Porous Hydroxyapatite for Artificial Bone Applications

Abstract

Hydroxyapatite (HA) has been used clinically for many years. It has good biocompatibility in bone contact as its chemical composition is similar to that of bone material. Porous HA ceramics have found enormous use in biomedical applications including bone tissue regeneration, cell proliferation, and drug delivery. In bone tissue engineering it has been applied as filling material for bone defects and augmentation, artificial bone graft material, and prosthesis revision surgery. Its high surface area leads to excellent osteoconductivity and resorbability providing fast bone ingrowth. Porous HA can be produced by a number of methods including conversion of natural bones, ceramic foaming technique, polymeric sponge method, gel casting of foams, starch consolidation, microwave processing, slip casting, and electrophoretic deposition technique. Some of these methods have been combined to fabricate porous HA with improved properties. These combination methods have yielded some promising results. This paper discusses briefly fundamental aspects of porous HA for artificial bone applications as well as various techniques used to prepare porous HA. Some of our recent results on development of porous HA will be presented as well.

Full text

Science and Technology of Advanced Materials 8 (2007) 116–123
Porous hydroxyapatite for artificial bone applications
I. Sopyan
a,
, M. Mel
b
, S. Ramesh
c
, K.A. Khalid
d
a
Department of Manufacturing and Materials Engineering, Faculty of Engineering, International Islamic University Malaysia,
P.O. Box 10, 50728 Kuala Lumpur, Malaysia
b
Department of Biotechnology Engineering, Faculty of Engineering, International Islamic University Malaysia, P.O. Box 10, 50728 Kuala Lumpur, Malaysia
c
Ceramics Technology Laboratory, COE, University Tenaga National, Km-7, Jalan Kajang-Puchong, 43009 Kajang, Selangor, Malaysia
d
Faculty of Medicine, International Islamic University Malaysia, Jalan Istana, Bandar Indera Mahkota, 25200 Kuantan, Malaysia
Received 27 July 2006; received in revised form 17 November 2006; accepted 23 November 2006
Abstract
Hydroxyapatite (HA) has been used clinically for many years. It has good biocompatibility in bone contact as its chemical composition
is similar to that of bone material. Porous HA ceramics have found enormous use in biomedical applications including bone tissue
regeneration, cell proliferation, and drug delivery. In bone tissue engineering it has been applied as filling material for bone defects and
augmentation, artificial bone graft material, and prosthesis revision surgery. Its high surface area leads to excellent osteoconductivity and
resorbability providing fast bone ingrowth. Porous HA can be produced by a number of methods including conversion of natural bones,
ceramic foaming technique, polymeric sponge method, gel casting of foams, starch consolidation, microwave processing, slip casting, and
electrophoretic deposition technique. Some of these methods have been combined to fabricate porous HA with improved properties.
These combination methods have yielded some promising results. This paper discusses briefly fundamental aspects of porous HA for
artificial bone applications as well as various techniques used to prepare porous HA. Some of our recent results on development of
porous HA will be presented as well.
r2007 NIMS and Elsevier Ltd. All rights reserved.
Keywords: Porous hydroxyapatite; Preparation; Bone; Review
1. Introduction
A standard strategy applied when a bone loss occur is
bone grafts which include autografts, allografts, and
xenografts; each type has its advantages and disadvan-
tages. Autografts have the advantages of no adverse
immunological response and, even more importantly, it is
the best for inducing new bone formation in the host due to
its osteogenic capacity. However, this bone graft is usually
available in limited quantity. In addition, their availability
is qualitatively limited by the anatomy and physiological
conditions of the donor site; they have no mechanical
strength and shape which can precisely duplicate the bone
being replaced. They require additional surgery for
harvesting resulting in more pain for the patient. Besides
additional cost for longer time of surgery, there are other
disadvantages associated with the risk of donor site
morbidity like fracture, long lasting pain, nerve damage,
and possible infection.
