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Biomaterials 23 (2002) 41134121

Effect of CaF2 on densication and properties of hydroxyapatite


zirconia composites for biomedical applications
Hae-Won Kima, Yoon-Jung Noha, Young-Hag Koha, Hyoun-Ee Kima,*, Hyun-Man Kimb
b

a
School of Materials Science and Engineering, Seoul National University, Seoul 151-742, South Korea
Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, Seoul 110-749, South Korea

Received 12 December 2001; accepted 18 April 2002

Abstract
Hydroxyapatite (HA) composites with zirconia (ZrO2) up to 40 vol% were fabricated with the addition of CaF2. The sinterability
of the composites was found to be enhanced markedly by the addition of small amounts of CaF2 (o5 vol%). Decomposition of HA
to b-TCP was suppressed due to the substitution of F for OH, consequently forming uor-hydroxyapatite (FHA) solid solution.
This suppression of decomposition allowed the production of a fully dense body, which retained both high exural strength and
fracture toughness. The osteoblast-like cell (MG63) response to these F ion-containing composites displayed comparable cell
viability to pure-HA by in vitro proliferation test. r 2002 Elsevier Science Ltd. All rights reserved.
Keywords: HA; ZrO2; CaF2; Substitution; Densication; Strength; Toughness; Cell viability

1. Introduction
Because of its chemical composition and crystallographic structure similar to those of human hard
tissues, hydroxyapatite (HA) has been extensively
studied for use as bone and tooth implants [14].
However, as HA is intrinsically poor in mechanical
properties, bone replacement parts made from HA have
been used only in non-load-bearing areas such as the
ossicles in the middle ear [4,5]. Therefore, for full
utilization of bioactive HA-based implants, improvements in mechanical properties are necessary.
The most common approaches were the incorporation
of reinforcing phases, in the form of particles, platelets,
and whickers, of different ceramic oxides or/and metal
dispersions [611]. Among them, zirconia (ZrO2) has
been found to retain high mechanical strength and
toughness without degrading the biocompatibility of
HA when incorporated as a second phase [7,8,1215].
However, when using ZrO2 as a reinforcing phase for
HA, the decomposition temperature of HA to tricalcium
phosphate (TCP; a- or b-) and/or tetracalcium phosphate (TetCP) was reduced from the usual range of
B130014001C down to B100011501C [7,14]. The
*Corresponding author.
E-mail address: kimhe@snu.ac.kr (H.-E. Kim).

decomposition process itself renders a negative inuence


on the densication of HA due to the formation of
second phases and water vapor, and consequent
reduction in the mechanical properties. Moreover, the
newly formed second phases (TCP or TetCP) increase
the susceptibility to slow crack growth and the
biodegradability of the HA ceramics [16]. Hence, steps
must be taken to produce fully densied HAZrO2
composites without the decomposition of HA.
Until now, full densication of HAZrO2 composite
through pressureless sintering in air has been unsuccessful due to decomposition problems [7,17]. Therefore, in
most cases, hot-pressing (HP) [13,14] or hot-isostatic
pressing (HIP) [6,15] technique has been used. Sintering
in a humid atmosphere was also helpful in minimizing
the decomposition [12]. However, limitations were
experienced when applying pressure or introducing
water vapor extrinsically. Hence, alternatives should
be introduced to enhance the thermal stability of HA
intrinsically for densication of HAZrO2 composite.
It is known that uorapatite (FA) exhibits much
higher thermal stability than HA does [18,19]. Moreover, FA possesses a potential advantage over HA with
its higher chemical stability and aptitude to delay caries
process (caries-inhibiting) without the degradation of
biocompatibility [2022]. However, until now, only
limited works have been reported on the sintering

0142-9612/02/$ - see front matter r 2002 Elsevier Science Ltd. All rights reserved.
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H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

behavior and mechanical properties of FA [2326] and


FA-composites [27].
In this context, the current study was performed to
fabricate uor-hydroxyapatite (FHA) and ZrO2 composites through the incorporation of CaF2 as a source for
F. The effects of the added-CaF2 on sintering behavior
and mechanical properties were investigated. Moreover,
to assess biomedical applications, in vitro cell proliferation was performed to evaluate the cell viability of the
fabricated materials.

