Int J Adv Manuf Technol (2009) 40:116–127
DOI 10.1007/s00170-007-1308-1
ORIGINAL ARTICLE
Additive fabrication technologies applied to medicine
and health care: a review
J. Giannatsis & V. Dedoussis
Received: 26 April 2007 / Accepted: 6 November 2007 / Published online: 18 December 2007
# Springer-Verlag London Limited 2007
Abstract Additive fabrication (AF) and rapid prototyping
(RP) technologies are mostly associated with applications
in the product development and the design process as well
as with small batch manufacturing. Due to their relatively
high speed and flexibility, however, they have also been
employed in various non-manufacturing applications. A
field that attracts increasingly more attention by the
scientific community is related to the application of AF
technologies in medicine and health care. The associated
research is focused both on the development of specifically
modified or new methods and systems based on AF
principles, as well as on the applications of existing systems
assisting health care services. In this paper, representative
case studies and research efforts from the field of AF
medical applications are presented and discussed in detail.
The case studies included cover applications like the
fabrication of custom implants and scaffolds for rehabilita-
tion, models for pre-operating surgical planning, anatomical
models for the mechanical testing and investigation of
human bones or of new medical techniques, drug delivery
devices fabrication, as well as the development of new AF
techniques specifically designed for medical applications.
Keywords Additive fabrication . Rapid prototyping .
Rapid manufacturing . Biomodelling . Scaffold fabrication .
Medical applications
J. Giannatsis : V. Dedoussis (*)
Center for Product Development and Rapid Prototyping,
University of Piraeus,
80 Karaoli & Dimitriou str.,
18534 Piraeus, Greece
e-mail: vdedo@unipi.gr
J. Giannatsis
e-mail: ggian@unipi.gr
1 Introduction
Additive fabrication (AF) is a relatively new concept that
emerged during the last decade in order to describe a set of
new or under-development manufacturing methods, pro-
cesses and technologies that function through material
addition, in contrast to the established traditional cutting,
forming or casting methods. Rapid prototyping (RP)
technologies are the most widely applied and known
fabrication methods that are based on additive fabrication
principles. Some of the major RP technologies used
worldwide are stereolithography (SL), selective laser
sintering (SLS), fused deposition modelling (FDM), 3D
printing (3DP), multijet modelling (MJM) and laminated
object manufacturing (LOM). The main applications of RP
include the fabrication of various kinds of models and
prototypes for concept evaluation and presentation as well
as functional testing of new products early in the product
development process [1]. The continuous improvement of
RP systems accuracy and materials, expand gradually their
applications to other areas of the industrial sector like rapid
manufacturing (RM - the actual manufacturing of products
in small batches) and rapid tooling (RT - fabrication of
manufacturing tools and moulds).
What makes RP particularly appealing for all of the
above applications is the fact that compared to alternative
manufacturing technologies, like for instance CNC machin-
ing, RP systems can fabricate parts of almost any
geometrical complexity in relatively lower time and with
reduced cost and without significant requirements in
technical expertise. This kind of geometric flexibility,
which is mostly a consequence of their additive nature, is
the main reason that RP technologies are increasingly used
or tested in non-industrial applications like medical and
architectural modelling [2] or artistic creation [3]. The
Int J Adv Manuf Technol (2009) 40:116–127
medical branch in particular has attracted the attention of
many researchers and scientists since the first introduction
of RP technologies, and has been the topic of various EU
research programs (e.g., Phidias – EC Funded Network
Project on Rapid Prototyping in Medicine). What makes RP
technologies even more appealing is that they utilize
medical imaging data (obtained by techniques like com-
puted tomography - CT or magnetic resonance imaging -
MRI), almost directly, for the production of customized
patient specific parts. The reported medical applications of
RP technologies can be classified to the following
categories:
– Biomodelling, which involves the fabrication of phys-
ical models of parts of the human anatomy and
biological structures in general, for surgery planning
or testing.
– Design and fabrication of customized implants for
prosthetic operations, rehabilitation, and plastic surgery
– Fabrication of porous implants (scaffolds) and tissue
engineering
– Fabrication of specific surgical aids and tools
– Drug delivery and micron-scale medical devices
Despite their great flexibility and potential, RP technol-
ogies have not yet been widely adopted in the medical and
health-care sectors. This can be attributed to the high cost
and time required for the fabrication of corresponding
models which at present can only be justified in relatively
complex medical cases [4]. Besides time and cost, there is
the issue of accuracy of RP systems, which is not sufficient
for some applications, due mainly to poor or inaccurate
medical imaging data, as well as the issue of materials and
their properties, i.e., flexibility, strength and biocompatibil-
ity [5]. Nevertheless, RP technologies and AF in general
have great potential in the area of medical and health-care
applications due to their distinct features, and have been
therefore the subject of various studies worldwide. The
corresponding research covers various areas such as the
cost-efficient application of established technologies,
the development of new technologies, the virtual model-
ing/representation of medical data and the development of
biocompatible materials. The purpose of the present work is
to present and discuss in detail the most representative case
studies, covering the main research areas of AF applications
in medicine according to the classification given above.
