ARTICLE IN PRESS

Biomaterials 24 (2003) 41234131

Mechanical activation and cement formation of b-tricalcium

phosphate
U. Gburecka,*, O. Grolmsa, J.E. Barraletb, L.M. Groverb, R. Thulla
a

Department for Functional Materials in Medicine and Dentistry, University of Wurzburg,

Pleicherwall 2, Wurzburg
D-97070, Germany
.
.
b
Biomaterials Unit, School of Dentistry, University of Birmingham, St. Chads Queensway, Birmingham B4 6NN, UK
Received 13 December 2002; accepted 8 April 2003

Abstract
The reactivity of acid base cements forming hydroxyapatite (HA) such as, tetracalcium phosphate, and dicalcium phosphate
anhydride or dicalcium phosphate dihydrate, is normally adjusted by altering the particle size and hence the specic surface area of
the compounds. Amorphous calcium phosphates, prepared by precipitation from supersaturated solutions, can also react to form
apatitic cements since they are thermodynamic unstable with respect to HA and have a setting reaction more independent of particle
size. In this report we show for the rst time that prolonged high-energy ball milling of b-tricalcium phosphate (b-TCP), led to
mechanically induced phase transformation from the crystalline to the amorphous state. The process increased the thermodynamic
solubility of the b-TCP compared to the unmilled material by up to nine times and accelerated the normally slow reaction with
water. By using a 2.5% Na2HPO4 solution setting times were reduced to 516 min rather than hours. X-ray diffraction analyses
indicated that the amorphous fraction within the materials was responsible for the primary setting reaction and hardening of the
cements, while the crystalline fraction remained unreacted and converted only slowly to HA. Mechanically activated b-TCP cements
were produced with compressive and diametral tensile strengths of up to 50 and 7 MPa respectively. The effect of preparation and
setting parameters on the physical and chemical properties of mechanically activated b-TCP cement was investigated.
r 2003 Elsevier Science Ltd. All rights reserved.
Keywords: Calcium phosphate cement; X-ray diffraction; Mechanical properties; b-tricalcium phosphate; Phase transformation; Porosity;
Hydroxyapatite

1. Introduction
Calcium phosphate cements (CPC) are used clinically
in cranio- and maxillofacial surgery for lling non-load
bearing bone defects [13]. The cements are usually
based on acidbase reactions between several calcium
orthophosphate combinations and set in situ in the
presence of an aqueous phase. Cement formation is
based on the pH dependent solubilities of calcium
phosphates [4]. Two types of cements are distinguishable, cement formed at pHo4.2, which are obtained
using acidic calcium phosphates or phosphorous acid,
form brushite (DCPD, CaHPO4
2H2O) [5,6] and above
4.2, hydroxyapatite (HA) is formed.
*Corresponding author. Tel.: +49-931-201-73550; fax: +49-931201-73500.
E-mail address: uwe.gbureck@fzm.uni-wuerzburg.de
(U. Gbureck).

Reactants for HA cements are crystalline calcium

phosphates like tetracalcium phosphate (TTCP) [79] or
a/b-tricalcium phosphate (TCP) [1013] combined with
slightly acidic compounds like dicalcium phosphate
anhydride (DCPA) or dicalcium phosphate dihydrate
(DCPD). Because of different rates of dissolution of
reactants, a setting reaction will only occur if the kinetic
solubilities of all components are congruent, hence this
is normally adjusted via the particle size/specic surface
area of the reactant particles [14,15]. Another mechanism of HA cement formation involves the crystallization
of metastable amorphous calcium phosphates. This
system has a setting reaction independent of particle
size due to the thermodynamic instability of the reactant
with regard to HA [16]. Amorphous Ca/Ps are be made
by a precipitation process at high levels of supersaturation followed by freeze-drying of the product [17].
Another technique, known for the production of
amorphous metals or ceramics namely high-energy ball

0142-9612/03/$ - see front matter r 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0142-9612(03)00283-7

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

4124

milling [18,19], is not yet described in the literature for

the preparation of ACPs. And the application of ACP
made by mechanical transformation for cement formation has not been previously reported.
The aim of this work was to investigate the physical
and chemical behaviour of a new apatite cement system,
made from mechanically activated b-tricalcium phosphate (MAbT). The effect of ball milling b-TCP in
ethanol for up to 24 h on crystallinity and reactivity were
investigated. The setting reaction of mechanically
activated b-TCP with a near neutral Na2HPO4 solution
was examined and mechanical performance was monitored as a function of in vitro incubation time.

