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In luence o Si subs i u ion on he eac i i y o α-T icalcium Phospha e
Ma iana Mo isuke1*, Gemma Mes es2, Ca oline O. Renó1, Raúl G. Ca odeguas3, Cecília A.
C. Za aglia4 and Ma ia-Pau Gineb a5
1 Bioce amics Labo a o y – Science and Technology Ins i u e, UNIFESP, 12231-280, São
José dos Campos, SP, B azil
2 Enginee ing Sciences Dp ., Uppsala Uni e si y, Box 534, 751 21 Uppsala, Sweden.
3 Depa men o Ce amics, Ins i u e o Ce amics and Glass (ICV), CSIC, Kelsen 5, 28049
Mad id, Spain
4 Labiomec – Mechanical Enginee ing School – S a e Uni e si y o Campinas, 13083-860,
Campinas, SP, B azil
5 Enginee ing Sciences and Me allu gy Dp ., Technical Uni e si y o Ca alonia, Diagonal
647, 08028 Ba celona, Spain.
* Co esponding Au ho :
Ma iana Mo isuke
330 Talim S ee - Vila Nai
São José dos Campos, SP - B azil
Zip Code: 12231-280
Tel.: +55 12 3309-95
Fax: +55 12 3921-8857
mo isuke@uni esp.b
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Abs ac
Silicon subs i u ed calcium phospha es ha e been widely s udied o e he las en yea s due o
hei enhanced os eogenic p ope ies. No wi hs anding, he ole o silicon on α-TCP eac i i y
is no clea ye . The e o e, he aim o his wo k was o e alua e he eac i i y and he
p ope ies o Si-α-TCP in compa ison o α-TCP. P ecu so powde s ha e simila p ope ies
ega ding pu i y, pa icle size dis ibu ion and speci ic su ace a ea, which allowed a be e
compa ison o he Si e ec s on hei eac i i y and cemen s p ope ies. Bo h Si-α-TCP and α-
TCP hyd olyzed o a calcium-de icien hyd oxyapa i e when mixed wi h wa e bu hei
con e sion a es we e di e en . Si-α-TCP exhibi ed a slowe se ing a e han α-TCP, i.e. kSSA
o Si-TCP (0.021 g.m-2.h-1) was almos ou imes lowe han o α-TCP (0.072 g.m-2.h-1). On
he o he hand, he comp essi e s eng h o he CPC esul ing om ully eac ed Si-α-TCP
was signi ican ly highe (12.80± 0.38 MPa) han ha o α-TCP (11.44 ± 0.54 MPa), due o
he smalle size o he en angled p ecipi a ed apa i e c ys als.
Key-wo ds: α- icalcium phospha e, calcium phospha e cemen , kine ics, silicon.
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1. In oduc ion
Calcium phospha e cemen s (CPCs) we e disco e ed in he 1980's by B own, Chown and
LeGe os [1,2]. These ma e ials a e s ill ac i ely s udied nowadays since CPCs p esen
a ac i e cha ac e is ics such as bioac i i y, biocompa ibili y, os eoconduc i i y and
eso babili y [3,4]. Fu he mo e, CPCs consis on a moldable pas e ha can be injec ed in o
he bone de ec using minimally in asi e p ocedu es [5–7], wi h in i o sel -se ing a e a
ew minu es.
The wo mos common ypes o CPCs ha e been called upon he end-p oduc o med: apa i e
cemen (p ecipi a es a pH > 4.2) and b ushi e cemen (p ecipi a es a pH < 4.2). One o he
mos common main p ecu so o apa i e cemen s is α- icalcium phospha e (α-TCP) [8],
which dissol es and p ecipi a es in o calcium de icien hyd oxyapa i e when mixed wi h
wa e ia a cemen i ious eac ion.
Se e al s udies ha e shown ha i is no so easy o ob ain a highly pu e α-TCP [8–11]. The
eason o ha has been asc ibed o he p esence o magnesium impu i ies in mos
comme cial eagen s, a well-es ablished s abilize o β-TCP, a lowe empe a u e isomo ph o
TCP [10,12–14]. When Mg2+ is p esen a ≥ 4.1 a .% he empe a u e o β→α phase
ans o ma ion can inc ease om ~1125°C o 1485°C [10,12,15–17]. The empe a u e o α-
TCP syn hesis can be educed by using Mg- ee eagen s [8,11,18,19]. Ca doso e al. [11] and
Mo isuke e al. [18,19] succeeded in ob aining α-TCP using impu i y- ee eagen a a
empe a u es o 1165ºC and 1300ºC, espec i ely. On he o he hand, Si has been shown o
s abilize he α phase down o low empe a u es [20,21]. The e o e, ano he pa h o educe he
empe a u e o α-TCP syn hesis is by doping α-TCP wi h silicon (Si-α-TCP). The
empe a u es o syn hesizing Si-α-TCP may a y om 700ºC o 1250º depending on he
con en s o Mg and/o o he impu i ies [9,22–26].