Allografts, on the other hand, are available in consider-
able quantity, can be strong mechanically, and can
duplicate the deficit; unfortunately, however, they are
immunogenic and are not as osteoinductive as autograft
bone thus possibly leading to non-unions. The problems of
disease transmission like hepatitis and HIV are also well
documented. Their storage is expensive, altering mechan-
ical properties and biological response. Thus, with such
critical arguments on applications of naturally derived
bone grafts, development of artificial bone substitution
materials made from metals, ceramics, polymers, and
composites are of a great importance [1].
Hydroxyapatite (HA) ceramics has been widely applied
as bone substitutes. Together with b-tricalcium phosphate,
they have been for nearly three decades the most
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
Corresponding author. Tel.: +60 361964592; fax: +60 361964477.
E-mail addresses: sopyan@iiu.edu.my (I. Sopyan),ramesh@uniten.
edu.my (S. Ramesh).

extensively used substitution materials for artificial bone
grafts [2]. Their chemical composition close to the mineral
phase of bone is an origin of their excellent biocompat-
ibility to tissue bone. This meets the requirement of any
materials designed for bone repair and augmentation [3].
To this aim, a high degree of crystallinity and chemical
stability have been included among the desirable properties
of an ideal HA [4]. Although many problems concerning
infective risk, mechanical and biological stability, compat-
ibility, storage and costs still remain, HA materials have
been applied in orthopedics as block implants, granules or
coating, either dense or porous [5].
In recent years, particular attention has been paid to the
preparation of HA bioceramics with porous morphology.
Porous HA exhibits strong bonding to the bone; the pores
provide a mechanical interlock leading to a firm fixation of
the material. Bone tissue grows well into the pores,
increasing strength of the HA implant. It was realized that
dimension and morphology of pores are crucial factors for
an excellent osteointegraton [6–8]. Minimum pore size
required to enable ingrowth of the surrounding bone
together with blood supply, is about 100–150 mm for
macropores [9,10], and even at pores of as small as 50 mm
osteoconduction is still possible [11]. Some reports stated
that it should be 200–500 mm for colonization of osteoblast
in the pores, fibrovascular ingrowth and finally the
deposition of new bone [2,12]. Other important require-
ments for porous implants are interconnectivity of the
pores for the penetration of the osteoblast-like cells
inside the pores as well surface roughness for the
attachment of cells.
With larger pores strength of the implant decreases
significantly. Therefore, normally porous HA implants
cannot be heavy loaded and are used to fill only small bone
defects. The obtained physical characteristics in develop-
ment of porous ceramics for bone substitutes depend on
the porous volume of the biomaterials, as well as the mean
pore and interconnection sizes. A successful development
of porous bone substitutes with optimal properties requires
perfect control of these parameters.
2. Applications of porous HA
Porous HA have been applied for cell loading [13–17],
drug releasing agents [18–31], chromatography analysis
[17], and the most extensively for hard tissue scaffolds
[28,30,32–43]. Various cell products are therapeutically of
crucial significance including hormones, enzymes, vaccines,
and nucleic acids which could improve the technology of
the diagnosis and treatment of human diseases. Mamma-
lian cells can be grown and maintained in vitro, but are
generally anchorage-dependent, i.e., they need solid sub-
strate for growth. Most of animals cell used for the
production of viral vaccines, growth factors, receptors or
therapeutic proteins are anchorage-dependent.
Microcarrier culture technique is one of the methods
developed for cell cultivation. Owing to high surface area
for cells to adhere and grow, microcarrier culture offers a
practical high yield culture of anchorage-dependent cells
and thus it is possibly suitable for large-scale operations.
A variety of microcarriers, including those based on
dextran, polystyrene or cellulose, and collagen or gela-
tine-based macroporousbeads have been developed [16].
Ceramic microcarriers, on the other hand, introduces new
possibilities for the culture of animal cells. Ceramic
microcarrier is predicted to meet the special requirements
of a microcarrier technique due to good mechanical,
chemical and thermal resistances. The mean diameter of
microcarriers often lies in the range 130–200 mm, even
though a range as wide as 100–400 mm has been described
as suitable for growth [16].