2. Materials and methods


2.1. Materials fabrication
As starting materials, high-purity HA (Alfa, Aesar
Co., Ward Hill, MA, USA) and 10, 20, 30 and 40 vol%
ZrO2 (3Y-TZP, Tosho Co., Tokyo, Japan) powders
were used to fabricate HAZrO2 composites, designated
as H10Z, H20Z, H30Z, and H40Z, respectively.
Different amounts of CaF2 (Sigma-Aldrich Co., Milwaukee, WI, USA) were added to each system up to 10
vol%. The powders were milled in ethanol for 24 h with
high-purity ZrO2 balls as media. After milling, the
mixture was dried in a rotary vacuum evaporator, and
passed through a 70-mesh screen. After drying at 801C
for 24 h, the powder mixtures were cold isostatic pressed
(CIP) at 300 MPa followed by sintering without pressure
for 1 h at various temperatures (90015001C) in air. The
heating and cooling rates were 101C/min and furnace
cooling, respectively.

for 15 s, the fracture strength was measured with the 4point exural conguration mentioned above.
2.3. Cell proliferation
Each specimen set (H20Z+5%CaF2, H40Z+
2.5%CaF2, and pure-HA for comparison) for cell test
was prepared in a disc shape with dimensions of
B 11  1 mm2 (diameter  thickness) after polishing to
1 mm and sterilization at 1211C for 20 min. The MG63
cell line was cultured in asks containing Dulbeccos
modied Eagles medium (DMEM, Life Technologies,
Inc., MD, USA) supplemented with 10% fetal bovine
serum (FBS, Life Technologies, Inc., MD, USA).
To measure the effect of each material on the growth
of the MG63 cells, all specimens and Thermanox cover
slips (NUNC, IL, USA) for the control were placed in
individual wells of a 24-well plate, and 1.5  104 cells/
cm2 were plated onto the discs, then cultured for up to 7
days in a humidied atmosphere of a 5% CO2 in air at
371C within an incubator. After detaching the living
cells with trypsin-EDTA solution, they were counted
using a hemocytometer (Superior Co., German). Each
set of tests was performed in triplicate, and the data was
normalized with respect to surface area. The shape of
cell was observed with SEM after xing with glutaraldehyde (2.5%) and dehydrating with graded ethanol
(70%, 90%, and 100%).

3. Results
3.1. Microstructure and densification behavior

2.2. Characterization and mechanical test


The apparent porosity of the sintered specimens was
measured by the Archimedes method, and their microstructures were evaluated by scanning electron microscopy (SEM) after polishing with diamond slurries down
to 1 mm. The composition of specimens was characterized by X-ray diffraction (XRD) patterns. To investigate
structural changes during sintering, Fourier-transform
infrared (FT-IR) spectroscopy was used with the KBr
disk as a standard.
Specimens for mechanical testing were machined into
bar shapes of dimensions 3  4  25 mm3 and ground
with a 600-grit diamond wheel. The tensile side of each
specimen was polished with diamond slurries, and
subsequently beveled to minimize machining aws.
The exural strength was determined at room temperature by a 4-point exural conguration with a crosshead speed of 0.5 mm/min, and with inner and outer
spans of 10 and 20 mm, respectively. The fracture
toughness of the specimens was determined by the
indentationstrength (I2S) method [28]. After indenting the polished surface at 98 N with a Vickers indenter

