Biomaterials 83 (2016) 127e141

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Biomaterials
journal homepage: www.elsevier.com/locate/biomaterials

Review

Topological design and additive manufacturing of porous metals for

bone scaffolds and orthopaedic implants: A review
Xiaojian Wang a, 1, Shanqing Xu a, 1, Shiwei Zhou a, Wei Xu b, Martin Leary b,
Peter Choong c, M. Qian b, Milan Brandt b, Yi Min Xie a, b, *
a
Centre for Innovative Structures and Materials, School of Engineering, RMIT University, GPO Box 2476, Melbourne 3001, Victoria, Australia
b
Centre for Additive Manufacturing, School of Engineering, RMIT University, GPO Box 2476, Melbourne 3001, Victoria, Australia
c
Department of Surgery, University of Melbourne, St. Vincent's Hospital, Melbourne 3001, Victoria, Australia

a r t i c l e i n f o a b s t r a c t

Article history: One of the critical issues in orthopaedic regenerative medicine is the design of bone scaffolds and im-
Received 23 July 2015 plants that replicate the biomechanical properties of the host bones. Porous metals have found them-
Received in revised form selves to be suitable candidates for repairing or replacing the damaged bones since their stiffness and
31 December 2015
porosity can be adjusted on demands. Another advantage of porous metals lies in their open space for the
Accepted 1 January 2016
Available online 6 January 2016
in-growth of bone tissue, hence accelerating the osseointegration process. The fabrication of porous
metals has been extensively explored over decades, however only limited controls over the internal
architecture can be achieved by the conventional processes. Recent advances in additive manufacturing
Keywords:
Additive manufacturing
have provided unprecedented opportunities for producing complex structures to meet the increasing
Topology optimization demands for implants with customized mechanical performance. At the same time, topology optimi-
Bone scaffold zation techniques have been developed to enable the internal architecture of porous metals to be
Porous metals designed to achieve specified mechanical properties at will. Thus implants designed via the topology
Orthopaedic implants optimization approach and produced by additive manufacturing are of great interest. This paper reviews
Biomaterials the state-of-the-art of topological design and manufacturing processes of various types of porous metals,
in particular for titanium alloys, biodegradable metals and shape memory alloys. This review also
identifies the limitations of current techniques and addresses the directions for future investigations.
© 2016 Elsevier Ltd. All rights reserved.

1. Introduction
Bone is a complex tissue that continually undergoes dynamic
biological remodelling, i.e., the coupled process whereby osteo-
clasts resorb mature bone tissue followed by osteoblasts that
generate new bone to maintain healthy homeostasis of bone [1].
This unique feature of bone underpins its ability to remodel itself to
repair damage. However, when a bone defect exceeds a critical non-
healable size, external intervention is required to supplement self-
healing if the defect is to be bridged [2]. Despite recent advances in
biomaterials and tissue engineering, repair of such a critical-sized
bone defect still remains a challenge. The optimal choice is to use
autograft (patients' own tissue) [3]. However, harvesting autograft
* Corresponding author. Centre for Innovative Structures and Materials, School of
Engineering, RMIT University, GPO Box 2476, Melbourne 3001, Victoria, Australia.
E-mail address: mike.xie@rmit.edu.au (Y.M. Xie).
1
Equal contribution.
tissue creates the morbidity associated with a second surgical site.
An alternative choice is allograft tissue (taken from another per-
son), which carries the risk of transmissible disease and depends on
logistic circumstances (limited availability). The insufficiencies of
application of autograft and allograft tissue have led to greater
research efforts to identify biomimetic materials and structures
that are suitable for skeletal repair without the inherent problems.
Metals and alloys have a long history of application as bone
implants [4e7]. Among them, the use of stainless steels, cobalt (Co)
based alloys (CoCrMo), and titanium (Ti) and its alloys are well
established due to their good biocompatibility, satisfactory me-
chanical strength and superior corrosion resistance [5]. However,
implants made of these materials are usually much stiffer than
natural bones, leading to stress shielding - a major source for bone
resorption and eventual failure of such implants [5]. Cortical bone
(compact bone) has elastic moduli ranging from 3 to 30 GPa, while
trabecular or cancellous bone has significantly lower elastic moduli
of 0.02e2 GPa. Most current implant materials have much higher