In drug delivery systems, it has been recognized that a
system for the slow, local and continuous release of drugs
would be a decided advantage for the treatment of many
ailments. One of potential candidates for such controlled
drug delivery systems is porous ceramics; much attention
has been paid to porous HA. Owing to their physicochem-
ical and biological properties, porous HAs have been
proven as a potential candidate for bone drug delivery
system [41]. This type of drug delivery system, via use of a
bioactive matrix, can release a therapeutic agent in situ to
produce an anti-infection action associating the osteocon-
ductivity of materials. For example, chronic disease or
localized surgical intervention, relying on a sustained local
drug delivery, needs ceramic capsulae suitable to release
drugs at a controlled rate [31].
The flux of a substance across a porous layer is
connected to two main parameters: its solubility in the
physiological body fluids and the possible physical or
chemical bonds formed by its molecules with the walls of
the pores of the delivery device [25]. Several groups have
designed different types of porous calcium phosphates for
drug delivery accordingly. Palazzo et al. [21] tested their
porous HA device with a bimodal porosity degree (60%
and 40%) as controlled drug delivery devices for anti-
inflammatory drugs. Another device with a bimodal
porosity have been introduced for a controlled delivery of
an anti-phlogistic, hydrocortisone acetate [29]. An inter-
esting approach has been done by Komlev et al. [41] who
developed porous spherical HA granules and fluoroHA
granules applicable for bone drug delivery system. As well
known the incorporation of fluoride ions into the structure
of HA can stimulate bone cell proliferation and increase
new mineral deposition in cancellous bone. FluoroHA also
showed good integration in the bone tissue and much
longer resorption time than classic calcium phosphate [41].
On the other hand, for biomedical applications spherical
geometry is much preferable than irregular one to eliminate
non-desirable inflammation reactions from the body soft
tissues. Granules of diameter range from 50 to 200 mm with
open pores content of 43–62% were successfully prepared
(see Fig. 1). Bone drug delivery systems were also
developed using porous calcium phosphate ceramics
bonded with antibiotics through a biodegradable polymeric
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I. Sopyan et al. / Science and Technology of Advanced Materials 8 (2007) 116–123 117

matrices. Usage of biodegradable polymers is to obtain a
controlled release bone drug delivery device. Many types of
biodegradable polymers have been used for this purpose
including gelatin, albumin, and PLGA [44,45].
Porous HA has been extensively applied for artificial
bone substitutes. The primary purpose of tissue engineering
is repair, regeneration, and reconstruction of lost, damaged
or degenerative tissues. Although bone tissue itself shows
an excellent ability of bone regeneration, for big bony
defect or for such situations that bone healing process is
difficult bone grafts are required. At this point, it is very
crucial to match the osteoconductive properties of porous
ceramic scaffold in one side with the osteoinductive or
osteogenic properties of living bone cells in the other side.
Theoretically, a degradation rate of the implant similar to
the rate of tissue formation is expected. Therefore one of
important aspects in the development of bone and organ
substitute materials is the fabrication of supporting
matrices or scaffolds with an appropriate micro- and
macroscopic structural morphology including pore size,
pore interconnectivity, biocompatibility, osteoconductiv-
ity, mechanical strength, and biodegradability.
Results on histological analysis of osteoconduction in
vivo of porous HA showed that within six weeks after
implantation mature bone ingrowth was observed in the
whole parts of the porous HA [8], followed by an increase
in compressive strength of porous HA. Besides via
osteoconduction in vivo, bone tissue regeneration can be
conducted using carrier-scaffold system using biologically
active bone morphogenetic protein (BMP) as the carrier.
Embedding BMP on porous HA has enhanced bone
formation and reduced the amount of BMP used in
comparison with the cases in conventional studies [46].