The typical microstructures of the H20Z composite


were observed with SEM after sintering at 13501C for
1 h, as shown in Figs. 1(a)(d). Without CaF2, little
densication occurred, as manifested by a large amount
of remaining pores (Fig. 1(a)). However, the addition of
1 vol% CaF2 reduced the pore size markedly even
though a rather large amount of pores was still found
(Fig. 1(b)). With the addition of 5 vol% CaF2, almost
fully dense body was obtained with only small residual
pores (Fig. 1(c)). Moreover, ne ZrO2 grains (white
area) were uniformly dispersed in the HA matrix (black
area). Further addition (10 vol%) of CaF2 resulted in
some large pores together with rather apparent large
grains (Fig. 1(d)).
The apparent porosities of H20Z composites containing different amounts of CaF2 after sintering at various
temperatures for 1 h are shown in Fig. 2. Without CaF2,
a relatively large percentage of pores (2030%)
remained at all sintering temperatures, even though
porosity started to decrease above 14001C. However, the
addition of CaF2 reduced porosity signicantly for all
sintering temperatures, and nearly full densication was

H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

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Fig. 1. SEM evolution of HA-20 vol% ZrO2 composites after sintering at 13501C for 1 h: (a) without, (b) with 1 vol%, (c) with 5 vol%, and (d) with
10 vol% of CaF2.

Fig. 2. Apparent porosities of HA-20 vol% ZrO2 composites as a


function of sintering temperatures with variations in CaF2 addition.

Fig. 3. Apparent porosities of various HAZrO2 composites as a


function of CaF2 addition after sintering at 13501C for 1 h.

obtained at high temperatures. As the amount of CaF2


increased, the temperature required for full densication
decreased steadily.
This improvement in densication with CaF2 addition
was also observed in the other HAZrO2 composites
after being sintered at 13501C for 1 h, as shown in Fig. 3.
The addition of small amounts of CaF2 decreased the
porosity and resulted in nearly full densication. These
effects reached a steady state with further addition of
CaF2, except for the case of H40Z composites in which
large amounts of CaF2 (5 vol%) were not effective on
densication.

3.2. Decomposition and FHA formation


Phase changes of the HAZrO2 composites after
sintering at 13501C for 1 h, either without or with the
addition of 5 vol% CaF2, were analyzed by XRD
patterns, as shown in Figs. 4 and 5, respectively.
Without CaF2, large amounts of b-TCP were found, at
the expense of HA, in all HAZrO2 systems even though
there were some differences in their intensity (Fig. 4); the
lesser the amount of ZrO2, the stronger the b-TCP
peaks. Moreover, CaZrO3 and/or cubic-ZrO2 were
detected together with the b-TCP. To the contrary,

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H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

Fig. 4. XRD patterns of HAZrO2 composites with no CaF2, after


sintering at 11501C for 1 h (H: HA, b: b-TCP, Z: ZrO2, CZ: CaZrO3).

Fig. 5. XRD patterns of HAZrO2 composites with 5 vol% CaF2,


after sintering at 11501C for 1 h; (H: HA, b: b-TCP, Z: ZrO2, CZ:
CaZrO3).

there was little decomposition to b-TCP with the


addition of 5 vol% CaF2 (Fig. 5). However, CaZrO3
and/or cubic-ZrO2 peaks were still observed even
without HA decomposition.
The degree of HA decomposition to b-TCP for the
composites after sintering at 13501C for 1 h was
quantied from XRD, by comparing the relative
intensity of the HA and b-TCP main peaks, as presented
in Fig. 6. Without CaF2, signicant amounts of b-TCP

Fig. 6. Degree of decomposition of HA to b-TCP in HAZrO2


composites after sintering at 13501C for 1 h as a function of addedCaF2.

