1

Optimization of Bioceramic Manufacturing with

Structure of Scaffold
1

(A Literatures Study)
Adhi Setya Hutama1, Muhammad Kusumawan Herliansyah2

Department of Mechanical and Industrial Engineering, GadjahMada University, Yogyakarta, Indonesia

(Tel:+62-857-2900-2915; E-mail: adhisetyahutama@gmail.com)
2
Department of Mechanical and Industrial Engineering, GadjahMada University, Yogyakarta, Indonesia
(Tel: +62-819-0374-5579;E-mail: mkherliansyah@gadjahmada.edu)

Abstract. Tissue engineering is a developing biomedical technology that aims to help and accelerate the regeneration of the bone, by
planting scaffold in damage bone. The benefit of scaffold is to provide micro environment for the growth of new tissue, where that new
tissue will replace the old tissue that had been broken. This paper will review researches that related to the manufacture of scaffold
using 3D printing machine, and will discuss about the variables in scaffold manufacturing such as structure, flatness, and dimension of
the scaffold.
The expectation of this review is to obtain research gap, thus the new research topic in this area could be obtained. The benefit of this
research that associated with tissue engineering will develop the application of biomedical engineering

Keywords tissue engineering, Hydroxyapatite, scaffold, 3-D printing, optimization.

I. INTRODUCTION
Tissue engineering (TE), an important emerging topic in
biomedical engineering, has shown promise in creating
biological alternatives for harvested tissues, implants, and
prostheses [1]. Tissue engineering is a new concept for the
treatment of disease and injury. It involves the use of the
technologies of molecular and cell biology, combined with
those of advanced materials science and processing, in
order to produce tissue regeneration in situations where
evolution has determined that adult humans no longer have
innate powers of regeneration. The goal of tissue
engineering is to surpass the limitations of conventional
treatments based on organ transplantation and biomaterial
implantation [2].
Tissue Engineering Application
The field of tissue engineering is highly
multidisciplinary and draws on experts from clinical
medicine, mechanical engineering, materials science,
genetics, and related disciplines from both engineering and
the life sciences [1]. Bioceramic scaffold is one of
application from tissue engineering. These scaffolds
essentially act as a template for tissue formation and are
typically seeded with cells and occasionally growth factors,
or subjected to biophysical stimuli in the form of a
bioreactor; a device or system which applies different types
of mechanical or chemical stimuli to cells [3] An ideal
scaffold for bone engineering should fulfill a number of
criteria: (1) biocompatibility to enable cell attachment,
differentiation and proliferation, (2) osteoconduction and
osteoproduction (i.e. the material should induce strong bone
bonding), (3) biodegradability at a rate matching the rate of

new tissue formation, (4) mechanical competence, e.g. the

strength of the scaffolds should be sufficient to provide
mechanical stability in load bearing sites prior to
regeneration of new tissue, and (5) interconnected porous
structure with porosity 90% and pore size between 300 and
500 m for cell penetration, tissue in growth and
vascularisation [4].
Hydroxyapatite Scaffold
Designing tissue engineering scaffolds with the required
mechanical properties and favorable microstructure to
promote cell attachment, growth and new tissue formation
is one of the key hydroxyapatite challenges facing the tissue
engineering field. the scaffolds fabricated from pure
hydroxyapatite (HA) and composites of HA have received
considerable attention from researchers. However, the poor
mechanical strength is the major limitation of HA
application in the replacement of load-bearing bone defects.
The mechanical properties of scaffolds are strongly
influenced by the internal architecture at macro- and microlevels, therefore the improvement of scaffold strength with
tissue ingrowths by tailored porous structures becomes
essential in designing porous scaffolds for clinical use [5].
There are several requirements in the design of scaffolds
for tissue engineering. Many of these requirements are
complex and not yet fully understood. In addition to being
biocompatible both in bulk and degraded form, these
scaffolds should possess appropriate mechanical properties
to provide the correct stress environment for the neotissues.
Also, the scaffolds should be porous and permeable to
permit the ingress of cells and nutrients, and should exhibit

