Tubular hydroxyapatite scaffolds
F. C. Gomes de Sousa1 and J. R. G. Evans*1
Published by Maney Publishing (c) IOM Communications Ltd
30
Ordered tubular structures with open porosity were created by microextrusion freeforming of
tubular latticework. The extrudate was a suspension of fine hydroxyapatite powder in isopropyl
alcohol with a polyvinyl butyral binder. The extruder consisted of a stepper driven syringe fitted
with a miniature tube extrusion die. The lattices were sintered at 1250uC to produce a ceramic
which has potential as a bone scaffold that could accommodate growth promoters for slow
release.
Keywords: Hard tissue scaffold, Microextrusion, Solid freeforming, Tubular latticework
Introduction
Extrusion freeforming is a generic term for a class of
processes in which a three-dimensional object is created
from the patterns traced by a computer controlled
extruder nozzle. It has its origins in the coiled clay pots
of antiquity1 but has acquired a range of proprietary
names originating from different laboratories. Fused
deposition modelling (FDM) is a process for prototyp-
ing using thermoplastic polymers, typically acrylonitrile
butadiene styrene,2 while fused deposition of ceramics
(FDC) has been used to prepare a wide range of
functional ceramic devices by a similar extrusion free-
forming method but using polymeric suspensions of
powder.3–5 In both these processes, a strand of the
building material is fed into a heated die such that the
solid strand acts as a piston to eject the melt. Multiphase
jet solidification6 uses a more conventional melt extru-
sion arrangement. Thermosetting materials can also be
subjected to extrusion freeforming7 providing state
change by crosslinking or polymerisation rather than
polymer crystallisation or cooling below the glass
transition. Volatilisation of water8 or a solvent9 can
also be used to effect state change in microextrusion
freeforming.
Applications for extrusion freeforming are expanding
rapidly. When a monolithic component is created by
these methods, as with all solid freeforming processes
there is generally evidence of the layer by layer
deposition method in the form of surface ripples,
sometimes known as stair stepping. In the case of open
structures based on latticework, this effect is unim-
portant. Thus direct9 and indirect10 methods have been
used to make organised microstructures for hard tissue
scaffolds.
In bone tissue engineering, biomaterials such as the
calcium phosphates provide scaffolds which foster
osteogenic cells to form bone.11 Previous materials used
for this purpose include ostrich or hen’s eggshell, marine
coral, bovine cortical bone and plaster of Paris.9
1
Department of Materials, Queen Mary, University of London, Mile End
Road, London E1 4NS, UK
*Corresponding author, email j.r.g.evans@qmul.ac.uk
Advances in Applied Ceramics 2005 VOL 104 NO
Hydroxyapatite foams12,13 allow the chemical composi-
tion to be controlled but not the microstructure. Solid
freeforming allows composition, microstructure and
macroscopic shape to be controlled by computer. Thus
three-dimensional honeycomb ceramic structures have
been made by FDM.14 The scaffold can be made highly
porous with an interconnected pore network for cell
growth.15
Several branches of medicine make use of biodegrad-
able materials including traumatology, orthopaedic
surgery, maxillofacial surgery and dentistry. An ideal
scaffold should withstand initial hyperplasia, biodegra-
dation and local thrombosis. It should not induce
inflammatory or immunological responses and even
show some degree of resistance.16,17 In the case of hard
tissues, the phase composition of calcium phosphates
can be adjusted to allow bone resorption.18
Therapeutic agents such as proteins including growth
hormones, bone morphogenetic proteins and antibiotics
can be incorporated into bone substitute bioceramics.19
Of interest therefore is the application of scaffolds built
from continuous ceramic tube which might be filled with
a gel containing such growth promoters. Sintering to
allow controlled continuous microporosity would allow
slow release. Indeed there is growing evidence that bone
scaffolds should generally provide either microporosity
or high specific surface area (the causative factor is not
firmly identified) in order to function best as a growth
promoter for osteoblasts.20
Outside the medical arena there are new and exciting
applications for microextrusion freeforming, most nota-
bly in microfluidics, which demands heat exchangers,
mixers, reactors and separators all with channels or
features at the submillimetre scale.21 Indirect extrusion
freeforming has been used to make motionless mixers on
a submillimetre scale.22 The review of microtubes of a
wide range of dimensions by Hoffman et al.,23 with its
superb images, highlights many other potential uses.