were formed in all HAZrO2 systems because of


decomposition. However, sharp decreases in b-TCP
contents were found with the addition of 2.55 vol%
CaF2, reaching a steady-state value with further additions.
To evaluate the structure change during sintering with
different amounts of CaF2, FTIR spectroscopy was
used after sintering of H20Z composites at 11001C and
11501C, as shown in Figs. 7 and 8, respectively. Without
CaF2, the hydroxyl bond (OHO) absorption was
observed at 3570 cm1 stretching and 630 cm1 liberational mode after sintering at 11001C (Fig. 7(a)).
However, when CaF2 was added, another band was
found at 3540 cm1 besides the 3570 cm1 mode, and the
630 cm1 liberational mode disappeared, indicating the
formation of FO bond stretch at the expense of OHO
bond, due to substitution of F for OH (Figs. 7(b)
(d)), as noted by other researchers [29,30]. As the
sintering temperature increased from 11001C to 11501C,
in the composite without CaF2 the band 630 cm1
disappeared and the PO vibration modes were weakened and broadened (Fig. 8(a)), conrming the formation of TCP [30,31]. However, there was no signicant
difference with temperature in the composites containing CaF2 (Figs. 8(b)(d)).
3.3. Mechanical properties
The 4-point exural strengths of the HAZrO2
composites after sintering at 13501C for 1 h are shown
in Fig. 9. Without CaF2, the exural strength of each
composite was very low, having a value of B40 MPa,
except for H40Z which was B80 MPa. With the

H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

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Fig. 9. Flexural strength of HAZrO2 composites after sintering at


13501C for 1 h as a function of added CaF2.
Fig. 7. FTIR analysis of HA-20 vol% ZrO2 composites after
sintering at 11001C for 1 h: (a) without, (b) with 1 vol%, (c) with
2.5 vol%, and (d) with 5 vol% of CaF2.

Fig. 10. Fracture toughness of HAZrO2 composites after sintering at


13501C for 1 h as a function of added CaF2.

Fig. 8. FTIR analysis of HA-20 vol% ZrO2 composites after sintering at 11501C for 1 h: (a) without, (b) with 1 vol%, (c) with 2.5 vol%,
and (d) with 5 vol% of CaF2.

addition of CaF2, the exural strength continued to


increase, reaching the highest value of 100150 MPa
with 5 vol% CaF2. In the H40Z composite, the highest
strength retained was B180 MPa with the addition of
2.5 vol% CaF2, but further addition of CaF2 decreased
the value rather sharply.
Fig. 10 represents the fracture toughness of the HA
ZrO2 composites after sintering at 13501C for 1 h. The

behavior of fracture toughness was rather similar to that


of exural strength for all systems. With no CaF2,
fracture toughness values were in the range B0.7
1.1 MPa m1/2; whereas, with small additions of CaF2,
pronounced increases in fracture toughness were observed for all the cases. Especially in H40Z, the value
reached up to B2.3 MPa m1/2 with 2.5 vol% CaF2.
3.4. Cell proliferation
Figs. 11(a)(d) show the shape of the attached cells
cultured on Thermanox and HAZrO2 composite
containing CaF2 for 3 and 7 days. After culture for 3
days, the cell shapes appear rather differently between

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H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

Fig. 11. SEM of osteoblast-like cells proliferated in Thermanox and HAZrO2 composite containing CaF2, after culture for 3 and 7 days: (a)
Thermanox for 3 days, (b) H20Z with 5% CaF2 for 3 days, (c) Thermanox for 7 days, (d) H20Z with 5% CaF2 for 7 days.

Thermanox (Fig. 11(a)) and HAZrO2 composite


(Fig. 11(b)). The star-like cells were spread on Thermanox and some parts of the surface remained uncovered
with cells. Whilst on HAZrO2 composite, cells were
grown and spread to meet together without the free
surface of the sample, disabling to separate cell
boundaries. Such difference in morphologies is believed
to be from differences in cell density as well as surface
conditions. After culture for 7 days, however, similar
appearances of cells were observed (Figs. 11(c) and (d)),
forming thick multiple layers of cells.
After culture for 7 days, the numbers of proliferated
cells were much higher than those of cells after 3 days in
all the cases (Fig. 12). Moreover, larger numbers of cells
were proliferated on HAZrO2 composites than on
Thermanox, this difference being more pronounced
after proliferation for 7 days. There were no signicant
differences between pure-HA and HAZrO2 composites
for all the culture periods.

