–1250 was due tothethermal decarbonation. Thus, three solid products synthesized at 80!_C

fromcalciteandorthophosphoricacidhadthecarbonatecontent intherangeof4.2–4.6wt.%.

3.5.CAPfromcalciteandorthophosphoricacid–thermaltreatment andbiomineralizationactivityinSBFsolution

For use as biomaterials, hydroxyapatite based products, includingCAP,mayneedstabilizationstepbythermaltreatment. InthecaseofCAP,thethermaltreatmentshouldnotleadtodeep decarbonation, in order tomaintain apatitic carbonate content similartothatofbonemineral[6].Inthissection,thermalstability ofCAPsynthesizedat80!_C_{(T80/t48/D4.5)}_is_discussed._This_solid

T80/t48/D4.5 was chosen because of its lowest content of remainingCaCO3.ThereactivityofsolidproductsinSBFtest,as

the biomineralization activity, is also reported. This test was carriedoutwithT80/t48/D4.5thermallytreatedatthe tempera-turerangeof105–1400!_C_under_air_atmosphere.

ThermaltreatmentofT80/t48/D4.5powderwascarriedoutin the TG–DSC analyzer under air atmosphere. The powder was heatedat10!_C_min"1_up_to_desired_ﬁnal_temperature_and_was_kept

atthis temperaturefor5h.The ﬁnaltemperature variedin the range600–1400!_C._After,_the_oven_was_freely_cooled_down_to_room

temperature. 500 700 900 1100 1300 1500 1700 Tr an sm itt an ce (a . u .) Wavenumber (cm-1₎ 105o_C 600 o_C 800 o_C 1000 o_C 1545 1450 1415 1200 o_C 1400 o_C

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IR spectrawere rapidlyrecorded onsinteredproducts, and are presented in Fig.6.Althoughthe decarbonationof CAPstarted around750!_C_(TG_analysis,_Fig.₅_),_the_thermal_treatment_in_the

temperaturerangeof600–800!_C_seemed_to_have_no_impact_on_the

carbonatecontentofT80/t48/D4.5solid.Thismaybeexplainedby alowkineticdecarbonationofT80/t48/D4.5at600–800!_C._When

thesinteringtemperatureroseto1000!_C,_a_partial_{decarbonation}

couldbeobserved,leadingtoreductionofIRintensityofapatitic carbonategroups.At1200–1400!_C,_absorption_bands_of_carbonate

groups disappeared, indicating that the decarbonation was complete. Thecalcinationat1200!_C_led_to_the_{characteristic}_IR

spectra ofCa-HA,while thecalcinationat 1400!_C _decomposed

Ca-HA intotetracalciumphosphate(TTCP)andtricalcium phos-phate(TCP)[18,26].Accordingtopreviousreports[18,19,26],the thermal treatmentunderairatmosphereisexpected toincrease the crystallinities of Ca-HA and CAP, and decrease the apatitic carbonatecontentofCAP,asconﬁrmedbyIRresults(Fig.6).Butat the very high temperature of 1200–1400!_C, _Ca-HA _and _CAP

decomposedintoTCPandTTCP.

Biomineralization activityof sinteredsolids wasinvestigated usingsimulatedbodyﬂuid(SBF)solution.SyntheticSBFsolution waspreparedaccordingtopreviouswork[27].Forthistest,asolid sinteredataspeciﬁctemperaturewassubmergedintoSBFsolution andtheobtainedsuspensionwasthermostatedat37!_C_for₇_days.

SEM studywas thenperformedonthepowdersrecoveredafter risingwithwateranddryingatroomtemperature.

Ontheleft-hand-sideof Fig.7,thesinteringat600–1000!_C

hadnosignificantinfluenceontheapparentmorphologyofCAP particles.Particlesofflat-needle-likemorphologydominatedCAP powders, driedat105!_C_or_sintered _at_600–1000!_C._When_the

temperature rose to 1200–1400!_C _{(left-hand-side,} _Fig. ₈_),

sintering took place with the increase of particle size, true density and the decrease of porosityandspeciﬁc surfacearea [28,29].