The present paper deals with direct extrusion free-
forming of microtube lattice structures. Microtubes with
diameters of the order of tens to hundreds of micro-
metres are finding increasing application in fields
including microelectromechanical systems (MEMS),
optics, catalysis, filtering, microfluidics, electronics and
ß 2005 Institute of Materials, Minerals and Mining
Published by Maney on behalf of the Institute
Received 28 June 2004; accepted 10 August 2004
1 DOI 10.1179/174367605225011025

medical technology.24 In Colombo et al.,24 the tubes are
made from a preceramic polymer by coextrusion with
and without a fugitive internal core. As discussed below,
the role of the core becomes increasingly important as
the internal diameter decreases in the quest for further
miniaturisation.
Experimental procedure
The details of materials together with their sources are
given in Table 1. The powder used was a fine hydro-
xyapatite as confirmed by X-ray diffraction (XRD).
Scanning electron microscopy (SEM) showed that the
powder was made up of both large and small
agglomerates with ultimate particles in the ,100 nm
diameter region (Fig. 1). Some powder was milled in
isopropyl alcohol using a high energy bead mill
(Dyno-mill KDL-A, Glen Creston, London, UK)
charged with 0.5 mm diameter zirconia media. Other
suspensions were prepared from powder calcined by
heating to 1000uC for 1 h at a rate of 3 K min21 rise and
fall.
Published by Maney Publishing (c) IOM Communications Ltd
Suspensions of the ceramic powder were prepared in
propan-2-ol with polyethylene glycol and polyvinyl
butyral in different ratios and dried to form pastes of
various compositions. The compositions based on the
dried system are given in Table 2. The volume fraction
of powder based on the solvent free system was chosen
conservatively to inhibit shrinkage cracking which is
associated with drying shrinkage and the development
of high modulus typical of polymer depleted systems.
In all cases, the weighed amounts of polymer were
added to sufficient solvent to allow them to dissolve and
the mixture warmed on a hotplate with constant stirring
to achieve complete solution. Powder was added and the
suspension was mechanically stirred, and then dispersed
with an ultrasonic probe (U200 S, IKA-werke, Staufen,
Germany). Samples of the fluid suspensions were
allowed to thicken in an oven at 60uC for 1 h with
intermittent stirring at 5–10 min intervals to allow the
development of an extrudable paste.
Extrusion was carried out over a three axis table
(Parker Hannifin, Offenburg, Germany) driven by a
four channel motion controller (Compumotor 6K4,
Micromech, Braintree, UK). The extrusion driver shown
mounted vertically over the centre of the three axis
table in Fig. 2 was a microstepper (50 000 steps per
revolution in continuous mode) (PS 6410, ACP&D,
Table 1 Details and sources of materials
Material Grade
Hydroxyapatite powder (HA) GPR
Polyvinylbutyral (PVB) BN 18
Polyethylene glycol (PEG) 6000 g mol21
20 000, melting range 60–65uC
Propan-2-ol GPR
Table 2 Compositions of HA suspensions used for microextrusion: compositions based on dried suspension
Suspension Preparation HA, wt-%
1 Milling 77.02
2 Ultrasonic 77.83
3 Ultrasonic 73.74
4 Ultrasonic 77.02
Gomes de Sousa and Evans Tubular hydroxyapatite scaffolds
1 Scanning electron micrograph of hydroxyapatite powder
Ashton-under-Lyme, UK) fitted with a low backlash
64 : 1 axially configured reduction gearbox driving a
1 mm pitch, 8 mm diameter ball screw (Automotion
International, Oldham, UK). This arrangement could
produce linear speeds down to 2 nm s21. A strain
gauged load cell (PB-GP, Flintec, Redditch, UK) was
fitted between the ball screw and the syringe both to
measure nominal extrusion load directly and to provide
an overload alarm for safety reasons.
Shortened and polished hypodermic needles were used
for extrusion of the ceramic pastes. The syringes were
1.0 mL Luer-lock (Microliter Gastight, Hamilton
Bonaduz AG, Switzerland). A range of nozzle diameters
were used in preliminary experiments for solid cylind-
rical extrusion (510, 410, 330, 190 and 100 mm). A
combination of two nozzles was used to produce tube
dies in the arrangement illustrated in Fig. 3. Two such
dies were used, (a) providing a nominal outside diameter
of 510 mm and inside diameter of 100 mm, (b) providing
an outside diameter of 600 mm and inside diameter of
300 mm. The working extrusion distance was 2–3 mm
between the tip of the nozzle and the deposition table.