2
the appropriate surface structure and chemistry for cell
attachment.
The main advantage of inorganic scaffolds made of HA,
bioactive glass or other bioceramics is their high
biocompatibility. They suffer however from low
mechanical strength and high brittleness. One approach
being investigated to improve the mechanical properties of
these brittle scaffolds is to coat them with polymer layers,
in order to fill existing cracks in the bioceramic structure
with a polymer phase [6].
Researched have been conducted to measure the
synthesis and characterization of composites of
hydroxyapatite - chitosan - hidroxypropyl methylcellulose
(HPMC) as a paste injectable bone substitute (IBS) [7].
Composites made by mixing hydroxyapatite, chitosan and
HPMC. Characterization of IBS paste was conducted by
measuring of the water content, identification of functional
group with Fourier Transform Infra Red Spectrophotometer
(FTIR), and identification of sample morphology with
Scanning Electron Microscope Energy Dispersive
Spectrophotometer (SEM EDS). The result showed that the
water content of irradiated sample was higher than
unirradiated sample due to water radiolysis.
PU- Hydroxyapatite (PUHA) were investigated for
their ability to act as a scaffold for tissue engineered bone
[8]. Bioactive polymeric composite scaffolds were created
using 15 wt% Z3A1 in a 70/30 DMF/THF PU solution and
incorporating micro- or nano-sized HA particles in a ratio
of 3:1 respectively, whilst a 25 wt% Z9A1 PU solution was
doped in ratio of 5:1. Resulting composites were evaluated
by FTIR and physical properties by SEM. SEM images of
both electro spun PU scaffolds and PU HA composite
scaffolds showed differences in fibre morphology with
changes in solvent combinations and size of HA particles.
Inclusion of THF eliminated the presence of beads in
fibres that were present in scaffolds fabricated with 100%
DMF solvent, and resulted in fibres with a more uniform
morphology and thicker diameters. Mechanical testing
demonstrated that the Young's Modulus and yield strength
was lower at higher THF concentrations. Inclusion of both
sizes of HA particles in PUHA solutions rein forced the
scaffolds leading to higher mechanical properties, whilst
FTIR characterization confirmed the presence of HA in all
composite scaffolds.
Rapid Prototyping 3D Printing.
Rapid technology at tissue engineering is the key to
produce scaffolds with customised external shape and
predefined and reproducible internal morphology, which
not only can control pore size, porosity an pore distribution,
but can also make structures to increase the mass transport
of oxygen and nutrients throughout the scaffold. 3D
printing is a suitable technique to create custom implants
based on medical data sets. 3D printing allows to fabricate
scaffolds based on Hydroxyapatite with complex internal
structures and high resolution. 3D printing requires a 3D
dataset for the fabrication process. These data can originate
from medical imaging sources or CAD programs. Since 3D
printing generates physical models layerwise, the 3D
dataset has to be converted into 2D data by a special slice

algorithm. Afterwards, the 3D printer uses these 2D data to

create a physical model, which is a 1:1 copy of the
computer model [9].
Solid Freeform Fabrication in Tissue Engineering
It is appreciated that computer control of complex
internal features of scaffolds, such as pore size, porosity,
pore distribution and an artificial vascular system, offered
by SFF technologies is a great advantage to the tissue
engineer. An artificial vascular system is defined herein as
any structures contained within the scaffold that supply and
maintain an adequate mass transport of oxygen and
nutrients to the cells, and removal of waste metabolites
from the cells, throughout the whole scaffold.
Aquous-Based Extruction Fabrication
This system of Aquous-Based Extruction Fabrication
machine, developed by researchers at the University of
Freiburg, involves a moving extrude r head (x-, y- and zaxis control) and uses compressed air to force out a liquid
or paste like plotting medium. The extruder head can be
heated to the required temperature. The medium solidifies
when it comes in contact with the substrate or previous
layer [10]. Figure 1 shows this system.

Figure 1. Schematic diagram of the 3D Bioplotter system.

Aqueous based extrusion fabrication (ABEF) of ceramics is
a Solid Freeform Fabrication (SFF) process that deposits
ceramic paste layer by layer through extrusion [. The
process has been previously introduced, and details
regarding the build material and equipment can be found
[4,11,12]. The material deposition device previously
developed gave good results for continuous material
deposition. The ability to start and stop the material
extrusion on demand was not yet developed in our previous
work. With the need to be able to fabricate more complex
geometries, different extrusion processes were surveyed for
the process of starting/stopping material deposition on
demand. This process uses air pressure to extrude material
for deposition and uses one-way control valves for starting
and stopping of the extrusion process. These retraction
processes can be applied to the ABEF system by retreating
the ram extruder from touching the material reservoir

3
plunger. This would in theory reduce the applied pressure,
thereby stopping material extrusion.
The material from ABEF machine deposition tests are
conducted, where the ram extruder retreating velocity is
varied in order to develop a technique that can be used for
starting/stopping the extrusion process on demand [13]. A
new extrusion mechanism is designed to improve process
capabilities. Parts are fabricated with the use of
starting/stopping the extrusion on demand with emphasis
being placed on deposition of sharp corners and edges.