Fig. 12. Cell proliferation rates of Thermanox, HA, and HAZrO2


composites containing CaF2, after culture for up to 7 days.

4. Discussion

be noted by the following Eq. (1) [32]:

Our study was undertaken to fabricate dense HA


ZrO2 composites by pressureless sintering, having
excellent mechanical properties as well as cell viability.
The main obstacle in the densication of the HAZrO2
composites was the decomposition of HA. Hence, the
priori requisition for full densication of HAZrO2
composites is the suppression of decomposition process.
The decomposition of HA in the presence of ZrO2 can

Ca10 PO4 6 OH2 t-ZrO2 3Ca3 PO4 2


c-ZrO2 =CaZrO3 H2 O:

The products, b-TCP and c-ZrO2/CaZrO3 phase, were


observed by XRD analysis in all CaF2-free HAZrO2
composites (Fig. 4). Even though the CaZrO3 compound was not found in H30Z and H40Z, the ZrO2 peak
characteristics changed from tetragonal to cubic due to
the diffusion of Ca2+ ions from HA to ZrO2. (The

H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

tetragonality of ZrO2 is easily illustrated from the


peak split at around 2y 351:) This pronounced
decomposition was effectively suppressed with the
addition of a small quantity of CaF2 (Figs. 5 and 6).
The addition of CaF2 was aimed at forming FHA by
the partial substitution of F for OH, since it is
well known that FA retains higher thermal stability
than HA without dehydration and decomposition at
elevated temperatures [18,19,24]. The reactions occurring during sintering of HAZrO2 composites with the
addition of CaF2 can be illustrated by the following
Eqs. (2) and (3):
Ca10 PO4 6 OH2 xCaF2
Ca10 PO4 6 OH22x F2x xCaO xH2 O;
CaO t-ZrO2 c-ZrO2 =CaZrO3 :

2
3

The Eq. (2) denotes the substitution of F for OH and


the formation of FHA, with an additional CaO phase
remaining, and Eq. (3) conrms the subsequent reaction
of tetragonal-ZrO2 with CaO to form cubicZrO2 and/
or CaZrO3 compound. In the presence of F, the
substitution for OH, and further formation of FHA
has been reported [30]. Moreover FA forms a solid
solution with HA over a wide range to form FHA. In
the samples containing 5 vol% CaF2, the formation of
CaZrO3 as well as the disappearance of tetragonality (no
peak split in 2y351) in the ZrO2 peaks supports the F
substitution (Fig. 5). Therefore, the Ca in CaZrO3 or cZrO2 in the CaF2-added composites differs in their
origin from the CaF2-free composites, i.e., they came
from CaF2 instead of the decomposition of HA. Even
though complete substitution might not occur, considerable uptake of F is possible as a result of hightemperature reaction. The substitution of F was well
illustrated by FR-IR spectroscopy, manifesting formation of FHA (Figs. 7 and 8). The shift in stretching
mode of the hydrogen bond from 3570 to 3540 cm1, as
well as the disappearance of OH-liberational mode at
630 cm1 with increasing the CaF2 content indicates the
formation of FHA. Furthermore, the complete disappearance of 3570 cm1 stretching mode with 5 vol%
CaF2 denoted substantial uptake of F ions.
As the substitution of F is closely related to the
restraining of decomposition, the addition of an
appropriate amount of CaF2 should be considered
according to several factors. Above all, the relative
amount of HA to ZrO2 is crucial, i.e. as the amount of
ZrO2 increases, the F content required for effective
substitution for OH in HA decreases. However, partial
substitution of F for OH was found to be effective
enough to suppress decomposition in this study. For
example, with only 2.5 and 5 vol% addition of CaF2 to
H40Z and H20Z composites, respectively, complete
restraining of decomposition was possible, because the
saturation amounts of CaF2 for complete substitution