Production of the lattice structures involved simulta-
neous action of the stepper motor extruder drive, which
applied pressure to the syringe contents, and the motion
planner profile, which moved the table. The program
ran continuously depositing layer by layer until suffi-
cient height was developed. The extruded structures
were deposited onto coarse alumina in shallow crucibles
and allowed to dry in air. The 0–90u lattice structures
Supplier Density, kg m23
Merck KgaA, 64271 Darmstadt, Germany 3160
Wacker Chemicals, Surrey, UK 1100
BDH Laboratory Supplies, Poole, UK 1210
BDH Laboratory Supplies, Poole, UK 1210
BDH Laboratory Supplies, Poole, UK 786
PVB, wt-% PEG, wt-% Ceramic, vol.-%
11.49 11.49 55
22.17 … 55
19.70 6.57 50
11.49 11.49 55
Advances in Applied Ceramics 2005 VOL 104 NO 1 31
 Gomes de Sousa and Evans Tubular hydroxyapatite scaffolds
Published by Maney Publishing (c) IOM Communications Ltd
2 Experimental arrangement showing extruder drive train
assembled vertically over three axis table
were 10610, 15615 and 25625 mm in the x–y plane
with 10 stacked layers (five in the x direction and five
orthogonally in the y direction).
The lattices were pyrolysed to 300uC in flowing air
with a heating rate of 5 K h21. This removed sufficient
organic phase to allow subsequent sintering in air for 5 h
at 1250uC using a heating rate of 5 K min21 rise and
furnace cooling. The sintered structures were examined
by scanning electron microscopy to reveal the surface
quality, core profile and extent of sintering.
3 Schematic diagram of tube microextrusion die
32 Advances in Applied Ceramics 2005 VOL 104 NO
4 Sintered 0–90u hydroxyapatite lattice
Results and discussion
Hydroxyapatite powders sometimes present processing
problems associated with poor stability of dispersion or
rheology. Fine powders such as this tend to be
agglomerated as well as showing significant solubility
in aqueous solvents compared with most oxide ceramics.
Even though the suspensions were diluted considerably
with propan-2-ol for bead milling, the milling treatment
caused a noticeable thickening of the suspension which
became gel-like after three passes. Pastes formed from
the milled powder could not be extruded easily even with
nozzle (b). They required high pressures, produced
irregular filaments both in thickness and shape, lacked
continuous internal cores and curled up on exit from the
nozzle. No lattices were produced from milled powder.
Subsequent work relied on the calcined powder and the
mixing method was ultrasonic dispersion (compositions
2–4).
Polyvinylbutyral, selected because of its excellent
adhesion properties, was used without success in
composition 2 without a lower molecular mass polymer.
Extrusions with hollow cores were produced using
nozzle (a) but tended to curl up near the die orifice
and to have striations, leading to longitudinal tears. No
lattices were produced with this composition.
In composition 3 the ceramic volume fraction was
reduced from 55 to 50%, and 25% polyethylene glycol
was added to the PVB. Before drying, this suspension
was not well stabilised and began to settle within the first
600 s. It needed constant mixing until thick enough for
extrusion. Despite poor colloidal stability, the paste
extruded well and the microextrusion apparatus could
be left running unattended to produce scaffolds of
chosen dimensions (Fig. 4). The PEG is not fully soluble
at ambient temperature, forming a paste that can be
used as a porosifier to enhance microporosity.
Such latticework had strong welds as evidenced by the
tendency of the lattice to fracture preferentially away
from the welds when manually compressed. Figure 4
shows a 0–90u tubular lattice made with die (a) and
composition 4. The filament extruded, deformed and
welded successfully as described previously for solid
strand filaments.9,25 However fracture of sintered fila-
ments showed that with die (a) the sintered filaments did
not have a continuous core. In fact this illustrates the
1

5 Fractured lattice exposing tubular filaments
main problem in the approach taken to this work and is
discussed in more detail below.
The die construction demands the smallest possible
aspect ratio for the core in order to maintain centrality.
Published by Maney Publishing (c) IOM Communications Ltd
With die (a) having 100 mm diameter wire, this presented
problems and the filament core was not consistently
central. The use of ‘spider’ supports was avoided
because of the likelihood of producing tubes with
weakened seams along the weld in crowded ceramic
suspensions. Die (b) was preferred because the inner
nozzle kept its central position better than die (a).