2 Fabrication of RP models based on medical data
One of the major medical applications of RP is the
fabrication of models of parts of human anatomy of a
patient based on data obtained through the various well-
established techniques of CT or MRI [6]. The fabrication
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process of these physical models, which are nowadays
often called biomodels, involves three phases [7]:
– The first step is to obtain the data of the patient’s area
of interest with the use of the previously mentioned
techniques (CT, MRI, etc.), which provides an indirect
representation of the patient’s anatomy through a series
(stack) of 2D images.
– The images are next manipulated employing special
software, which facilitate the separation and highlight-
ing of the tissues (soft or hard) that represent the area of
the biomodel, and allow the conversion of the 2D
image information to a 3D representation. Usually, the
standard STL representation is utilized for the latter.
– Finally, the biomodel is fabricated via an RP system
followed by possible (if it is necessary) manual
finishing.
The accuracy of RP biomodels depends on various
factors associated with all phases of the process. Choi et al.
[8] analyzed the possible sources of error in SL biomodel-
ing and identified the main sources of error in the second
phase, namely, the translation of 2D data to a 3D virtual
model. This has led to the development of special software
tools like Mimics from Materialise Inc. (http://www.
materialise.com) and Biobuild (http://www.anatomics.com)
that have simplified and enhanced the accuracy of the 2D-
3D data transformation process. Regarding the manufactur-
ing accuracy of RP technologies, Santler et al. [9]
concluded that it is sufficient for clinical purposes.
3 RP biomodels for surgical planning
Among the first (and major) applications of AF/RP in
medicine and health care is the production of (physical)
biomodels that can be used as an aiding tool for surgical
planning and rehearsal [10]. Since every patient is unique,
the surgeon must fully understand the anatomy of the
patient before operation. Obtaining a full understanding of
the patient’s anatomy only by the study of a stack of CT/
MRI images in these cases requires great experience from
the surgeon, especially in complex surgical operations [11].
In such cases, RP biomodels greatly facilitate diagnosis and
treatment planning, and decrease the risk of misinterpreta-
tion of the medical problem. Having a physical biomodel in
hand also facilitates surgery planning and makes possible
the rehearsal and simulation of the operation through
marking, cutting and reassembling of the biomodel.
Furthermore, the pre-surgical study of a biomodel allows
not only the detailed evaluation of the operation, without
the time pressure present during actual operation, but also
possible problem prediction. This way, actual operation
time, and consequently operation cost and infection/
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anesthesia risk are decreased. Biomodels are also very
useful as a communication tool between medical personnel.
They are also very useful for the presentation of operation
details to people with no medical expertise (e.g., the patient
or its relatives), thus increasing consent and trust.
In most cases, RP is applied for the fabrication of models
of hard tissue parts of the human body, i.e., bones [12]. The
most widely reported application of RP biomodeling for
surgical planning is in the field of maxillo-craniofacial
surgery, which involves the surgical treatment of congenital
or acquired deformations (e.g., tumor resections or trauma
defections) both for functional and aesthetic purposes [13–
19]. The geometry of the skull is quite complex and cannot
be easily reproduced in a physical model using cutting
manufacturing methods like CNC milling. RP, therefore,
presents a reasonable alternative. Among RP technologies,
SL is the most commonly used in craniofacial biomodeling.
An example of an SL skull model, fabricated at the Center
of Product Development and Rapid Prototyping of the
University of Piraeus, is presented in Fig. 1. This SL model
is an accurate replicate of the damaged skull of a young girl
who was injured in a car accident and it has been used for
pre-operative planning of the surgery as well as an aid for
the design of the prosthetic implant that would restore the
anatomy of the damaged area.
Muller et al. [19] investigated the usefulness of RP
models of the skull in craniofacial and neurosurgical
practice. RP biomodels of 52 patients, whose treatment
required corrective/reconstructive cranioplasty or involved
complex surgical operations, were fabricated. They report
that SL models help in better understanding of the anatomy,
increase intra-operative accuracy, support accurate fabrica-
tion of implants, facilitate pre-surgical simulation and
improve education of trainees. Kermer et al. [17] propose
in their study an enhancement of the RP biomodeling
approach by investigating the possibility of selectively
colored RP biomodels. Their findings indicated that
Fig. 1 Skull biomodel of an injured girl for surgical planning
fabricated with SL
Int J Adv Manuf Technol (2009) 40:116–127
selectively colored models facilitate the management of
ablative surgery and reconstructive procedures as well. The
value of SL surgical biomodels has also been shown in the
case of reconstructing of complex orbital fractures in a
study by Fan et al. [20].