2. Materials and methods

b-Tricalcium phosphate (b-TCP) was synthesized by
heating a mixture of monetite (DCPA; Mallinckrodt
Baker, Griesham, Germany) and calcium carbonate
(CC; Merck, Darmstadt, Germany) to 1050 C for 24 h
followed by quenching to room temperature in a
desiccator. The product consisted of phase pure and
highly crystalline b-TCP as veried by X-ray diffraction
(XRD).
The sintered cake was crushed with pestle and mortar
and passed through a 355 mm sieve. Milling was
performed in a planetary ball mill (PM400 Retsch,
Germany, diameter: 400 mm), unidirectionally at
250 rpm with 500 ml agate jars, 200 agate balls
(10 mm) and a load of 125 g b-TCP and 125 ml ethanol
(99.9%), per jar. The ground powder was dried in a
vacuum oven at 60 C. In order to determine whether bTCP origin was critical, commercially available material
(Plasma Biotal, Derbyshire, UK), was also ground for
4 h using the same regime except only 15 g of material
was used.
The particle size distribution was determined using a
laser particle size analysis (L300, Horiba, Kyoto,
Japan). Hundred milligrams of the powder particles
was suspended in 200 ml isopropanol and dispersed by
applying ultrasound for 15 min.
The relative crystallinity of the MAbT samples were
calculated from X-ray diffraction patterns according to:
Relative crystallinity 100  Amilled sample =Arecryst: sample
 100%;
where A are the areas of the b-TCP reection peaks at
31.1 2y after milling (Amilled sample ) and thermal recrystallization (Arecryst: sample ). Because of the dependence of
the peak intensity (area) on the powder density of the
sample, a reference for each sample of MAbT was
synthesised by recrystallisation of the samples at 1050 C
for 2 h.
The measurement of the solubilities of the MAbTs
was performed by means of ion-selective potentiometry

at 37 C. An electrochemical cell was established using a

Ca2+sensitive calcium ion electrode (Mettler-Toledo,
GieXen, Germany) and a potential-constant Ag/AgClreference electrode (type InLab302, Mettler-Toledo,
GieXen, Germany). The free Ca2+ ion concentration in
the solution as a function of immersion time up to
60 min was measured. The cell was calibrated with
standard calcium solutions in the range between 106
and 101 mol Ca2+. For measuring the solubility of the
materials 2 ml of a 2 m ammonium chloride solution was
added to 100 ml deionized water to keep the activity
coefcients and the ion strength constant within the
electrolyte and 500 mg of powder was added while
stirring.
The cement was produced by the mixture of MAbT
and 2.5 wt% Na2HPO4 solution. Setting experiments
were also performed using deionized water as liquid
phase. Depending on grinding time it was found that
different powder to liquid (P:L) ratios gave workable
pastes of similar consistency as determined qualitatively
and were between 2.7 and 2.4 g/ml. A series of cements
made from MAbT ground for 24 h was made with P:L
ratios of 2.42.7 g/ml, in order to determine the effect of
porosity on the mechanical characteristics of the cement.
Samples were prepared by mixing the powder (800 mg
for compressive testing, 200 mg for DTS-testing) with
the required liquid volume in a nitrile rubber mixing
container on a vibratory shaker for 15 s. The cement
paste was transferred to stainless steel molds (6 mm in
diameter), both ends were closed with suitable stainless
steel plungers and pre-compressed by means of a
cantilever device described in the literature [20] at a
pressure of 9 MPa for 5 s, followed by a constant load of
0.7 MPa. After storing the whole apparatus for 2 h in a
37 C/100% humidity box, the specimens were removed
from the molds and stored in saturated calcium
phosphate solution for an additional 22 h. Sample
dimensions were 12  6 mm2 for compressive testing
and 3  6 mm2 for DTS specimens (n 6).
X-ray diffraction patterns of the starting b-TCP,
MAbT and set cements were recorded on a diffractometer D5005 ( D5005, Siemens, Karlsruhe, Germany).
Data were collected from 2y 20240 with a step size
of 0.02 and a normalized count time of 1 s/step. The
phase composition was checked by means of JCPDS
reference patterns for b-TCP (PDF Ref. 09-0169) and
HA (PDF Ref. 09-0432).
Crystal sizes and quantitative phase compositions of
the materials were calculated by means of total Rietveld
renement analysis with the TOPAS software (Bruker
AXS, Karlsruhe, Germany). As references the system
internal database structures of b-TCP and HA were
used together with a Chebychev forth-order background
model and a Cu Ka emission prole [21].
The initial setting time of the cement was measured in
a humidity chamber at 37 C and >90% humidity using