more accurate than interior due to less surface area for

drying.
The factors affecting the rapid prototyping of fine
lattices by extrusion freeforming of powder, notably
equipment accuracy, paste preparation, extrusion and postprocessing and their effects on filament deposition and the
defects that might be caused [14]. Extrusion freeforming,
which involves the direct assembly of filamentary lattices
by downloading a computer design file, can be used for
fabrication of hard tissue scaffolds [15]. The overall process
includes paste preparation, deposition of fine filaments by
an extruder and postprocessing, consisting of solidification,
debinding and sintering. Compared to fused deposition [12]
and gel extrusion [16], paste extrusion using a solvent is a
relatively simple technique without heating, cooling or
polymerization processes to contend with and can be easily
controlled [17].
II RESEARCH GAP

Fig.2 schematic of Masons ABEF machine

Experiments were conducted to test the feasibility of
stopping material deposition on demand by retreating the
ram extruder. The schematic of the original extrusion
mechanism utilizing a plastic syringe and hypodermic
needles is shown in Figure 2. Single lines were deposited at
table velocities of 25 mm/s and 30 mm/s with a desired ram
force of 308 N at a standoff distance of 150 m. These
process parameters yielded good deposition as determined
from previous part fabrication using the original extrusion
mechanism. Once the table velocity has reached a steady
state and traveled a fixed distance (5 mm), the ram was
retreated at a given velocity ranging 0-10 mm/s. After the
ram is retreated the amount of excess material deposited
was measured from the desired stopping location.
The result of experiment are A new extrusion
mechanism for the process of aqueous-based extrusion
fabrication of high solids loading ceramics on demand has
been designed and implemented, providing an extrusion
capability that cannot be done with the use of a plastic
syringe for extrusion. Deposition tests were conducted to
examine the relationship between ram retreating velocity
and excess material deposition. There is an exponential
decrease of excess material deposition with increasing ram
retreating velocity. The implementation of the new
extrusion mechanism allows for the extrusion to start and
stop as programmed. The ability to start and stop the
extrusion on demand allows for more complex 3D part
fabrication including sharp corners and features. Parts were
fabricated using the new material reservoir to demonstrate
the developed capability. Several features were measured
for dimensional accuracy compared to desired dimensions.
More shrinkage was present in the parallel deposition areas
than the perpendicular deposition areas due to a more even
area present for drying. The exterior part dimensions were

Research on the optimization of the HA scaffold was still

slightly. There are several ways to obtain optimization, such
as Taguchi Method, Surface Response Method, and Full
Factorial Design.
Process variability used Taguchi to find signal-to-noise
ratio permits the concurrent optimization of the process and
the reduction [11]. The ease of use, efficiency, and focus on
decreasing variability while optimizing the response more
than outweigh the disadvantage of the Taguchi method of
experimental design, as compared with the many other
experimental approaches currently in use.
The compression strength was doubled while maintaining
the appropriate porosity level and microstructure for
bioactivity. The mean value of the compression strength
obtained was 5.8 MPa with a density of 0.515 gm/cm3.
Three levels of porosity were identified namely, macro-,
meso-, and micro-porosity. The mean values of pore sizes
were 400, 100 and 6 m, respectively. By using the Taguchi
method in conjunction with a statistical experimental
design, the various steps of the scaffold production process
such as slurry preparation, coating process, drying,
calcining and sintering processes were optimized. The final
optimized process gave highly reproducible results. The
manner in which the Taguchi method was used to produce
synthetic bone scaffolds with desired properties is
described.
The optimization of the injection moulding process
parameters for optimum shrinkage performance of a plastic
tray which is made from polymer blends or poly blends
[18]. The concept of physically blending two existing
polymers is used to obtain new products or for problem
solving as suggested [19]. This study has purposely used a
blend of 75% polypropylene (PP) and 25% low density
polyethylene (LDPE) in order to obtain new product that
may contribute to make the recycling more economically
attractive and to improve the impact strength [20,21].
Response Surface Methodology (RSM) or method is a
response surface methodology consists of a group of
statistical techniques for building empirical models and
exploit models [22]. With a design experiment, the purpose

4
of this method is to optimize the response (variable output)
which is influenced by several dependent variable (input
variable) [23]. The reasons for selecting this method is
possibility of a shift in factor levels towards the optimum
response conditions. not just stop at the levels of factors
that have been experiment ordo determined at first, but also
can track the optimum point in the response outside area
experiment ordo level first. with Thus, the optimal point
obtained is not "Local optimum" but can reach or at least
approaching the position of "global optimum" of the
response variable.
Design experiments conducted to determine the point
optimum of the variables that affect production machine.
Free Variable used in the study include: type cup used, the
temperature of the first heater temperature heater II, where
the three factors are factors that can be controlled
(controllable) in the production. The dependent variable
(response) is the number product leak.

[12]

[13]

[14]

[15]

[16]

[17]

[18]

III. CONCLUSION
The purpose of this paper is to briefly provide an
overview research gap of the optimization scaffold
hydroxyapatite, and ABEF machine with Taguchi method
or Surface Response Method. thus the new research topic in
this area could be develop the application of biomedical
engineering
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