Biomodeling of soft-tissue parts of the human body using
RP, are rather rare in practice. This can be mainly attributed to
the difficulty of separating the area of interest from the
surrounding soft tissues, due to the relatively small differ-
ences of greyscale in medical scanned images. D’Urso et al.
[21] have studied the possibility of biomodeling of cerebral
aneurysms based on data obtained through CT angiography
(CTA) and MR angiography (MRA). Their results indicate
that the SL models are sufficiently accurate and can be quite
useful for surgical planning in complex cases or when the
standard imaging is felt to be equivocal. In a similar study
Wurm et al. [22] investigated the usefulness of cerebrovas-
cular biomodels for aneurysm surgery with similar results.
The feasibility of RP biomodeling for the replication of soft-
tissue parts is shown in the study of Binder et al. [23]. They
applied SL for the construction of replicates of the mitral
valve with good results.
Although the results of the previous mentioned studies
show the usefulness of biomodels for operation planning
and rehearsal, the high fabrication cost and time involved is
in most cases a major drawback. In particular, SL and SLS
models are very expensive and the associated cost can be
justified only in rather complex cases. In order to decrease
the fabrication cost and time, the utilization of 3D printing
is proposed, which is much less expensive and time-
consuming [24].
4 Tools for intra-operation guidance and testing
Of course, biomodels are not used in the pre-surgical phase
only. They are also used in actual surgery, during which,
biomodels or images obtained by biomodels, can be utilized
to guide the operation, assuring the accuracy and the quality
of results. D’Urso et al. [25, 26] investigated the possibility
of using accurate SL biomodels of the patient in planning
and rehearsing stereotactic surgery. The method of stereo-
taxy is a minimally invasive form of surgical intervention
which uses 3D coordinates in order to locate specific targets
and perform on them an operation like removal, implanta-
tion or injection. The location of the target is based on
MRI/CT data and is determined with respect to a reference
frame that is attached to the patient’s body. In order to
simplify the method and enhance its accuracy, D’Urso et al.
[25, 26] employed SL biomodels in a neurosurgical
operation. They report that biomodel-guided stereotaxy
offers significant advantages in terms of speed, simplicity,
accuracy, and versatility but with the extra cost and time
Int J Adv Manuf Technol (2009) 40:116–127
required for biomodel fabrication. Ngan et al. [27] also
proposed the use of RP models, fabricated with SL and
3DP, for preoperative and intraoperative planning of
pulmonary atresia surgical treatment. They report that the
surgeons found biomodels very useful in visualizing the
vascular anatomy, but construction of virtual models was
relatively labor intensive and required expert knowledge of
the pulmonary vasculature.
Another application of SL models is presented by Starly
et al. [28], in which the SL model is used as a medium for
the transfer of the anticipated skull geometry in a surgical
guidance system of over-laying images. In this approach,
the 3D virtual model of the patient’s skull is constructed
first through CT data interpolation. The virtual model is
then split in two symmetrical parts, the undamaged half and
the defective half that contains the trauma. Next, the
defective part is discarded and replaced by the mirror
image of the other half and a new virtual model of the skull
with the required symmetry is constructed and fabricated
with SL. The SL model is then scanned with CT and the
obtained stack of images is transferred to the surgery
guidance system, thus providing an image reference that
accurately guides the surgeon during operation.
SL has also been used for the fabrication of surgical
guides for the placement of dental implants, a restoration
process that requires detailed planning and high accuracy.
Sarment et al. [29] investigated the accuracy of dental
implant placement with the aid of SL surgical guides,
which according to their findings improved the implant
placement. In a similar study, Di Giacomo et al. [30] came
to the same conclusion, but denoted that the technique
requires improvement to provide better stability of the
guide during the surgery, in cases of unilateral bone-
supported and non-tooth-supported guides.
SLS and reverse engineering (RE) methods have been
employed for the construction of protective patient-specific
shielding masks that may be used as protective shields
during cancer treatment [31, 32]. The fabrication procedure
proposed by De Beer et al. [31] comprises of three phases:
first the face geometry for the mask is captured by 3D
photography, subsequently an SLS plastic mask is pro-
duced, based on the mask virtual model, and finally a radio
protective shell on the mask is applied through spraying of
a special metal alloy (see Fig. 2). The reported results show
that the proposed methodology leads to quicker and more
accurately manufactured masks compared to conventional
processes, at the expense of higher costs, the latter being
mainly associated with the SLS fabrication phase. Howev-
er, higher accuracy and better fit of masks are expected not
only to reduce the trauma experienced by the patient but
also to decrease production man-hours consumed, implic-
itly, therefore, increasing the cost-efficiency of the method.