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

the Gilmore needle test with a needle of 113.98 g and

2.117 mm diameter according to ASTM standard [22].
Samples (n 6 per condition) with an aspect ratio of
2:1 were tested in compression at a crosshead speed of
1 mm/min using a static mechanical testing machine
Zwick 1440 (Zwick, Ulm, Germany) and a 5 kN load
cell. The diametral tensile strengths of the cement were
found by compressing each sample (6 mm diameter,
3 mm height), which was placed on its side between two
stainless steel plates, at a crosshead speed of 10 mm/min
until failure. The DTS was calculated from:
DTS MPa 2Fmax =p  d  l;
where d=diameter (6 mm), l=length of the sample
(measured) and Fmax is the failure load.
The strut densities of the cement, i.e. the densities of
the solid cement products were found using helium
pycnometry (Accupyc 1330, Micromeritics, UK). The
average densities of six cement samples were calculated
using 10 purges and 10 measurements. The dry bulk
densities of the milled powders were measured by
determining the settled volume of a known mass of
dry powder after vibration. These data combined with
mass and dimension measurements enabled calculation
of relative porosity of the cement. The distribution of
pore sizes in the cement between 60 mm and 6 nm was
measured using mercury porosimetry (Micromeritics
9420, UK).
The fracture surfaces were subsequently examined
using a scanning electron microscope (DSM 940, Zeiss,
Oberkochen, Germany). Samples were gold sputtered
and then images taken in high vacuum mode at an
accelerating voltage of 15 kV.

4125

30% of that of the raw material. After 8 h the median

particle size d50 reached a limit of about 3 mm. In
addition the average crystal size, calculated by the
TOPAS software on the basis of the peak broadening in
X-ray diffraction patterns, decreased from 233 nm for
the raw material to 25.5 nm after 24 h milling. At the
same time, the intensities of the b-TCP reection peaks
strongly decreased with prolonged grinding due to a
crystalline to amorphous phase transformation (Fig. 1).
The relative crystallinities of the materials compared to
the sintered raw material decreased continuously to 26%
after 24 h. The bulk density of the powder reached a
maximum after 1 h milling (1.05 g/cm3 cf bulk density of
Intensity / cps

1h

2h

4h

8h

3. Results

12h

The median particle sizes of the b-TCP as determined

by light scattering after milling are listed in Table 1. The
starting b-TCP material before grinding shows a median
particle size of 15 mm, which is typical for sintered and
manually crushed calcium phosphates. The particle size
of MAbT decreased with prolonged milling time. One
hour grinding by means of a ball mill reduced the size to

24h
20

25

30

35

40

2 Theta /
Fig. 1. X-ray diffraction patterns of b-TCP after milling in ethanol for
various time periods.

Table 1
Inuence of milling time in ethanol on the particle size, relative crystallinity and average crystal size, bulk and powder densities of b-TCP
Milling time (h)

Median particle
size, d50 (mm)

Relative
crystallinity (%)

Average crystal size

(nm)

Dry bulk density

(g/cm3)

Powder density
(g/cm3)

Unmilled
1
2
4
8
12
24

15.30
4.572
3.983
2.964
2.622
2.789
2.796

99.8
85.8
81.7
72.9
61.3
53.2
26.3

233.077.9
154.874.2
136.174.3
89.372.6
57.771.5
41.871.0
25.571.0

0.7970.01
1.0570.07

0.9870.06

0.7870.06

3.0470.02
3.0770.01

3.0770.02

2.9870.02

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

4126

Ca2+ -concentration (mol/l)

0.020

Intensity / cps

24h

0.015

4h

HA

HA

0.010

1h
1h

0.005

unmilled
0.000
0

50

100

150

200

250

2h

300

time/s

Fig. 2. Solubility of b-TCP after milling in ethanol.