ForCAPpowderstreatedat105–1000!_C,_despite_the_decrease

ofcarbonatecontentwhenthecalcinationtemperatureincreased as showed by TGanalysis, CAP particles werecovered by new calcium phosphate layers after contact with SBF solution (Fig. 7, right-hand-side). Previous reports showed that Ca-HA basedmaterialshadappropriatebiomineralizationactivityforthe growthofcalciumphosphatelayersinSBFsolution[27,30,31].SBF solutionwasalsofoundasfavorablemediumfortheprecipitation ofcalcium andphosphate toformCa-HA [32,33].For oursolid synthesizedat80!_C,_the_presence_of_trace_amount_of _remained

calcitemustnotinﬂuencethegrowthofCa-HAbecausecalcitehas beenshownasbiomineralanditsgrowthtookplaceinSBFsolution [14,33]. For the solids calcined at 1200–1400!_C, _although _the

thermaldecarbonationwascomplete,thegrowthofnewcalcium phosphatelayersalsotookplace(Fig.8,right-hand-side).Infact, Ca-HA,andnon-apatiticcalciumphosphatesincludingTTCPand TCP, which resulted from thermal treatment of CAP at 1200–1400!_C, _are _also _known _as _active _{biomineralization}

materialsinSBFsolution[26,31,34,35]. 4. Conclusions

The reaction of calcite and different orthophosphates was investigated.Alkaliphosphatesdidnotallowacomplete decom-positionofcalciteat80!_C_in_a_close_batch_reactor.

Ontheotherhand,orthophosphoricacidledtothecomplete decompositionofcalcitepowder,andcarbonatedhydroxyapatite (CAP)wasformed.Thereactiontemperatureof80!_C_was_found_to

be crucial for the total decomposition of calcite and thus the formationofapatiticphase.Thereactiontimeandthedilutionof calcitesuspensionhadnosigniﬁcantinﬂuenceonthereaction.

CAPpowderstartingfromorthophosphoricacidandcalcitewas thermally stable at 600 and 800!_C _under _air _atmosphere. _At

1000!_C _for ₅_h, _partial _{decarbonation} _was _observed. _The

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decarbonationwastotalat1200orabove.AllCAPanditsthermal decompositionproductswerefoundtobereactiveinSBFsolution, promotingcrystallizationofbiomimeticapatites.

Acknowledgment

Theauthorsgratefullyacknowledgecolleaguesat RAPSODEE Centerfortechnicalhelp.

References

[1]E.D.M.D.Pellegrino,R.M.B.S.Biltz,Medicine44(1965)397–418.

[2]K.J.Quelch,R.A.Melick,P.J.Bingham,S.M.Mercuri,Archs.Oral.Biol.28(1983)

665–674.

[3]J.P.Bilezikian,L.G.Raisz,T.J.Martin,PrinciplesofBoneBiology,3rded.,Elsevier,

2008.

[4]E.S.Thian,Z.Ahmad,J.Huang,M.J.Edirisinghe,S.N.Jayasinghe,D.C.Ireland,R.A.

Brooks,N.Rushton,W.Bonﬁeld,S.M.Best,Biomaterials29(2008)1833–1843.

[5]D.PhamMinh,N.D.Tran,A.Nzihou,P.Sharrock,Mater.Sci.Eng.C33(2013)

2971–2980.

[6]E.Landia,G.Celottia,G.Logroscinob,A.Tampieria,J.Eur.Ceram.Soc.23(2003)

2931–2937.

[7]R.M. Wilson,J.C.Elliott,S.E.P.Dowker,R.I.Smith,Biomaterials25(2004)

2205–2213.

[8]S.Padilla,I.Izquierdo-Barba,M.Vallet-Regí,Chem.Mater.20(2008)5942–5944.

[9]H.E.Mason,A.Kozlowski,B.L.Phillips,Chem.Mater.20(2008)294–302.