Mesenchymal stem cells are also used as a source of bone-
producing cells [47]. Studies showed that initial bone
formation inside the pore areas can be seen after 2 weeks
implantation, and even at 8 weeks after implantation
extensive bone volume was detected in the center areas of
the implants. The combination of porous HA and
mesenchymal stem cells are a potential candidate for an
excellent bone graft substitute accordingly due to mechan-
ical properties and capability of inducing bone formation
[47,48].
3. Physical characteristics requirements of porous HA for
bone substitutes
Development of porous bone replacement materials are
addressed to mimic the micro- and macroporous architec-
ture of the mineral phase of living bone [2,25,39,49].
Macro- and microporous bioactive ceramics shows high
true surface area which facilitates appropriate contact
osteogenesis. This prevents interference of connective tissue
formation which will obstruct the long-term stability of the
implant. In the case of bioresorbable calcium phosphate
ceramics biodegradation rate can be even increased.
Physical characteristics of porous HA which include
porosity degree, pore-size distribution, pore morphology
and orientation, and pore interconnectivity influence bone
penetration in implants [2]. Pore characteristics are crucial
in bone engineering due to its close correlation to the
degree of bone ingrowth. Particularly porosity, pore-size
distribution, pore morphology and orientation, as well as
the degree of pore interconnectivity significantly affect
bone penetration in macropores of implants, thus mediat-
ing implant-tissue osseointegration. Pore interconnectivity
allows circulation and exchange of body fluids, ion
diffusion, nutritional supply, osteoblast cell penetration,
and vascularization. In this connection, closed pores do not
participate in physiological events due to lack of accessi-
bility by body fluids and cells [31].
Porous ceramic implants with a wide range of pore
size is necessary to meet all the functions involved in
osseointegration. Pores of 20–50 mm diameter may give a
favorable function for physiological liquid exchange [31],
while pores with a diameter 100–350 mm are suitable for
cell colonization and vascularization leading to bone
penetration into ceramics structure [50]. Thus, besides
conventional single mode porous HA, porous ceramics
with bimodal pore-size distribution [25,49] or even a
porosity gradient stimulating bimodal structure of natural
bone (cortical and cancellous) [39] have been developed.
The porosity-graded HA samples could be realized via
multiple and differentiated impregnations performed using
cellulosic sponges and HA slurries prepared with powders
of different crystallinity degree. Fig. 2 presents a SEM
micrograph showing the morphology of the porous HA
with a porosity gradient [39].
A dependence of bone ingrowth on the pore size has
been proved [51]. Some reports, however, stated that the
level of pore interconnectivity might be more critical than
the pore size [52]. For highly biodegradable porous
ceramics, interconnectivity degree is seemly more impor-
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Fig. 1. A photomicrograph of porous spherical hydroxyapatite granules
[41].
I. Sopyan et al. / Science and Technology of Advanced Materials 8 (2007) 116 –123118

tant than the pore size, but for non-biodegradable
materials interconnectivity and pore size were found to
be of equal significance. In vitro human osteoblast cells can
pervade pore interconnections if a minimal passage
diameter of 20 mm is provided, whereas the most favorable
size for cell penetration is above 40 mm. In vivo cell
penetration and chondroid tissue formation inside macro-
pores become possible at an interconnection size above
20 mm, and mineralized-bone formation occurs above
50 mm[2].
Apparent density and structural texture affect the
mechanical properties of porous ceramics. When pore
connectivity is made to be fixed, implants with larger
pore size have lower mechanical strength due to the
decreased density. Richart [53] proposed that the thickness
of inter-pore walls is responsible for the mechanical
strength of porous HAs. Flexural strength and Young’s
modulus of porous ceramics are correlated with the
total porosity of the ceramics via an exponential function
[51]. Mechanical failure may be initiated in macropore
interconnection.
Compressive strengths of porous human bones vary
between 2 and 12 MPa for cancellous bone and between
100 and 230 MPa for cortical bone [5]. The as-prepared
artificial porous HA have mechanical strength as low as
1.3–16 MPa [8,44,45], but bone ingrowth lead to the
enhanced compressive strength of porous implants. Even
for low density implants this observation is more obvious
due to faster bone growth. The compressive strength of
porous HA, for example, was reported to increase from 2
to 20 MPa after 3 months implantation [8]. Porous calcium
phosphates with lower density shows superior implants for
filling of osseous defects as a result of faster osteointegra-
tion rate resulting in in vivo mechanical performance. An
optimum balance between porosity and strength must be
achieved to assure that the implant can withstand the
applied forces in the course of operation and in the initial
stage at the implantation site.