4h
3

unmilled powder; 0.79 g/cm ), any further grinding of

the powder resulted in a decrease in its bulk density.
Fig. 2 shows the time dependant variation of the
calcium ion concentration in an aqueous electrolyte
after addition of several MAbT powders. The b-TCP
raw material leads to a maximum Ca2+ ion concentration of about 2 mmol/l within the electrolyte after 200 s.
Prolonged grinding of b-TCP increased the calcium
concentration to values of 7 mmol/l (1 h grinding),
13 mmol/l (4 h grinding) and 18 mmol/l after 24 h
grinding in ethanol. Except during the initial period of
dissolution (020 s), dissolution of MAbT was higher
after longer grinding times.
The X-ray diffraction pattern of cement made from
MAbT milled for 1 h demonstrated that 24 h after
setting, only weak HA-peaks could be observed (Fig. 3).
However the intensity of the HA peaks increased as
milling time of the reactants increased. The calculated
HA-contents of the cement samples after various setting
periods with a 2.5% Na2HPO4 solution according to the
Rietveld renement qualitative analysis is given in Table 2.
After 24 h setting at 37 C the HA content of the 1 h
ground b-TCP was about 19wt%. The quantity of HA
increased dramatically with grinding time and reached a
maximum for the 24 h ground sample, nearly 93wt%.
Using water only as liquid phase, a slow setting
reaction and hardening of the mechanically activated bTCP cement pastes occurred. The 24 h ground material
hardened within 5 h at 37 C, while the MAbT ground
for 4 h took about 8 h to form a mechanical stable
cement structure when set with water alone. The 1 h
milled MAbT was still paste-like 24 h after mixing with
water. The b-TCP raw material had no setting reaction
with water or Na2HPO4 solution after 24 h. Table 3
shows the properties of the MAbT after setting with a
2.5% Na2HPO4-solution for 24 h. An increase in milling
time resulted in a decrease of the initial setting time from
16 min (1 h milling) to 5 min (24 h milling).
Table 3 shows that both compressive and diametral
tensile strengths increased as a function of grinding time
of the cement reactant, such cement made with MAbT

8h

12h
24h
20

25

30

35

40

2 Theta /
Fig. 3. X-ray diffraction patterns of b-TCP milled in ethanol for
various time periods after 24 h setting with a 2.5% Na2HPO4 solution.

ground for 1 h, had compressive and tensile strengths of

7.4 and 1.4 MPa respectively, and after 12 h grinding,
these strengths had increased more than fourfold.
Grinding for a further 12 h did not increase either the
compressive or tensile strengths. Milling time dramatically reduced initial setting time from 16 to 7 min after 1
and 4 h, respectively, further milling made little or no
difference to setting time.
In order to determine whether mechanical properties
were sensitive to P:L ratio, the compressive strength of
cement was determined with MAbT ground for 24 h
made with P:L ratios between 2.4 and 2.7 mg/ml,
(Table 4). It can be seen that over this range of P:L
ratios, the compressive strength of the cement was
between 47 and 53 MPa and no correlation between
compressive strength and P:L ratio was observed.
Table 5 shows the deviation of the compressive
strength of the cement made from MAbT milled for 1,
4 and 24 h after setting with a 2.5% Na2HPO4 solution
at 37% over a period of up to 28 days (Fig. 4). The
strengths for the 1 and 4 h milled samples increased with
storage time, while there was almost no change for the
24 h milled b-TCP. The crystalline fraction of the 1 and
4 h milled cements slowly converted to CDHA with
ageing time (Table 5). In contrast, the 24 h milled b-TCP

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

4127

Table 2
HA content of cement samples after setting with 2.5% Na2HPO4 solution for 24 h
Grinding time (h)

12

24

HA content of cement (%)

19.2

25.0

41.4

59.7

85.8

92.7

Table 3
Setting times and mechanical properties of MAbT cements
Milling time (h)

P/L-ratio

Initial setting time (min)

Compressive strength (MPa)

Diametral tensile strength (MPa)

1
2
4
8
12
24

2.7
2.7
2.6
2.6
2.4
2.4

16
9
7
7
5
5

7.470.7
12.471.6
21.472.1
33.472.9
47.075.9
51.076.9

1.470.1
2.570.3
3.870.6
4.870.8
5.871.3
5.972.3

Table 4
Compressive strengths (MPa) of the 24 h ground cement formulated with different P/L ratios
Compressive strength (MPa) at P/L (mg/ml)
2.4:1
51.976.9