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Si-α-TCP can be ob ained by ea ing a high empe a u es a p ecipi a e ob ained a e mixing
calcium ni a e and ammonium phospha e solu ion a a p ope a io in he p esence o
ammonia and ei he colloidal silica o o ganic silicon compounds [23,27]. An al e na i e
ou e consis s in pe o ming a solid s a e eac ion o mix u es o 1) CaCO3, CaHPO4 o
(NH4)2PO4, and Ca2SiO4 o CaSiO3 [9,28], o 2) β-Ca3(PO4)2 and CaSiO3 [29], o 3) HA and
SiO2 [26].
When calcium phospha e cemen s a e p epa ed om a Si-α-TCP powde some cemen
p ope ies a e al e ed as compa ed o i s pu e coun e pa . One example is powde solubili y.
Acco ding o Wei e .al. [30], Si inc eases α-TCP solubili y. Mes es e .al. [31] e i ied a
as e hyd olysis kine ics, he cemen wi h Si p esen a simila esis ance when compa ed wi h
he pu e, a dec ease in cell p oli e a ion and an inc eased in alkaline phospha ase (ALP)
ac i i y, which co esponds o an enhance o cell di e en ia ion. On he o he hand, Cami é
e .al. [28] obse ed a dec ease on powde eac i i y and cemen mechanical s eng h and; an
inc eased os eoclas ic and os eoblas ic ac i i y.
Addi ionally o he s abiliza ion o α-TCP phase, silicon has been shown o be bene icial o
some biological p ope ies such as bone calci ica ion [32]. Si is essen ial o bone
egene a ion and he e o e can s imula e ce ain cell ac i i ies such as p oli e a ion and
di e en ia ion o os eoblas s [26]. Mo eo e , he bioac i i y o a ma e ial can be imp o ed by
doping i wi h Si [33–35].
The ole o silicon on he eac i i y o α-TCP owa ds he o ma ion o CPCs is no clea ye
[19,26,28]. Thus, he aim o his wo k was: 1) o e i y how silicon may in luence on he
se ing eac ion o α-TCP bone cemen ; and 2) o de e mine how he di e en eac i i y
a ec s he physico-chemical p ope ies o CPCs. The no el y o his wo k elies on he use o
Mg- ee p ecu so s o p epa ing α-TCP and Si-α-TCP [9] and on he a emp o employ
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easible and la ge scale p ocedu es o p omo e he p oduc ion o mo e accessible bone
cemen s.
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2. Ma e ials and me hods
2.1 P epa a ion o TCP powde s and bone cemen
α-TCP and Si-α-TCP we e syn hesized by a solid s a e eac ion om he app op ia e mix u e
o lab made Mg- ee CaCO3 (Mg w -% < 0.0180), CaHPO4 (Mg w -% < 0.0001) and CaSiO3
(Mg w -% < 0.0001) as desc ibed elsewhe e [9]. B ie ly, CaCO3 and CaHPO4 we e mixed o
p epa e α-TCP, and 2 w .% o CaSiO3 was included in he mix u e o p epa e Si-TCP. The
powde s we e calcined o 6 h a 1300ºC o α-TCP and 1200ºC o Si-TCP wi h a hea ing
a e o 10ºC.min-1. A e wa ds, samples we e le o cool down inside he u nace wi hou
quenching. Finally, he powde s we e milled in a ho izon al ball mill o 48 h using an
alumina g idding media o Ø15 mm and ball o powde a io o 20:1 w/w.
The mixing liquid used in cemen s was an aqueous solu ion o Na2HPO4 (2.5 w .%) and
C6H8O7 (ci ic acid) (1.5 w .%) in dis illed wa e . Ci ic acid was employed as a liquid educe
agen and o p omo e a mo e homogeneous se ing eac ion due o i s dispe san e ec [36],
and Na2HPO4 was added o accele a e he se ing eac ion due o he coomon-ion e ec [37].
Cemen s we e p epa ed by mixing he powde and liquid in a a io (L/P) o 0.60 mL.g-1. The
pas e was in oduced in Te lon molds (6 mm diame e x 12 mm heigh ), and samples we e
imme sed in 0.9 w .% o NaCl solu ion a 37 ºC o se ing.
2.2 Cha ac e iza ion o physico-chemical p ope ies
X-Ray Fluo escence (XRF, Philips, MagiX Supe Q Ve sion 3.0) was used o e alua e he
elemen al composi ion (majo and mino componen s), as well as Ca/P o Ca/(P+Si) a ios o
he wo TCP powde s. X-Ray Di ac ion (XRD, B uke D8 Ad ance, CuKα, Ni il e , 20 o
40º (2θ), 0.02 º s-1, 40kV and 40mA) was also used o quali a i e and quan i a i e
de e mina ion o he c ys alline phases exis ing in he s a ing powde s and se cemen s.
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JCPDS iles used o phase iden i ica ion we e #09-0348 o α-TCP and #09-0169 o β-TCP.