The feasibility of the proposed procedure for the production
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Fig. 2 SLS lastic and metal sprayed shielding masks [31]
of customer-specific radiation shields is confirmed also in a
study by Zemnick et al. [32] who followed a similar
process that employs 3D laser scanning and SL.
Testing of new treating methods and technologies is
another field that RP has been applied successfully.
Johnson and Young [33] have investigated the feasibility
of using RP biomodels as expendable test parts, in an
experimental study of the response of the human head to
impact, during a car accident. In a similar manner, SL
models of cancellous bones, like those caused by osteopo-
rosis, were fabricated and mechanically tested, in order to
investigate the relationship between their geometry and
their mechanical strength, implicitly assessing fracture risk
[34]. Also, RP models of pelvic bones have been used to
prove experimentally the higher efficiency of computer-
assisted screw insertion procedures over conventional ones
in spinal surgery [35].
The study of exposure of the human respiratory system
to dangerous or pathogenic aerosols is another area where
RP models have been used successfully. Clinkbeard et al.
[36] applied SLS for the fabrication of human tracheobron-
chial airway models and carried out an experimental
investigation of the location and the amount of deposition
of dangerous aerosols under different conditions. They
propose the utilization of such models as the standard for
relevant studies.
5 Patient-specific implants
Another area in which the application of RP systems seems
to have great potential is the construction of customized
implants for reconstructive and plastic surgery. In this area,
the connection of medical imaging techniques and RP can
lead to significant time savings in operation time and much
higher accuracy and quality in surgical operation [37]. He
et al. [38] presented a design method for exact-fit
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customized implants that employs virtual and RP models of
injured or healthy bones in order to reduce the associated
time and cost. This methodology is employed in a case
study investigated by Truscott et al. [39] that focused on the
use of SLS models in the design process of customized
titanium elbow implants. According to their findings, the
complementary use of virtual and physical models greatly
improves the accuracy and reduces the cost of the implant
design process.
Winder et al. [40] present ten clinical cases in which the
required titanium implants for the reconstruction of skull
defects were created using RP models as masters for
casting. The geometry of the data was obtained by
comparing the defected side of the head to the contralateral,
so as to retain symmetry in the final result. Applying a
similar method, D’Urso et al. [41] used SL models of both
the actual defected side and the customized implant (the
latter to be used for casting acrylic implants) in cranioplasty
operations. They report reduced operating time and excel-
lent results at a ‘reasonable’ cost.
SL models have been used for the fabrication of
mandible titanium trays, which are implanted in the patient
as a replacement of the actual bone that was lost or
removed due to a tumor [42]. The implant SL model served
as the casting pattern for the construction of a silicon mould
and the subsequent casting of an identical wax model,
which was finally used as an expendable pattern for the
production of the titanium part by investment casting.
Singare et al. [42], who carried out this work, report that
using CT data and SL provides very accurate implants that
have significant functional and aesthetically pleasing
results. In a following study, Singare et al. [43] employed
Fig. 3 The SL pattern (a) for
the casting of the titanium joint
(b) and the negative pattern (c)
for the corresponding porous
bone (d) [44]
Int J Adv Manuf Technol (2009) 40:116–127
directly SL Quickcast models as expendable patterns for
investment casting of titanium implants. SL models have
also been used directly as expendable patterns for casting of
a titanium implant for the replacement of a damaged hemi-
knee joint [44]. In the same study, SL has also been
employed for the fabrication of an expendable mould for a
porous bone substitute (see Fig. 3). Both parts were
implanted on the patient with good results in terms of
functionality and fitting with the surrounding anatomy.
Dental applications generally seem rather suitable for RP
in view of the complex geometry involved, the low volume,
and the requirements for customization [45]. According to
Chang et al. [46], the integrated use of abrasive computer
tomography (ACT), RP, and CNC technologies can
significantly improve the speed and quality of the ortho-
dontic denture production process. Eggbeer et al. [47]
investigated the efficiency of using RP models as expend-
able casting models in the case of custom-made models of
removable partial denture (RPD) metal alloy frameworks.
These frameworks serve as a medium to retain artificial
replacement teeth in the oral cavity. According to their
method, RP models of the framework, which are fabricated
based on digitally scanned data of an impression of the
patient’s mouth, can be used as models for lost-wax casting
of the actual framework with great success. Fabrication of
titanium replicates of the actual teeth is also reported
possible using RP models and vacuum casting for the
production of teeth wax models for lost-wax casting [48].