2.6:1
46.777.0

2.7:1
52.679.0

Table 5
Compressive strengths of b-TCP milled for 1, 4 and 24 h, after setting with a 2.5% Na2HPO4 solution for up to 28 d; HA content in parentheses
Milling time (h)

1
4
24

Compressive strength after ageing (MPa) (HA content (%))

1d

3d

7d

14 d

28 d

7.470.7
(19.2)
21.472.1
(41.4)
51.076.9
(92.7)

13.372.3

27.873.3

55.876.5

16.272.2
(36.8)
33.273.8
(59.0)
50.475.8
(98.6)

20.371.9
(44.2)
38.771.7
(58.5)
50.975.2
(99.2)

22.272.8
(47.1)
42.472.9
(60.8)
51.576.8
(98.5)

was almost completely set, (converted to HA) after 24 h

hardening and therefore showed no change in mechanical strength.
Increases in the grinding period only resulted in
decreases in the strut density of the cement from
3.1770.6 g/cm3 after 1 h of grinding to 2.9870.02 g/
cm3 after 24 h of grinding (Table 1). The use of ner
ground powder also resulted in the production of
cement containing less porosity; by increasing the
grinding period from 1 to 24 h the porosity present in
the cement was decreased by B5% (Table 6).
Approximately 50% of the pores present in
the cement produced using b-TCP ground for 1 h
were 6150 nm in diameter. An increase in the
grinding period resulted in a decrease in the range of

pore diameters present in the cement such that after

4 and 24 h grinding B50% of pores were 645 and
611 nm in diameter, respectively (Fig. 5). The
presence of larger pores of diameter 360 mm were also
detected in cement produced from b-TCP ground for
1 and 24 h.
Fig. 6 shows SEM-micrographs of the 1, 4 and 24 h
ground samples after 24 h setting at 37 C (fractured
surfaces of DTS-samples). The structure of the 1 h
ground sample essentially consisted of unreacted bTCP-particles, which were bound together by small (50
200 nm) needle-like crystals. The structure of the 24 h
ground samples was consisted mostly of spherical
crystals in the 100200 nm range which form larger
structures in the mm range.

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

4. Discussion
It is reported that b-TCP can slowly hydrolyse to
calcium decient HA as shown in Eq. (1) [23]. In this
report we show for the rst time, that following
mechanical activation by prolonged milling this reaction
can be accelerated to the point where a setting cement
system can be formed:
3b-Ca3 PO4 2 H2 O-Ca9 PO4 5 HPO4 OH:

The effect of mechanical activation could not be

attributed only to a decrease of the particle size but to a
mechanically induced phase transformation from the
crystalline to the amorphous state. This phenomenon is
already known for a number of compounds in the eld
of metallurgy and ceramics [18,19]: at a critical particle
Intensity / cps

24 h

4d

0.07

7d

14 d

28 d

20

25

30

35

size, the milling energy can no longer reduce particle

size, but leads to the formation of defects within the
crystal lattice. This process results in the formation of
nanocrystals within a single particle and therefore to a
loss of crystallinity of the material as a whole. As shown
in Fig. 1 some of the b-TCP converted to an amorphous
state, which can be seen as a decrease of the peak
intensities of X-ray diffraction patterns. The peak at
26.7 2y in the diffraction patterns of the 12 and 24 h
milled samples is thought to have resulted from wear of
the agate (SiO2) balls and jars and might be prevented
by the use of more wear resistant milling equipment.
Biomaterials investigations into mechano-processing
have focused on the mechanochemical reaction between
acidic calcium phosphates (MCPM) and basic salts like
TTCP or calcium oxide in solid phase [24,25]. The
authors of these reports showed that a solid state
chemical reaction occurred by treating the powder
mixtures in a ball mill without the involvement of an
aqueous phase. The reaction followed a rst-order
kinetic in dependence of number and weight of the
balls and the rotation speed of the ball mill. Based on
their results the authors assumed a reaction mechanism
via amorphous intermediates, but they did not present
direct evidence for this. Matsuya et al. [26] noticed a
continuous decrease of the crystal size from 80 to 60 nm
during dry milling of TTCP over a period of 5 h. At the
same time the number of lattice defects increased.
Polymeric cements based on milled TTCP and (polymethylvinyl-ether-)-maleic acid tended to result only
in a slight change in the mechanical properties but a

40

2Theta /

Incremental intrusion volume (ml/g)

4128

1h grinding
0.06

4h grinding

0.05

24h grinding

0.04
0.03
0.02
0.01
0
0.001

0.01

0.1

10

100

Pore diameter (m)

Fig. 4. X-ray diffraction patterns of the 4 h milled b-TCP sample after

hardening with a 2.5% Na2HPO4 solution for up to 28 d.