When using the larger die (b), a slow extrusion rate
was used to reduce curling up on exit and allow straight
deposition onto the moving table. When composition 4
was used with die (b) at a rate of 80–110 mm min21,
continuous tubular core was obtained within the lattice
structure and sintered filaments broken at random
showed a core 50–70 mm in diameter as illustrated in
Fig. 5, although some filaments showed inner diameters
of 30 mm, much smaller than the design of the die. Thus
a combination of composition 4 and die (b) successfully
gave tubular scaffolds and springs of adequate strength
for subsequent handling.
Tubular microsprings were also extruded by winding
onto a rotating mandrel. An example is shown in Fig. 6.
Microscopy of the polished section indicates continuity
of the hollow core as shown in Fig. 7. At a higher
magnification (Fig. 8) the microstructure of the sintered
hydroxyapatite and the inner surface of the core are
seen. Sintering at 1250uC does not produce full density
but it has been argued that some microporosity
6 Tubular microspring wound from composition 4
Gomes de Sousa and Evans Tubular hydroxyapatite scaffolds
7 Polished section of tubular spring extrusion showing inter-
nal continuity: 50–100 mm inner diameter after sintering
enhances the osteoinductive effect.20 If the tubes were
to be used for slow release of bone morphogenetic
proteins, continuous porosity would be required.
This method of making extruded microtubes is based
on the miniaturisation of macroscopic extrusion pro-
cesses for tubes using a core die which can be applied to
most classes of material. This work serves as a good
example of the problems that can occur in the
miniaturisation of processing operations. The ratio of
inner to outer diameter of the microtubes was always
less than the corresponding ratio of the die. For die (b)
(ri/r050.5), the ratio was 0.35¡0.09 after sintering.
Even before sintering takes place, the open inner core
is of sufficiently low diameter for viscous flow effects to
occur driven by the surface tension of the wet suspension
and opposed by its viscosity. The principal radii of
curvature for the inner core are ri and ‘, so that a
negative pressure given by c/ri is present in the core and
is equivalent to an external pressure acting on the tube26
of about 200 Pa. Closure of the inner core, or cylindrical
pore, can be opposed by using a more viscous
suspension, for example by employing less solvent and
applying higher extrusion pressure. However a further
requirement in the production of latticework is that
weldments should form between the extrudate and the
previous layers. This junction, in the case of 0–90u layup,
is a circle whose radius should increase with time to
produce a strong weldment under the influence of the
same driving force that tends to close the pore. The
8 Detail of inner core of filament
Advances in Applied Ceramics 2005 VOL 104 NO 1 33
 Gomes de Sousa and Evans Tubular hydroxyapatite scaffolds
equation for the growth of the area A of a neck in the
early stages for the similar geometry of a circular neck
between two spheres of viscous fluid was given by
Frenkel27 as
3 r0 c
A~ t 3. S. Rangarajan, G. Qi, N. Venkataraman, A. Safari and
2 g
where r0 is the outer radius, g is viscosity, c is surface
tension and t time. Thus for a microextrusion process
for tubular latticework, closure of a fine inner core is
subject to the same rate effects as welding between
filaments. As the process is further miniaturised, the
radii of curvature no longer allow the structure to be
treated as macroscopic. These are indeed ‘sintering
effects’ and they intrude at a stage long before ceramic
sintering begins. It is well known that sintering of
polymers obeys the Frenkel equation.28 The demands of
an open continuous core conflict with those for weld
formation and the best solution is likely to be the use of
a fugitive coextruded inner core as used by Colombo
et al.24 for the extrusion of ceramic microtubes from
preceramic polymers. Comprised of a fugitive powder
Published by Maney Publishing (c) IOM Communications Ltd
such as a carbon or graphite, this would ensure
continuity of the core while not interfering with weld
formation and is preferable to the use of an unfilled
polymer core which might liberate large volumes of
degradation product during pyrolysis.
Conclusions
Tubular lattice scaffolds and microsprings were success-
fully prepared from crowded ceramic suspensions of
hydroxyapatite by microextrusion solid freeforming with
a miniature tube die. The experiments highlight conflicting
demands placed on the suspension. Before drying there
should be enough flow to form welds between filaments
but insufficient flow to cause collapse of the internal core.
The former process is analogous to neck growth between
particles in sintering by vitrification while the latter is
similar to the sintering of a closed pore. In both cases, the
rate is proportional to the surface energy and inversely
proportional to the viscosity. It follows that reliable mass
production of microtubular lattices relies on coextrusion
with a fugitive core.
Acknowledgement
The authors are grateful to EPSRC for supporting this
work.
34 Advances in Applied Ceramics 2005 VOL 104 NO 1
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