http://dx.doi.org/10.1016/j.biomaterials.2016.01.012
0142-9612/© 2016 Elsevier Ltd. All rights reserved.
128 X. Wang et al. / Biomaterials 83 (2016) 127e141

moduli than those of bones, e.g., Ti6Al4V has a modulus of around producing porous metallic structures for bone tissue repair, with a
110 GPa and CoCrMo alloys have a modulus of around 210 GPa particular emphasis on topological design of internal architecture
[5,6,8]. Therefore, to avoid stress shielding at the bone-implant of porous metals for bone implants.
interface, the equivalent Young's modulus and yield stress have to
be adjusted when using these bulk materials. An effective method
2. Structure and properties of bone
is to introduce adjustable porosity or relative density as proposed
by Gibson and Ashby [9] for isotropic materials.
2.1. Structure of bone
Traditional methods for fabricating open-cell porous metals
include liquid state processing (direct foaming, spray foaming, etc.),
Bone is a natural composite containing both organic compo-
solid state processing (powder metallurgy, sintering of powders
nents (mainly type-I collagen, but also type-III, type-IV collagen
and fibres, etc.), electro-deposition and vapour deposition [10,11].
and fibrillin) and inorganic crystalline mineral (e.g., hydroxyap-
Although the shape and size of the pores can be adjusted by
atite, HA) [1,22,33,34], as illustrated in Fig. 2. The structure of
changing the parameters of these manufacturing processes, only a
bone is similar to reinforced concrete that is used in the building
randomly organized porous structure can be achievable. However,
industry. The function of HA crystals and collagen molecules are
additive manufacturing (AM) technologies can fabricate porous
like the steel rod and cement to concrete: one part provides
metals with predefined external shape and internal architecture
flexibility and the other provides strength and toughness. Type-I
[2,12e14]. Metal-based additive manufacturing (MAM) techniques,
collagen is a triple helix of ~1.5 nm in diameter and ~300 nm in
such as selective laser melting (SLM) and electron beam melting
length. It is the primary organic components of bone. Other non-
(EBM), are computer controlled fabrication process based on layer-
collagenous proteins include glycoproteins and bone specific
wise manufacturing principles. SLM [15e17] and EBM [18,19] are
proteoglycans [1]. Hydroxyapatite is the inorganic component of
increasingly used for the fabrication of porous metals with complex
bone and is plate-shaped of 50
25 nm in size and 1.5e4 nm
architecture. Instead of using electron beam as the energy source in
thick [35]. The HA crystals are oriented in a periodic array in the
EBM, the SLM technology uses laser beam with adjustable wave-
fibrils, preferentially with their c axis parallel to the collagen fi-
length. Therefore, EBM can only process conductive metals
brils [35]. These two phases account for about 95 wt. % of the dry
whereas SLM can process polymer or ceramics as well as metal.
bone.
Furthermore, due to more diffuse energy (larger heat-affected
Bone has a hierarchical structure. Each level performs diverse
zone), EBM process has larger minimum feature size, median
mechanical, biological and chemical functions. The hierarchical
powder particle size, layer thickness, resolution and surface finish
levels of bone include macroscale, microscale, sub-microscale,
[20]. The robust application of MAM technologies requires exten-
nanoscale, and sub-nanoscale (Fig. 2). The macroscale level rep-
sive material, process and design knowledge, specific to each MAM
resents the overall shape of the bone. Bone can be classified as
technology [21]. MAM system behaviour is subject to significant
compact bone (cortical bone), and trabecular bone (cancellous
stochastic error and experimental uncertainties, requiring that
bone). Compact bone is almost solid, with only ~3e5% spaces for
“assumptions are necessary to simplify the problem” [22]. Sources
osteocytes, canaliculi, blood vessels, and erosion cavities etc.
of error include: complex and transient heat transfer phenomena
There are large spaces in trabecular bone. The pores in trabecular
[23], geometric effects [24] with poorly defined powder thermal
bone are filled with bone marrow, and the porosity varies be-
properties [25]. MAM prediction error can lead to excess melt pool
tween 50 and 90% [1,36e38]. The building block of compact bone
temperature [26], resulting in undesirable microstructure, residual
is the osteons, which are of the size ranging from 10 to 500 mm,
stress, local porosity, and surface roughness. Understanding the
whereas the trabecular bone is made of a porous network of
effects of design decisions on temperature related process defects is
trabeculae. At the micron- and nano-scales, aggregated type-I
critically important to the process control. Comprehensive reviews
collagen and HA form the collagen fibril. The reinforced
of AM technologies can be found elsewhere [27,28].
collagen fibre is a universal building element for both compact
Recent successes in orthopaedic regenerative medicine have
and trabecular bones.
promised an exciting future of AM technology. The world's first
additively manufactured mandible was implanted in a patient by
Dr. Jules Poukens and his team in 2012 in Belgium [29]. A full lower 2.2. Mechanical properties of bone
jaw implant (mandible in Fig. 1) was coated with hydroxyapatite
and implanted in an 83 year old lady. The porous implant was Mechanical properties of bone vary significantly with age,
slightly heavier than a natural jaw, and provided robust attachment anatomical site and bone quality. It continues to be a major scien-
of muscles and sufficient space for nerves [29]. Skull re- tific challenge to fully understand the mechanics of living bones
constructions with AM parts have been performed successfully by [36e38]. Among the various biomechanical properties of bone
using digital design and AM. Mertens et al. [30] successfully (stiffness, strength, creep and fatigue), elastic modulus has attrac-
reconstructed a class III defect using AM manufactured titanium ted the most research interest because of its critical importance for
implants, which provided both midfacial support and a graft fixture characterizing various bone pathologies and guiding artificial
(midface defect in Fig. 1). Jardini et al. [31] in Brazil designed and implant design. The elastic modulus and strength of bone are
AM fabricated a customized implant for the surgical reconstruction anisotropic. Compact bone is both stronger and stiffer when loaded
of a large cranial defect. In 2014, Prof. Peter Choong, an Australian longitudinally along the diaphyseal axis than the radial transverse
surgeon from St Vincent's Hospital, together with scientists from directions (Table 1). It is also stronger in compression than in
the Commonwealth Scientific and Industrial Research Organization tension. Trabecular bone is an anisotropic and porous composite.
(CSIRO) and Anatomics, successfully implanted the world's first 3D- Like many biological materials, trabecular bone displays time-
printed titanium heel bone into a patient [32]. dependent behaviour as well as damage susceptibility during cy-
Typical design and application approaches of porous metallic clic loading [41]. The mechanical properties of trabecular bone
implants normally include the design of scaffold, AM and post- depend on not only the porosity, but also the architectural
processing (heat-treatment and surface modification) as illus- arrangement of the individual trabeculae. The physical and me-
trated in Fig. 1. This review aims to identify the current status and chanical properties of human bone are summarized in Table 1
the future directions of design-oriented AM technology in (values are averaged from reported data) [1,26,34,36e38,42,43].
 X. Wang et al. / Biomaterials 83 (2016) 127e141 129