Fig. 5. The pore size distribution of cements produced using b-TCP

ground for 1, 4 and 24 h.

Table 6
The apparent densities, strut densities and calculated and measured relative porosities of cements produced with b-TCP ground for 1,4 and 24 h
Period of grinding (h)

Apparent density (g/cm3)

Strut density (g/cm3)

Calculated porosity (%)

Relative porosity (%)

1
4
24

1.7370.06
1.6570.02
1.6470.02

3.1770.06
2.9870.07
2.7870.07

50
51
53

45
45
40

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

(A)

(B)

(C)

(D)

4129

Fig. 6. SEM micrographs of several MAbTs ground in ethanol after setting for 24 h with a 2.5% Na2HPO4 solution: (A) 1 h, (B) 2 h, (C) 24 h and (D)
1 h at a higher magnication.

signicant increase in the reactivity of the materials

compared to those made by non-milled TTCP. The
mechanical activation effect has not previously been
described in the literature for b-TCP. It was conrmed
that this effect was not b-TCP source specic since
commercially available b-TCP ground for 4 h also
formed a setting cement with sodium phosphate
solution.
The formation of amorphous calcium phosphates
during milling led to a strong increase in the solubility of
the materials and therefore a higher supersaturation of
the cement liquid with regard to calcium decient HA.
Besides an increase of the thermodynamic solubility
(which should be independent of the particle size), the
rate of dissolution (kinetic solubility) correlated with
prolonged milling time. This was not only an effect of
smaller particle size because the b-TCP milled for 24 h
was similar to the 4 h milled sample with regard to
particle size, but had a 1.3 fold higher solubility. This
may explain why the setting reaction of b-TCP was
accelerated by prolonged milling.
It was hypothesised that most of the activated
(amorphous) fraction within a material had reacted
during setting, while the crystalline fraction remained
unreacted; setting experiments on thermal recrystallized
samples of milled b-TCP (2 h, 1050 C) were performed
and demonstrated a loss of reactivity. When these
recrystallised powders were combined with sodium
phosphate solution they no longer set; particle size, d50
of the 24 h ground sample was 2.7 mm before and
4.06 mm after recrystallisation. This indicated that the

observed reactivity of MAbT was a result of a crystalline

to amorphous phase transformation and not an effect of
smaller particle sizes.
The mechanical activation of b-TCP led to materials
that could be used to form a cement with setting
and mechanical properties demanded in clinical use.
The setting times with 2.5% Na2HPO4-solution as liquid
phase are in the range between 5 and 16 min and
might be adjustable by varying the sodium phosphate
content of the liquid. The initial setting reaction only
converts the amorphous content to calcium decient
HA, while the crystalline fraction mostly remains
unreacted. The amount of the amorphous phase
is directly linked to the mechanical behaviour of
the cements.
Fig. 7 shows the relationship between compressive
strength and the HA content of the cement at the time of
mechanical testing as determined by Rietveld analysis.
These data are taken from cements set for 24 h made
from MAbT ground for different time periods and for
cements aged for up to 28 d. It can be seen that a linear
relationship exists between strength and HA content
(R2 0:96), regardless of setting time. While it was
expected that increasing P:L ratio would have increased
mechanical strength [20], this appeared not to be the
case. This could have been because the range used was
too narrow to distinguish between test groups. If the
reaction of MAbT to CDHA does indeed proceed as in
Eq. (1) stoichiometric P:L ratio would be 17, however
difculty was obtained in producing workable pastes
above a P:L of 2.7.