Kruth et al. [49] provide an example of a direct application
of RP, particularly SLS, for the fabrication of metal-alloy
frameworks for dental prosthesis. Selective laser melting
(SLM) is another AF technology that according to Bibb et
Int J Adv Manuf Technol (2009) 40:116–127
al. [50] may be employed successfully for the direct
fabrication of chromium-cobalt customized RPD. The
feasibility of the SLM produced biocompatible implants
was also reported in [51]. Fabrication of titanium alloy
implants with direct laser forming, an AF technology that
constructs metal parts with bulk density, have also been
investigated also [52]. Direct fabrication of porcelain dental
restoration parts is investigated in [53]. The proposed
method involves the extrusion of dental powder pastes in
a layer-by-layer fashion and the solidification of the
extruded powder layer using a laser beam.
Using RP models as models for traditional casting
methods has been also investigated in cases concerning
soft tissue implants like ears [54, 55]. In these cases, the
geometry of the unaffected ear can be mirror-imaged using
reverse engineering (RE) methods, for example 3D laser
scanning, and reproduced with an RP method in order to
take an accurate symmetrical replicate of the lost ear (see
Fig. 4). Direct production of ‘soft’ biocompatible implants
employing available RP technologies requires the develop-
ment of new specialized materials. In order to address this
need, Bens et al. [56] developed a flexible (meth)acrylate-
based resin for SL that could be useful in various bio-
medical applications.
The versatility of RP methods may enable another route
for fabricating metal implants, which is the direct fabrica-
tion of a ceramic mould. Curodeau et al. [57] employ this
approach to fabricate ceramic shell with 3DP which are
used as expendable moulds for casting the desired implant.
The production of moulds for implants by RP was also
investigated by Hunt et al. [58], who employed SLS for the
fabrication of moulds for the production of wax investment
casting patterns. According to their findings, however, the
bone growth in implants fabricated this way is less than in
porous implants directly fabricated with SLS.
Fig. 4 Ear model manufactured with 3D printing to serve as vacuum
casting pattern for the fabrication of an ear substitute [54]
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6 Tissue and organism manufacturing engineering
Due to the additive nature of the processes incorporated in
RP technologies, they are also ideal for the fabrication of
implants with special geometrical characteristics, like
scaffolds for the restoration of tissues [59]. Scaffolds are
porous supporting structures that are used as a vessel for the
transplantation of tissue cells into the body of the patient
[60]. They serve as the platform for the rapid and guided
growth of new tissue in damaged or defective bones or even
organs of the human body. As in the cases of cranioplasty
and dental implants, RP technologies have been used either
as a direct method for manufacturing the scaffolds
themselves or (indirectly) as a ‘manufacturing tool’ of the
moulds required for the casting of scaffolds.
Chen et al. [61] present a case where an SL mould of the
intended scaffold geometry was used to cast an artificial
bone through injection of calcium phosphate cement (CPC),
which is a non-toxic soluble material and bone morpho-
genic protein. Tests performed on animals showed that the
artificial bone scaffold accelerated the growth of the actual
bone. The same approach has also been used in other
studies with similarly successful results in terms of cell
growth on the scaffold [62, 63]. Scaffold moulds for soft
tissue implants have also been fabricated by inkjet printing
technology with successful results [64, 65]. In this case, the
collagen scaffold was cast in the expendable RP mould,
which was subsequently removed by ethanol bathing. A
possible application of the method is presented by Taylor et
al. [66] that investigates aortic valves collagen scaffold
construction. Chen et al. [67] employed 3DP in a multi-
phase elaborate production process of nano-fibrous scaf-
folds with controlled architecture in macro-, micro- and
nano-scale. In the proposed process, 3DP is used for the
production of the moulds of PLLA scaffolds that could be
used in bone tissue engineering.
For direct fabrication of biocompatible scaffolds, several
RP methods as well as new AF methods have been
investigated. In most cases, the methods employed are
based on jet printing (3DP, MJM) or liquid deposition
techniques (FDM), that seem to be more appropriate for
direct scaffold fabrication, due to the ‘flexibility’ in the
selection of raw materials. Seitz et al. [68] presented a
method of direct 3DP of scaffolds from hydroxyapatite
(HA), a biocompatible implantable ceramic material. The
printed ceramic ‘green bodies’ are next cured in a high-
temperature furnace to allow sintering of the powder. In a
subsequent study Leukers et al. [69] performed a histolog-
ical evaluation of 3D-printed HA scaffolds which showed
that cells proliferated well into the scaffold, showing the
efficiency of this method for scaffold fabrication. HA
scaffolds have also been fabricated employing the FDM
[70] and robocasting methods [71]. Chim et al. [70]
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employed FDM for the construction of scaffolds with poly-
e-caprolactone (PCL) and HA-PCL scaffolds in order to
study different scaffold architectures and materials.