4. Preparation methods
Great diversity of clinical reconstructive requirements
for the defects of the skeleton has led to development of
various methods to prepare porous ceramic implants. This
is to allow design and production of porous HA with
controlled porosity, good pore interconnectivity, mechan-
ical strength, and surface properties. Some of these
methods can be briefly explained as follows:
4.1. Formation of porous structure using pore-creating
volatile particles which burn away during sintering
Various kinds of pore making agents including
paraffin, naphthalene, carbon, starch, flour, hydrogen
peroxide, or synthetic polymers (for example polyvinyl
butyral) are admixed to HA powders or slurries.
After molding, the organics burn away from the molding
body during sintering. This approach allows direct control
over the pore characteristics since their fraction,
size, morphology, and distribution are controlled by
type, amount and properties of the added volatile phase.
Removal of pore-creating organics can either be con-
ducted by physical processes like vaporation and sublima-
tion or chemical reactions like combustion and
pyrolysis [2]. Obtained porous ceramics usually have closed
macropores with a varied pore size of 0.1–5000 mm
diameter [15].
4.2. Formation of porous structure via admixture of water-
soluble porogens with HA powders without sintering process
This method has been developed by Tadic et al. [54].It
consists of mixing salt crystals and water soluble polymers
as pore creating agents with calcium phosphate powders
followed by cold-isostatic pressing. Since porogens are
easily water soluble they can be removed without any heat
treatment. Pores are formed by the salt crystals and
channels between these pores are formed by the polymeric
fibers. The obtained porous HA showed good pore
interconnectivity with the pore diameters in the range of
250–400 mm as shown in Fig. 3.
4.3. Conversion of marine coral skeleton and natural bone
The three-dimensional skeletal structure of certain
marine corals mimics human cancellous bone and can be
used as a template for making any porous structures. In
this method, hydrothermal exchange reaction converts
calcium carbonate in the coral skeleton into HA in the
presence of phosphate ions. Di-ammonium hydrogen
phosphate is normally used as the source of phosphate
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Fig. 2. A SEM micrograph showing the morphology of polymeric sponge
method derived-porous hydroxyapatite with the porosity gradient [39].
I. Sopyan et al. / Science and Technology of Advanced Materials 8 (2007) 116–123 119

ions, as shown in the following:
10CaCO3þ6ðNH4Þ2HPO4þ2H2O!2Ca5ðPO4Þ3OH
þ6ðNH4Þ2CO3þ4H2CO3(1)
The resulting porous HA have macropores of around
200–500 mm diameter with good interconnectivity and
50–65% porosity, and these are enough facts for its
usefulness in obtaining artificial bone substitutes, however,
the limited amount of the marine coral is its obstacle.
Another factor should be considered is difficulty in
controlling porosity; diverse corraline species have differ-
ent skeleton porosities. For example, in Porites corals pore
diameters range from 190 to 230 mm mean in Goniopora
corals could range from 270 to 550 mm[55]. A commer-
cially available porous HA, Endobon
s
(Biomet UK Ltd),
is manufactured from natural cancellous bones by removal
of the organic component while preserving the trabecular
structure. With pore size of 100–1500 mm and excellent
interconnecting pore system (see Fig. 4), it is highly
osteoconductive [56].
4.4. Ceramic foaming technique
This technique involves foaming of ceramic suspensions
or swelling of ceramic green bodies via gas evaporating
chemical reactions from organic and inorganic sources.
Some foaming agents tested were hydrogen peroxide,
carbonate salt, and baking powder. They were added to
the HA slurries while stirring to let it foam, and then
subjected to polymerization followed by sintering [57].