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131

Compressive Strength (MPa)

4130

materials increased with grinding time such that they

could be used as HA cement forming reactants. Sodium
phosphate was found to accelerate the setting reaction
and clinically appropriate setting times could be
achieved. In the P:L ratio range investigated, mechanical
properties were found to be linearly related to hydroxyapatite content, and cements with compressive
strengths of over 50 MPa could be produced. Preliminary results indicate, that other calcium phosphates show
a similar activation behaviour like b-TCP, and this
processing method opens a new approach adjusting the
reactivity of CPC components.

60
Ageing Time 3-28days

50

Milling Time 1-24 hrs

40
30
20
y = 0.55x -0.87
R2 = 0.94

10
0
0

20

40
60
HA (wt%)

80

100

Fig. 7. Variation of compressive strength as a function of HA content

of set MAbT cements.

Porosity has been demonstrated to be an important

factor affecting the strength of cement systems [27];
strength is an inverse exponential function of porosity
[28,29]. In this system the prolonged grinding of MAbT
resulted in a decrease in porosity and increase in the
compressive strength of the cement. Although a linear
relationship was found to exist between ln compressive
strength and porosity, the limited number of data and
the simultaneous variation in phase composition limited
the value of this analysis.
Any water not consumed in the precipitation of HA
causes the formation of porosity in the cement, at a
powder to liquid ratio of 2.7 g/ml this porosity was
calculated to be B50%. Interestingly, the relative
porosity of cement produced with each powder was
shown to be in the region of 510% lower than this
value. This shortfall between calculated and theoretical
porosity may be a result of the compaction used during
the fabrication of the samples resulting in a reduction in
the porosity of the cement [30]. The reason for the
increased proportion of nanoscale pores in the 611 nm
range may have been caused by the different particle
diameters of b-TCP following grinding for 1 and 24 h,
which were shown to be B2.8 and B4.5 mm, respectively. In addition cement ground for 24 h was almost
fully reacted, thus pores formed were likely to be those
inherent in the microstructure. Cement made from
MAbT ground for 24 h appeared to be essentially free
of micro- and macro-pores which suggests that most likely
mechanism to further increase strength in this system is by
reduction in porosity level rather than pore size.

5. Conclusion
We report for the rst time the synthesis of an
amorphous tricalcium phosphate by means of highenergy ball milling of crystalline b-TCP in ethanol.
Furthermore, it was found that the solubility of these

References
[1] Kamerer DB, Friedman CD, Costantino PD, Snyderman CH,
Hirsch BF. Hydroxyapatite cement: a new method for achieving
watertight closure in transtemporal surgery. Am J Otol
1994;15(1):47.
[2] Kveton JF, Friedman CD, Piepmeier JM, Constantino PD.
Reconstruction of suboccipital craniectomy defects with hydroxyapatite cement: a preliminary report. Laryngoscope
1995;105(2):1569.
[3] Kveton JF, Friedman CD, Constantino PD. Indications for
hydroxyapatite cement reconstruction in lateral skull base
surgery. Am J Otol 1995;16(4):4659.
[4] Chow LC, Takagi S, Ishikawa K. Formation of hydroxyapatite in
cement systems. In: Brown WE, Constanz E, editors. Hydroxyapatite and related materials. Boca Raton, FL: CRC Press;
1994. p. 12737.
[5] Mirtchi AA, Lemaitre J, Terao N. Calcium phosphate cements:
study of the beta-tricalcium phosphatemonocalcium phosphate
system. Biomaterials 1989;10(7):47580.
[6] Mirtichi AA, Lemaitre J, Munting E. Calcium phosphate
cements: action of setting regulators on the properties of the
beta-tricalcium phosphatemonocalcium phosphate cements.
Biomaterials 1989;10(9):6348.
[7] Brown WE, Chow LC. A new calcium phosphate, water-setting
cement. In: Brown PW, editor. Cements research progress.
Westerville, OH: The American Ceramic Society, 1986. p. 35279.
[8] Chow LC, Markovic M, Takagi S. Calcium phosphate cements.
In: Struble LJ, editor. Cements research progress. Westerville,
OH: The American Ceramic Society, 1997. p. 21538.
[9] Chow LC. Development of self-setting calcium phosphate
cements. J Ceram Soc Jpn 1991;99:95464.
[10] Driessens FCM, Boltong MG, Planell JA, Bermudez O, Ginebra
MP, Fernandez E. A new apatitic calcium phosphate bone
cement: preliminary results. In: Ducheyne P, Christiansen D,
editors. Bioceramics, vol. 6. London, UK: Butterworth-Heinemann, 1993. p. 469-472.
[11] Ginebra MP, Fernandez E, Boltong MG, Driesens FCM, Planell
JA. Inuence of the particle size of the powder phase in the setting
and hardening behaviour of a calcium phosphate cement. In:
Sedel L, Rey C, editors. Bioceramics, vol. 10. New York: Elsevier
Science, 1997. p. 4814.
[12] Ginebra MP, Fernandez E, Driessens FCM, Boltong MG,
Muntasell J, Font J, Planell JA. The effects of temperature on
the behaviour of an apatitic calcium phosphate cement. J Mater
Sci: Mater Med 1995;6:85760.
[13] Ginebra M, Fernandez E, Boltong MG, Driessens FCM, Ginebra
J, De Maeyer EAP, Verbeeck RMH, Planell JA. Setting reaction
and hardening of an apatitic calcium phosphate cement. J Dent
Res 1997;76:90512.