[10]T. Tonegawa,T. Ikoma,Y.Suetsugu,N.Igawa,Y.Matsushita,T. Yoshioka,

N.Hanagata,J.Tanaka,Mater.Sci.Eng.B173(2010)171–175.

[11]W.L.Suchanek,P.Shuk,K.Byrappa,R.E.Riman,K.S.TenHuisen,V.F.Janas,

Biomaterials23(2002)699–710.

[12]D.PhamMinh,N.D.Tran,A.Nzihou,P.Sharrock,Ind.Eng.Chem.Res.52(2013)

1439–1447.

[13]D.PhamMinh,N.D.Tran,A.Nzihou,P.Sharrock,Mater.Res.Bull.51(2014)

236–243.

[14]M.Mozafari,F.Moztarzadeh,Challengesofspontaneousformationofcalcite

duringbioactivityassessmentonbioactivematerialsinterfaces,in:J.Dobrev,P.

Markovic (Eds.), Calcite: Formation, Properties and Applications, NOVA

SciencePubInc.,NewYork,2011,pp.95–122.

[15]D.PhamMinh,N.Lyczko,H.Sebei,A.Nzihou,P.Sharrock,Mater.Sci.Eng.B177

(2012)1080–1089.

[16]C.Verwilghen,M.Chkir,S.Rio,A.Nzihou,P.Sharrock,G.Depelsenaire,Mater.

Sci.Eng.C29(2009)771–773.

[17]D.PhamMinh,H.Sebei,A.Nzihou,P.Sharrock,Chem.Eng.J.198–199(2012)

180–190.

[18]J.C.Elliott,StudiesinInorganicChemistry18:StructureandChemistryofthe

ApatitesandOtherCalciumOrthophosphates,Elsevier,Amsterdam–London–

NewYork–Tokyo,1994.

[19]M.E.Fleet,X.Liu,Biomaterials28(2007)916–926.

[20]M.E.Fleet,Biomaterials30(2009)1473–1481.

[21]M.Jarcho,Clin.Orthop.Relat.Res.157(1981)259–278.

[22]A.I. Mitsionis, T.C. Vaimakis, C.C. Trapalis, Ceram. Int. 36 (2010)

623–634.

[23]H.Monma,Y.Nishimura,T.Okura,Phosph.Res.Bull.18(2005)127–134.

[24]A.Lebugle,E.Zahidi,G.Bonel,React.Solids2(1986)151–161.

[25]A.Bigi,G.Cojazzi,M.Gazzano,A.Ripamonti,N.Roveri,J.Inorg.Biochem.40

(1990)293–299.

[26]C.J.Liao,F.H.Lin,K.S.Chen,J.S.Sun,Biomaterials20(1999)1807–1813.

[27]S.Jalota,S.B.Bhaduri,A.C.Tas,Mater.Sci.Eng.C28(2008)129–140.

[28]S.Bailliez,A.Nzihou,Chem.Eng.J.98(2004)141–152.

[29]D.PhamMinh,M.GaleraMartinez,A.Nzihou,P.Sharrock,J.Therm.Anal.

Calorim.112(2013)1145–1155.

[30]T.Kokubo,S.Ito,M.Shigematsu,S.Sakka,T.Yamamuro,J.Mater.Sci.22(1987)

4067–4070.

[31]T.Kokubo,H.Takadama,Biomaterials27(2006)2907–2915.

[32]A.C.Tas,Biomaterials21(2000)1429–1438.

[33]M.Mozafari, F.Moztarzadeh, M.Tahriri, J. Non-Cryst.Solids 356 (2010)

1470–1478.

[34]K.Kurashina,H.Kurita,M.Hirano,J.M.A.deBlieck,C.P.A.T.Klein,K.deGroot,

J.Mater.Sci.:Mater.Med.6(1995)340–347.

[35]L.A.DosSantos,L.C.DeOliveira,E.C.S.Rigo,R.G.Carrodeguas,A.O.Boschi,