Dellinger et al. [71] used robocasting, an AF method that
consists of the robotic deposition of highly concentrated
colloidal suspensions in layers to form the scaffold
structure, which is subsequently sintered in high tempera-
ture. Miranda et al. [72] also investigated robocasting for
the construction of bioceramic scaffolds for bone tissue
engineering. The application of SLS technology for the
direct fabrication of biocompatible ceramic scaffolds has
also been extensively investigated. Williams et al. [73]
assessed the direct fabrication of PCL porous scaffolds.
According to their findings, the fabricated scaffolds had
sufficient mechanical strength and provided a sound
platform for the generation of the new bone. PCL-sintered
scaffolds SLS with a powder blend of polyetheretherketone
(PEEK) and hydroxyapatite (HA) has also been tried with
promising results [74]. The construction of liver tissues,
based on SLS-fabricated PCL scaffolds, has been investi-
gated by Huang et al. [75], who suggested that this
approach could, in the near future, lead to the development
of an implantable liver tissue equivalent for humans.
A problem apparent in most studies of RP-manufactured
scaffolds is the time required for the virtual design and
modeling of the scaffolds. 3D scaffold modeling is a trade-
off design process (porosity versus structural strength) that
requires considerable time and effort employing standard
mechanical design software. In order to circumvent this
problem, Chua et al. [76] suggested utilizing libraries of
application-specific polyhedral shapes that are used as
constructing elements of the scaffolds. A prototype system
that makes use of such primary scaffold elements (see
Fig. 5) was proposed by Naing et al. [77]. The system
utilizes special algorithms that construct the CAD scaffold
Fig. 5 3D models of possible
scaffold structures for CAD
scaffold modeling [77]
Int J Adv Manuf Technol (2009) 40:116–127
model according to user selected scaffold elements and
porosity, and based on a surface model that provides the
outer geometry of the scaffold. A micro-SL system that
could be used for scaffold architecture studies is presented
in [78]. According to Lee et al. [78], the redesigned system
is capable of fabricating highly accurate 3D polymer
structures that could aid the scaffold design process.
Due to the material physical and chemical properties of
the models, RP-assisted scaffold fabrication has been
mainly focused on bone (hard) tissue engineering. For the
fabrication of soft tissue scaffolds, new techniques like 3D-
bioplotting are under investigation and development [79].
3D-bioplotting is a technique that resembles continuous
deposition RP technologies like FDM and allows 3D
dispensing of liquids and pastes in liquid media through a
pressure-controlled dispenser. Moroni et al. [80] employed
3D-bioplotting in the fabrication process of 3D hollow
fiber scaffolds from biocompatible polymeric blends. Fiber
hollowing is achieved by selective dissolution of the fiber
inner core polymer by extensive immersion of the initial
scaffold in solvent. Viscoelastic properties of the obtained
scaffolds can be modulated to accomplish mechanical
requirements for tailored tissue engineering applications
[81]. 3D fiber deposition of metallic scaffolds for orthope-
dic applications has also been reported [82].
An emerging concept based on the primary successful
research results of AF applications in tissue engineering is
the concept of organism manufacturing engineering (OME).
OME is defined as the science and technology that utilizes
the principles and methods of modern manufacturing
science and life science through controlled direct or indirect
3D assembly of cells in order to manufacture live
organisms to substitute or to repair human tissues and
organs [83]. According to Xiong et al. [83], the main
principles of AF could serve as the basis of new OME
Int J Adv Manuf Technol (2009) 40:116–127
technologies for direct or indirect controlled cell assembly,
and thereby provide a solution to the ever-increasing
demand for donor organs. Yan et al. [84] proposed a new
process for the production of scaffolds for bone tissue
engineering. Their method (low-temperature deposition
manufacturing – LDM) employs the layer manufacturing
principle and an extrusion-type system for the construction
of PLLA/TCP composite scaffolds. Compared to estab-
lished methods like FDM, the LDM process is reported to
preserve bio-activities of scaffold materials because of its
non-heating liquefying processing of materials. In a
following study [85], LDM was investigated as a produc-
tion method for implantable bioactive liver substitute with
promising results.
A similar extrusion-type method is proposed by Vozzi et
al. [86] for the fabrication of PLGA (polylactic-co-glycolic
acid) scaffolds with microporosity. In the described method,
material is deposited utilizing a pressure micro-syringe and
a three-axis system with micro-scale positioning accuracy.
In [87], a comparison of four types of nozzle systems, i.e.,
pneumatic microvalve, solenoid microvalve, piezoelectric
and precise extrusion deposition (PED) nozzles that deposit
sodium alginate and PCL solutions was carried out. The
proposed multi-nozzle manufacturing system can be
employed used for the fabrication of bioactive tissue
scaffolds, automatic cell loading, and heterogeneous tissue
constructs for emerging regenerative medicine. Direct
fabrication of 3D neural constructs by jet printing AF has
also beeninvestigated [88]. The method proposed by Xu et
al. [88] employs conventional inkjet printing technology
modified for alternating deposition of neural cell layers and
biodegradable fibrin gel layers that form a cohesive 3D
neural sheet. Examination of the sheets showed that
deposited neurons maintained their basic electrophysiolog-
ical functions.