4119

for OH are 4.61 and 6.15 vol% in H40Z and H20Z
composites, respectively. Along with the relative amount
of HA to ZrO2, the contact area of the two powders
relating to powder morphology, size, and degree of
mixing is also important, as the decomposition occurs
mainly around the contact of the two powders. With due
allowance for the different characteristic of each HA
ZrO2 system, the appropriate addition of CaF2 was
effective in improving sinterability without decomposition.
For usage as dense implants and substitutes for
teeth and bone, these fabricated composites should
retain high-mechanical properties, such as strength
and toughness, considering that the main drawback
to the wider applications of HA-based bioceramics is
their weakness in strength and toughness. The increase
in densication achieved by restraining decomposition
was directly correlated with these two important
mechanical properties. The trends in both mechanical
values for all HAZrO2 systems were similar to those
for the porosity results (compare Figs. 9 and 10 with
Fig. 3). Moreover, the amount of CaF2 for the highest
mechanical value in each composite coincided with the
amount of CaF2 for full densication. Hence, it is
suggested that the enhancements in both mechanical
properties are resulted from the decrease in porosity. It
is well known from the DuchworthKnudsen model that
mechanical properties, such as strength, hardness,
elastic modulus, and toughness, in brittle materials are
inversely proporational to the exponent of porosity
[33,34].
Even though the addition of small amount of CaF2
was found to be effective in enhancing the mechanical
properties correlated with densication, further addition
was deleterious to the mechanical properties. This
weakening was most pronounced in H40Z composites
with 5 vol% CaF2, and was due to adverse effect of
excess CaF2, remaining without becoming involved in
the formation of FHA, even though such excess CaF2
was not found by XRD because the level was below the
detection limit in this study. The residual CaF2 is known
to form eutectic liquid with HA or TCP at sintering
temperatures [24,25]. Relatively coarsened grains and
pores with higher addition of CaF2 suggest the
possibility of eutectic liquid (Fig. 1(d)). However, with
small additions of CaF2 (2.55 vol%), it was possible to
obtain HAZrO2 composites that retained excellent
exural strength and fracture toughness. Especially in
the H40Z composite, the addition of 2.5 vol% CaF2
increased 4-point exural strength and fracture toughness to B180 MPa and B2.3 MPa m1/2, respectively,
which were considerable increases compared to those of
CaF2-free H40Z composite. This enhancement in
strength coupled with fracture toughness has the
potential for promising applications in load-bearing
biological systems.

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H.-W. Kim et al. / Biomaterials 23 (2002) 41134121

The human osteoblast-like cell (MG63) culture was


preformed to evaluate the cell viability of the fabricated
materials. The cell responses to the HAZrO2 composites were rather similar with those of pure-HA,
conrmed by the shape and number of proliferated
cells, and represented a comparable cell viability up to 7
days. Usually, it is known that the attachment and
spreading of cells, especially at the initial stage, are
much affected not only by chemical composition but
also by physical status of the test materials, such as
roughness, porosity, morphology, and surface energy
[35,36]. Even though each sample tested in this study
differed in those physical and chemical characteristics,
the porosity and roughness of all samples except
Thermanox were indeed conditioned identically, in
other words, fully densied and equally polished to
1 mm. Hence the proliferation data up to 7 days are
adequate in providing an understanding of the cell
viability of the HAZrO2 composites by their wellbehaved cellular responses, to a large extent regardless
of the surface conditions. Thus, the responses of
osteoblast-like cells to the fabricated HAZrO2-system
with CaF2 are regarded as comparable to those of HA
within the category of attachment, spreading, and
proliferation.

[8]

[9]

[10]

[11]
[12]
[13]

[14]

[15]

[16]

[17]
[18]

5. Concluding remarks
HAZrO2 composites were pressurelessly sintered
with small additions of CaF2. The substitution of F
for OH made it possible to form FHA, and thereby to
restrain the decomposition of HA to b-TCP. As a result,
dense bodies retaining high strength and toughness were
obtained. The in vitro response of osteoblast-like cells to
the composites showed comparable cell morphology and
proliferation rate to pure-HA.

[19]

[20]
[21]

[22]
[23]

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