Fig. 1. Schematic diagram for the design, additive manufacturing, heat-treatment, surface modification of porous metallic structures and the latest orthopaedic regenerative
medicine examples. Images adapted from Refs. [29e31].

Fig. 2. Hierarchical structural organization of bone. Image adapted from Refs. [35,39,40].

2.3. Requirements for the design of orthopaedic implants
A successful porous metallic implant would restore the function
of bone and promote regeneration of bone tissue at the damaged
site. An ideal bone scaffold should possess the following
characteristics: (1) biocompatibility; (2) suitable surface for cell
attachment, proliferation and differentiation; (3) highly porous
with an interconnected pore network for cell ingrowth and trans-
port of nutrients and metabolic waste; (4) mechanical properties to
match the requirements of the surrounding tissues to reduce or
130 X. Wang et al. / Biomaterials 83 (2016) 127e141
Table 1
Mechanical properties of human bones, average values from literature [1,26,34,36e38,42,43].
Porosity Modulus (GPa)
Compact Bone 3e5% Longitudinal
Transverse
Shear
Trabecular Bone Up to 90% Vertebra
Tibia
Femur
eliminate stress shielding, and to meet anatomic loading re-
quirements to avoid mechanical failure [44e48]. Porous metals are
implanted to repair bone defects of critical size and, in most cases,
serve as load-bearing devices. Bone is usually anisotropic with
different stiffness and strength in different directions, but normally
there are no extremely weak directions [49]. Therefore, suitable
porous metals will approximate the stiffness of surrounding bones,
making them effective for load transfer and alleviating the stress
shielding effect.
The key characteristics to design porous metallic implants
include the careful selection of porosity, pore size, and pore inter-
connectivity, aiming to achieve satisfactory clinical outcomes.
These structural features have a profound effect on mechanical
properties and biological performance of the metallic implants.
Bone regeneration in porous implants in vivo involves recruitment
and penetration of cells from the surrounding bone tissue and
vascularization [50]. Higher porosity may facilitate these processes
and benefit the bone ingrowth. For instance, more bone ingrowth
was found in porous titanium coatings of higher porosity after the
implants were placed into a canine model for 8 weeks [51]. Simi-
larly, bone ingrowth was shown to be deeper and greater in porous
polymer scaffolds of higher porosity [52].
The influence of pore size on the bone ingrowth is still contro-
versial in literature [53e57]. The optimal pore size for mineralized
bone ingrowth is claimed to be 100e400 mm in the research by Itala
et al. [53]. They implanted triangle-shaped titanium implants of
different plate thickness with pore size ranging from 50 to 125 mm
into rabbit femur and found that there was no clear lower limit of
pore size for consistent bone ingrowth [53]. Recently Braem et al.
[55] assessed the feasibility of early bone ingrowth into a pre-
dominantly microporous Ti coating in the compact bone of rabbit
tibiae and found that new bone formed in micropores of less than
10 mm. Large pores are believed to favour vascularization. Bai et al.
[56] suggested an upper limit of pore size for vascularization, 400
mm, beyond which no significant difference was observed with
increasing pore size. Kuboki et al. [54] found that, when the pore
size ranged from 300 to 400 mm, the implantation of porous hy-
droxyapatite scaffolds into rats showed higher alkaline phosphates
activity, osteocalcin content and bone ingrowth. However, Naoya et
al. [57] implanted 300 mm, 600 mm and 900 mm AM manufactured
porous Ti scaffolds into rabbit tibia and they found 600 mm and 900
mm scaffolds demonstrated significantly higher bone ingrowth than
300 mm scaffolds. In addition to vascularization, specific surface