Fo quan i a i e de e mina ion o β-TCP on he s a ing powde s he in e nal s anda d me hod
was employed, in which a di ac ion line om he phase quan i ied (β-TCP) was compa ed
o a di ac ion line om a s anda d (Al2O3) mixed wi h he sample in known p opo ions
[38].
The densi y o he TCP powde s was measu ed by helium picnome y (Mic ome i ics,
AccuPyc 1330), he speci ic su ace a ea (SSA) was measu ed by ni ogen adso p ion
(Mic ome i ics, ASAP 2020) acco ding o B unaue -Emme -Telle heo y and he
g anulome y o he powde was de e mined by lase di ac ion pa icle size analysis (Coul e
Coun e LS 13 320).
The ha dening kine ics was moni o ed by measu ing he comp essi e s eng h (MTS, Tes
S a II) o we samples a e di e en ime in e als (2, 4, 8, 24, 72, 120, 168, 360 h), a leas
10 cylind ical specimens we e es ed pe condi ion. A e ha , samples we e imme sed in
ace one o 2h o s op he se ing eac ion, and hen d ied a 100ºC o e nigh . The c ys alline
phase composi ion a each ime poin was assessed by XRD, (including a JCPDS ile #46-
0905 o CDHA). The con e sion a e was de e mined by XRD ollowing he p ocedu e
p oposed by Gineb a e al. [39,40] and Rigo e al. [41]. I is known ha he mass ac ion o a
c ys alline ma e ial p esen in a gi en sample is p opo ional o hei XRD lines in ensi ies.
To e alua e he e olu ion o he se ing eac ion o he cemen s s udied, he a e o α-TCP
con e sion (α ) was e alua ed based on he e olu ion o i s mass ac ion wi h ime as s a ed
on Equa ion 1.
𝛼𝑡=(𝑤0−𝑤∞)−(𝑤𝑡−𝑤∞)
(𝑤0−𝑤∞) Equa ion 1
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Whe e w0 is α-TCP mass ac ion a ini ial ime ( = 0 h), w
∞
is α-TCP mass ac ion a e
he 168h o se ing eac ion and w is α-TCP mass ac ion a a de e mined ime, . A each
ime, α-TCP mass ac ion was de e mined a e i s XRD lines (1 3 2), (1 1 3) and (1 0 7)
in eg a ed in ensi ies (Equa ion 2) and an a e age alue was es ablished.
𝐼𝛼
𝐼𝛼,0 =𝑤𝛼𝑀𝛼
𝑤𝛼,0[(𝑀𝛼−𝑀𝐶𝐷𝐻𝐴)(𝑤𝛼+𝑤𝛽)+𝑀𝐶𝐷𝐻𝐴] Equa ion 2
Whe e Iα is he in eg a ed in ensi y o α-TCP (1 3 2), (1 1 3) o (1 0 7) XRD lines a a
de e mined ime, ; Iα,0 is he in eg a ed in ensi y o α-TCP (1 3 2), (1 1 3) o (1 0 7) XRD
lines a ini ial ime ( = 0h); Mα is he is he mass abso p ion o α-TCP, 86.43 [40]; MCDHA is
he mass abso p ion o CDHA, 84.97 [40]; wß is he mass ac ion o ß-TCP du ing se ing
eac ion; wα is he mass ac ion o α-TCP a a de e mined ime, and; wα,0 is he mass
ac ion o α-TCP a ini ial ime ( = 0h). In his s udy, he ex e nal pa e n me hod was
employed [38]. The ex e nal pa e n used in his wo k was β-TCP which is p esen in all
samples and do no pa icipa e on he se ing eac ion, hus, i s mass ac ion is cons an
du ing all he p ocess [5,39,40].
Mo eo e , he e olu ion o he speci ic su ace a ea and he mic os uc u e du ing he se ing
eac ion was assessed by N2 adso p ion and scanning elec on mic oscopy (SEM, JEOL-6400)
espec i ely.
2.3 S a is ics
One-way analysis o a iance (ANOVA) and 2 sample - es s we e pe o med o compa e
di e ences be ween he mean alues o samples’ comp essi e s eng h using a con idence
le el o 95 %. In ANOVA analysis, Tukey’s compa ison pos hoc es was pe o med o
assess di e ences in each pai o means. No mali y and equal a iances es s we e conduc ed
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p io o ANOVA o gua an ee ha da a ollowed No mal dis ibu ion and p esen ed
homoscedas ici y.
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Figu es Cap ion
Fig. 1 XRD pa e ns o TCP powde s. Legend: α = α-TCP.
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Fig. 2 XRD pa e ns o he kine ics s udy o Si-α-TCP and α-TCP. Legend: α = α -TCP, ß =
ß-TCP, A = apa i e, * = (1 0 7) di ac ion line o α-TCP.
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Fig. 3 TCP con e sion (α ) as a unc ion o ime.
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Fig. 4 E olu ion o comp essi e s eng h wi h ime. The legends indica e he ime poin s in
hou s.
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