ARTICLE IN PRESS
U. Gbureck et al. / Biomaterials 24 (2003) 41234131
[14] Sanin N, Takagi S, Chow LC, Matsuya S. Particle size effects on
pH and strength of calcium phosphate cement. IADR 1991,
Abstract No. 2411.
[15] Otsuka M, Matsuda Y, Suwa Y, Fox JL, Higuchi WI. Effect of
particle size of metastable calcium phosphates on mechanical
strength of a novel self-setting bioactive calcium phosphate
cement. J Biomed Mater Res 1995;29:2532.
[16] Lee DD, Rey C, Aiolova M, Toghi A. Methods and products
related to the physical conversion of reactive amorphous calcium
phosphate. US Patent No. 6117456, 1996.
[17] Lee DD, Rey C, Aiolova M. Synthesis of reactive amorphous
calcium phosphates. US Patent No. 5683461, 1995.
[18] Gaffet E, Harmelin M. Crystal-amorphous phase transition
induced by ball milling in silicon. J Less-Common Met
1990;157:20122.
[19] Weeber A W, Bakker H. Amorphisation by ball milling: a review.
Physica B 1988;153:93122.
[20] Chow LC, Hirayama S, Takagi S, Parry E. Diametral tensile
strength and compressive strength of a calcium phosphate cement:
effect of applied pressure. J Biomed Mater Res (Appl Biomater)
2000;53:5117.
[21] TOPAS Tutorial Quantitative Analysis, Users Manual, Bruker
AXS, Karlsruhe, 2001.
[22] ASTM-Standard C26699: Standard test method for time of
setting of hydraulic cement paste by Gilmore needles, ASTM
International 2002.

4131

[23] Elliott JC. Structure, chemistry of the apatites and other calcium
orthophosphates. Amsterdam, London, New York, Tokyo: Elsevier, 1994, p. 6.
[24] Boudeville P, Serraj S, Lleloup J M, Margerit J, Pauvert B, Terol
A. Physical properties and self-setting of calcium phosphate
cements from bis-dihydrogenophosphate monohydrate and calcium oxide. J Mater Sci: Mater Med 1999;10:99109.
[25] Serraj S, Boudeville P, Pauvert B, Terol A. Effect of dry
mechanical grinding of calcium phosphate mixtures. J Biomed
Mater Res 2001;55:56675.
[26] Matsuya Y, Matsuya S, Antonucci JM, Takagi S, Chow LC,
Akamine A. Effect of powder grinding on hydroxyapatite
formation in a polymeric calcium phosphate cement prepared
from tetracalcium phosphate and poly(methyl vinyl ethermaleic
acid). Biomaterials 1999;20:6917.
[27] Ishikawa K, Asaoka K. Estimation of ideal mechanical strength
and critical porosity of calcium phosphate cement. J Biomed
Mater Res 1995;29:153743.
[28] Ryshkewitch E. Compression strength of porous sintered alumina
and zirconia. J Am Ceram Soc 1953;36:658.
[29] Duckworth W. Discussion of the Ryshkewitch paper. J Am
Ceram Soc 1953;36:68.
[30] Barralet JE, Gaunt T, Wright AJ, Gibson IR, Knowles JC. Effect
of porosity reduction by compaction on compressive strength and
microstructure of calcium phosphate cement. J Biomed Mater Res
2002;63:19.