7 Drug delivery and microscale devices
Another field in which RP technologies are expected to
prove very useful is the fabrication of customized micro-
systems and therapeutic devices for controlled highly
specific and precise drug delivery. Such devices involve
complex micron-scale networks of fluidic and electronic
components capable of operating in an integrated manner
[89]. In their study, Razzacki et al. [89] categorized these
devices into three major groups:
– Biocapsules and microparticles for controlled and/or
site-specific drug release,
– Microneedles for transdermal and intravenous delivery
and
– Implantable microsystems.
123
An example of a biomedical device that may be used in the
area of drug testing and DNA research is reported in [90]. The
device presented is a biochemical laboratory in micron-scale
that may be used for cell-free protein synthesis. This micro-
scale laboratory is assembled by biochemical chips fabricat-
ed with the method of hybrid micro-SL, in which the chip
functional parts such as one-way valve, ultrafiltration
membrane and photo sensor are inserted during the layer
construction-solidification process, thus eliminating the
subsequent chip-assembly phase. A novel layer manufactur-
ing method that could possibly be applied in biosensor
development, tissue engineering, drug delivery, and bioma-
terials, is described by Kýzýlel et al. [91]. The proposed
method permits the construction of the PEG-based hydrogel
multilayer structures. Reported advantages are the biocom-
patibility of materials and the fact that layer formation is
achieved in mild photopolymerization conditions using
visible instead of ultraviolet light.
The fabrication of medical microdevices or microcon-
structions that are biodegradable (and therefore require no
special removal operation from the patient’s body) is
another possibility investigated in conjunction with AF.
Methods employed traditionally for micro-scale manufac-
turing like thin-film deposition, photolithography, etching,
or methods borrowed from the computer industry, are not
suitable for biodegradable polymers [92]. In such applica-
tions, non-invasive additive fabrication technologies, like
micro-SL, may have great potential in both a laboratory and
industry scale [92]. Matsuda and Mizutani [93] reported the
development of two such photocurable biodegradable
liquid copolymers, one hydrophilic and another hydropho-
bic. Reported results show that the developed copolymers
can be easily photocured by UV radiation and are therefore
suitable for use in micro-SL (see Fig. 6). Itoga et al. [94]
presented a novel photolithography device that could be
Fig. 6 Microneedle array fabricated with micro-stereolithography [93]
124
employed in the preparation of micro-patterned surfaces for
biomedical applications as well as other microfluidic
surfaces in a rapid prototyping manner. The device is based
on a modified LCD projector and has been tested in the
construction of polyacrylamide (PAAm) micro-patterned
surfaces. Shape deposition manufacturing (SDM) is another
RP method that could be potentially employed for micro-
scale manufacturing. Cheng and Lin [95] presented such an
application of SDM in the fabrication of valve-less micro-
pumps with micro channels.
AF may provide alternative ways for the fabrication of
drug-delivery devices like oral tablets. Rowe et al. [96]
presented an application of 3DP technology for the fabrica-
tion of oral devices where two different release mechanisms,
erosion and diffusion, are mixed in a single device. Other
possible applications are tablets with a quick dissolve region
that break into controlled subunits and pulsatory devices. The
SLS process has been also used for the fabrication of porous
cylindrical disc matrices that may be used as drug delivery
devices by Low et al. [97]. They reported that it is possible to
use SLS for producing drug-delivery devices that have
variable porosity and micro-features. Leong et al. [98]
investigated the possibility of building biodegradeable
controlled drug-delivery devices with SLS. Their experi-
ments with PCL and PLLA as test materials showed that
varying porosity discs can be produced by controlled
variance of SLS fabrication parameters.
8 Discussion and concluding remarks
In this paper, applications of AF/RP technologies in
medicine and current research issues in the field of rapid
medical prototyping are presented. The review of the
international specialized literature showed that custom
biomodels fabricated with RP technologies are quite useful
for planning and the rehearsal of complex surgical
operations. According to the results of most studies, RP
biomodels aid the surgeons in diagnosis, planning, problem
prediction and communication, thus reducing operation
time infection risk and improving the results of the
operation.
Among the RP technologies applied to medicine, SL
seems to have attracted the attention of most researchers.
SL is not only relatively more accurate but also the number
of installed SL systems worldwide is very big. Also, SL
resins provide the advantage of biomodel clarity and
transparency that can be quite useful in surgery rehearsal.