area of scaffolds is another essential factor with respect to fixation
ability. Scaffolds with smaller pores are considered to have larger
surface area and therefore more space for bone tissue ingrowth.
Another important feature of bone implants is the permeability
of the porous metal since the transportation of cells, nutrients and
growth factors require the flow of blood through the porous scaf-
folds. In simple terms, permeability is characterised by using
gradient pressure to push liquid through porous material. Zhang
et al. [58,59] stated that permeability may influence vascular
Strength (MPa) Poisson's ration
17.9 ± 3.9 Tension 135 ± 15.6 0.4 ± 0.16
Compression 205 ± 17.3
10.1 ± 2.4 Tension 53 ± 10.7 0.62 ± 0.26
Compression 131 ± 20.7
3.3 ± 0.4 Shear 65 ± 4.0
0.067 ± 0.045 2.4 ± 1.6
0.445 ± 0.257 5.3 ± 2.9
0.441 ± 0.271 6.8 ± 4.8
invasion and the supply of nutrients required to sustain cell growth
and may also provide an outlet for the removal of cell debris,
thereby increasing its osteoconductive potential. High permeability
of titanium implants enhances the osseointegration process
[58,59]. Further research on the effect of permeability of porous
metallic implants is in demand.
In summary, porosity, pore size and pore interconnectivity are
key factors that will significantly influence the mechanical prop-
erties and biological performance of scaffolds such as bone
ingrowth and transportation of cells and nutrients. However, the
effects of these factors on scaffold performance are complicated,
even conflicting to each other in certain circumstances. For
example, increasing the porosity may enhance the biological pro-
cesses, but it can decrease the stiffness and strength drastically [9].
Therefore, finding the optimal topologies for scaffolds is of critical
importance. However, conventional CAD-based design techniques
are inefficient and usually fail to obtain the optimal scaffold design
because a prohibitively large number of trials would be required in
order to achieve a balanced performance, e.g., desirable stiffness
and good permeability. On the contrary, topology optimization
techniques are capable of quickly finding the optimal topologies
which satisfy multiple objectives and constraints simultaneously to
provide site-specific biological performance.
3. Topological design of porous metallic structures for
orthopaedic implants
3.1. Porous metallic implants and topology optimization techniques
As mentioned previously, bone is a 3D inhomogeneous structure
with elaborate features from macro-to nano-scales. While it is
impossible, and perhaps unnecessary, to recreate all details of
natural bone in the porous metallic implant, ideally the implant
should have similar hierarchical configurations on multiple scales.
It is essential that the implant should possess properties similar to
the host bone and the ambient tissue [60]. This calls for a well-
established design methodology integrating structural stiffness
with fluid permeability to allow the implant to have both adequate
rigidity to resist the physical loading and sufficient permeability to
transfer cells, nutrients, etc. Fully solid metals, e.g. titanium, are
unsuitable because they are inherently impermeable, preventing
cells from invading inside to proliferate and form extra cellular
matrix. Moreover, the Young's modulus of human bones (Table 1) is
much lower than that of solid metals. Such a stiffness mismatch is
regarded as one of the most significant problems in implant design
as the resulting stress shielding would often lead to implantation
failures.
Recently, porous metals were used in orthopaedic surgeries to
replace damaged bones. Porous scaffolds are geometrically similar
to natural hard tissues which are composed of constituting ma-
terials penetrated by interconnected pores [61]. Porous metals can
be designed to duplicate the properties of bones if their structures
 X. Wang et al. / Biomaterials 83 (2016) 127e141 131