Porous HA obtained has pore sizes of 30–600 mm[15].
Tamai et al developed a modified version of ceramics
foaming method they called ‘‘foam–gel’’ technique [58].
This technique involves a crosslinking polymerization step
that gelatinizes the foam-like HA slurry in a rapid manner,
thus promoting the formation of an interconnected porous
structure. The wall surface of the device obtained is very
smooth and HA particles are aligned closely to one another
and bound tightly. With average pore size 150 mm and
average interpore connections 40 mm, this device is favor-
able for interpore cell migration or tissue ingrowth. Gel
casting of foams can be applied to produce ceramic
scaffolds with high mechanical strength. The disadvantage
of this technique is that it typically results in a structure of
poorly interconnected pores and non-uniform pore size
distribution.
4.5. Polymeric sponge method
Another approach for fabricating porous ceramics is via
the replication of a polymeric sponge substrate to produce
reticulated open-celled porous ceramics. Porous ceramics
obtained from reticulated polymer substrates have a
number of distinct properties such as controllable pore
size and complex ceramic shapes suitable for different
applications [57,59]. The polymeric sponge method, as this
method named, is performed by impregnating porous
polymeric substrates (sponges) with HA slurry. Porous HA
prepared via the polymeric sponge method have shown
well- interconnected pores but poor mechanical strength
for load bearing applications. It was shown that the
polymeric sponge method results in a proper pore size
distribution, as osteoconduction requires. This is charac-
terized by the existence of micro/meso/macropores with
adequate degree of interconnection [39].
This method allows control on rheological properties of
the ceramics powder suspension by varying the character-
istics of starting powders. It has been shown that by
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Fig. 3. A SEM picture of porous HA after the removal of NaCl and PVA
as pore and pore connectivity-creating agents with water [54].
Fig. 4. A SEM micrograph of Endobon
s
[56].
I. Sopyan et al. / Science and Technology of Advanced Materials 8 (2007) 116 –123120

varying the characteristics of starting powders, that
powders of 20% and 80% crystallinity degree, rheological
properties of the ceramics powder suspension can be
controlled [60]. This allowed the possibility of preparing
HA ceramics with crystallinity and porosity gradients
mimicking the physicochemical features of cortical and
spongy bones. Use of well controlled HA suspension
enable to make HA ceramics with crystallinity and porosity
gradients mimicking the physicochemical features of
cortical and spongy bones as well as to fabricate porous
HA grafts for controlled drug delivery [39].
We have reported the preparation of HA porous bodies
(see Fig. 5) via polymeric sponge method; the samples
which were prepared using sol–gel method—derived HA
powders and commercial HA powders showed a consider-
able compressive strength ranging from 1.3 to 10.5 MPa
[44,45] for the increased apparent density from 1.27 to
2.01 g/cm
3
. This is higher than the 0.55–5 MPa compressive
strength obtained for the apparent densities of 0.0397–
0.783 g/cm
3
, as reported by Ramay et al. [61]. The porous
HA showed macropores of 400–600 mm diameters with
good pore interconnecting channels, as Fig. 6 shows. It was
also shown that homogeneity of slurry and heating rate
affected porosity and density of porous bodies, in turn
influencing the compressive strength [45]. More homo-
geneous slurries and faster heating rate gave porous bodies
with the increased compressive strength due to higher
apparent density and crystallinity [44,45].Fig. 7 shows
SEM images showing the difference in microporosity of
two porous HA samples obtained at different stirring
times. The sample of longer stirring time shows higher
density with larger grains. Our porous HA samples have
been tested for their biomedical performance as micro-
carriers for animal cell loading. Fig. 8 shows an initial stage
of attachment of Vero (African Green Monkey kidney) cell
on the surface of the porous HA. The Vero cell lines can be
regarded as a representative for attached mammalian cell
lines and have been utilized both in laboratorial and in
industrial scales for vaccine production, virus transfections,
and screening of Vero toxins. Possible attachment and
ARTICLE IN PRESS
Fig. 5. Porous hydroxyapatite bodies of various shapes produced via
polymeric sponge method using sol–gel derived HA powders.