However, they are not biocompatible and require special
handling; a fact that makes adoption of SL systems in the
hospital environment difficult. Both the accuracy and the
low surface roughness of SL biomodels makes them ideal
as casting patterns for the fabrication of customized
Int J Adv Manuf Technol (2009) 40:116–127
metallic or acrylic implants through lost-wax or vacuum
casting methods.
For the fabrication of biomodels for surgery planning and
evaluation purposes, less ‘expensive’ or time-consuming RP
technologies, like multicolor 3DP and FDM seem to be the
most suitable choice. Another advantage of these two
technologies is that they are office-friendly and can process
biocompatible materials with some minor modifications.
Further reduction in the fabrication time involved can be
achieved through higher automation of the medical imaging
data manipulation process that is required for the construction
of the virtual model. The virtual model construction phase is
reported as the main source of observed inaccuracies, mainly
due to the low level of detail and information that can be
obtained through conventional medical imaging (diagnostic)
systems.
SLS technology has the greatest potential among
commercial RP technologies or direct fabrication of
implants. This is mainly due to the fact that SLS can
fabricate implants from a variety of materials including
metals, ceramics and thermoplastics with sufficient accura-
cy. In this context, the main research issue is to develop and
test materials that are biocompatible so that can be used
safely for direct fabrication of implants.
Fabrication of custom-made scaffolds is another appli-
cation in which RP can be quite useful. Two approaches
have been identified:
– Direct Methods – they employ a commercial RP system
or a new AF method for the fabrication of the actual
scaffold itself (e.g. SLS of biocompatible ceramics) and
– Indirect Methods – they employ RP for the fabrication
of the tool (pattern or mould) that will be used for the
production of the actual scaffold.
Due to adverse materials properties direct additive
scaffold fabrication is mostly directed to hard-tissue
scaffolds (bone tissue engineering). As far as the fabrication
of soft-tissue scaffolds new manufacturing methods that
apply the principles of AF are currently under development.
These new methods employ mostly the jet-printing or
deposition operational principles for the construction of
layers from biocompatible or biodegradable materials. An
aspect that should be considered in scaffold fabrication with
powder based RP technologies is the removal of trapped
material within the scaffold (trapped volume problem).
Also, the minimum grain size sets a limit in the porosity
obtainable with these methods. However, the development
of finer grain powder materials could greatly alleviate these
drawbacks. Obviously, full exploitation of the advantages
of AF technologies is directly related to the availability of
special design software systems (Bio-CAD) that enable
design and manipulation of the relatively complex geom-
etries of scaffolds. Scaffolds also present a challenge in
Int J Adv Manuf Technol (2009) 40:116–127
terms of virtual representation that cannot be easily
manipulated by currently available industrial CAD systems.
Micro- and nano-fabrication variants of AF technologies
are expected to make possible the fabrication of controllable
drug-delivery units or implants in the micron or the submicron
level. For custom implants of such fine scale require further
improvement of associated technologies such as micro-CT.
Fabrication of artificial organ substitutes is a very interesting
area of research, where initial results show that extrude-type
AF may be employed successfully. Relevant technologies
under development mostly focus on deposition techniques
that enable controlled ‘assembly’ of living cells and support-
ing material in order to construct the organ substitute.
In conclusion, the literature review carried out in this work
showed that although RP technologies exhibit a great potential
in the field of medical applications, they have not been widely
adopted yet in standard medical practice because of the high
cost and fabrication time involved. Although RP is faster and
more flexible than other manufacturing methods (e.g., CNC
machining) it is neither fast enough nor cost-effective to cater
for emergency cases. Depending on the size and complexity of
the biomodel, RP fabrication times vary between a few hours
up to 2 days, which may be unacceptably long for emergency
cases (depending, of course, on the particular case). Time and
cost requirements, therefore, restrict the utilization of RP to
rather complex cases where considerable cost savings and
quality benefits are expected. Indeed, this is the case with
surgical planning biomodels. Also, RP cost and time
‘expenses’ seem to be justifiable for custom implant fabrica-
tion applications, e.g., for orthopedic surgery, simply because
in such cases the utilization of conventional manufacturing
methods, implies significantly higher fabrication time and
cost. Furthermore, the customization of the implant assures
accurate fitting, reduces operating time and enhances quality.
Ill-fitted implants cause discomfort and should be replaced
quite frequently, which means that the cost of rectifying or
compensating the effects of an ineffective surgery can be far
higher than the cost of the actual surgical operation itself [24].
Considering, therefore, these compensating costs, the initial
investment cost in RP may be well justified. Regarding
tissue engineering, artificial organ manufacturing and drug-
delivery device fields, initial experimental results show that
there is a great potential. However, a lot of research effort is
still required for the development of reliable manufacturing
systems and materials, which could be employed for the
mass production of scaffolds or even organ substitutes.
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