Fig. 6. SEM images showing the morphology of macroporosity of porous
hydroxyapatite with 400–600 mm pore diameters and excellent pore
interconnectivity [45].
Fig. 7. SEM images showing the difference in microporosity of two porous hydroxyapatite samples obtained at different stirring times. The sample of
longer stirring time (a) shows higher density with larger grains than the counterpart (b) [45].
I. Sopyan et al. / Science and Technology of Advanced Materials 8 (2007) 116–123 121

subsequent growth of the Vero cell lines on the porous HA
microcarrier will be of clear indicative for its applicability
to anchorage-dependent mammalian cell culture. After
four days Vero cells have covered the whole surface of
porous HA microcarrier as shown in Fig. 9 [16].
Some of the above-mentioned methods have been
combined to produce porous HA with improved proper-
ties. Ramay and Zhang prepared HA porous scaffolds by
combining the gel-casting technique with polymer sponge
method. This novel technique resulted in porous HA with
improved mechanical strength and controllable pore
structure. The scaffolds prepared were found to have a
homogeneous microstructure, and an open, uniform and
interconnected porous structure with a pore size of
200–400 mm[60]. Sepulveda et al. [62,63] combined the
foaming and polymerization process, and this was followed
by sintering at 1250/1350 1C.
Porous HA can also be produced by a number of
miscellaneous methods including starch consolidation [64],
microwave processing [65], cold isostatic pressing [66] and
electrophoretic deposition technique [67]. The differences
in the methods used to produce porous HA can directly
affect the pore characteristics.
The starch consolidation method is based on the
swelling ability of starch when it is heated to 80 1Cin
the presence of water. This method can result in flexural
strengths of as low as 2 MPa for pore volume fractions
of 70% and as high as 15 MPa for pore volume fractions of
45%. The microwave processing technique has produced
porous HA with a porosity of up to 73%. The porosity of
the ceramic can be controlled by varying the morp-
hology of the starting materials, adjusting green density,
as well as altering the sintering time and temperature.
Cold isostatic pressing and sintering of HA powder
produces spherical, interconnected pores of 100–200 mm
in size. Eletrophoretic deposition (EPD) of submicron
HA powders produces uniform and crack-free bulk
porous HA scaffolds with good mechanical strength
and interconnected porosity with a wide range of pore
sizes.
5. Conclusions
The applications of porous HA in the biomedical field
are enormous; they have been used for hard tissue
scaffolds, cell loading, and drug releasing agents. In bone
tissue engineering, porous HA are used as filling material
for bone defects and augmentation, artificial bone graft
material, prosthesis revision surgery. Its high surface area
leads to excellent osteoconductivity and resorbability
favorable for fast bone ingrowth. A number of main
methods which have been used to prepare porous HA are
admixture of pore-creating organics which burn away
during sintering, ceramic foaming technique, conversion of
marine coral skeleton and natural bone, and polymeric
sponge method. Variation in preparation methods allowed
design and production of porous HA with controlled
porosity, good pore interconnectivity, mechanical strength,
and surface properties as demanded by clinical reconstruc-
tive requirements.
Acknowledgments
The authors are grateful to the financial supports
available from IIUM Research Center through a research
grant LT37. The authors gratefully acknowledge Brs.
Syamsul Kamal Arifin and Danial Mohammed by some
experimental works including SEM measurements. We
would like to thank Prof. Matthias Epple of Universita
¨t
Duisburg-Essen (Germany) who provided the SEM picture
as shown in Fig. 3.
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Fig. 9. A SEM image showing after a massive formation of cell layer after
fourth day: Vero cells have covered the whole surface of porous HA
microcarrier [16].
Fig. 8. A SEM image showing an initial stage of attachment of Vero
(African Green Monkey kidney) cell on the surface of the porous HA [16].
I. Sopyan et al. / Science and Technology of Advanced Materials 8 (2007) 116 –123122

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