Fig. 3. Approaches for scaffold design: representative unit cells and blocks. Images adapted from Refs. [14,62e64,71,72,74,80,106e108].

could be designed digitally and fabricated using advanced consist of a vast number of randomly shaped pores in different
manufacturing technology. Conventional porous scaffolds typically sizes and therefore it is almost impossible to quantitatively analyse
132 X. Wang et al. / Biomaterials 83 (2016) 127e141
their properties. To obtain a simplified model, researchers usually
assume that scaffolds are constructed of periodically-repeating
unit cells along all directions and the architecture of the micro
unit cells can distinctly define the macro properties of the scaf-
folds. Typical traditional design strategies of periodic bone scaf-
folds include Computer Aided Design (CAD), image-based design
and implicit surfaces [62], as illustrated in Fig. 3. CAD-based design
are obtained by using various CAD tools. The widely used library of
constructing units always involves Platonic and Archimedean
polyhedral solids, which can also be used to construct functional
graded scaffolds [63e66]. Computer-aided system for tissue scaf-
folds (CASTS) is a further development based on these scaffold li-
braries, aiming to efficiently automate the entire design process for
desired topologies [67e69]. Bio-inspired design is an alternative to
improve the mechanical performance of bone scaffolds and enrich
the scaffold library [70e72]. Other CAD-based approaches may
also be used in designing scaffolds [14]. Image-based design, as
proposed by Hollister et al. [73], is based on Computed Tomogra-
phy (CT) or Magnetic Resonance Image (MRI) data for recon-
struction of a defect. It uses Boolean combination of defect image
and architecture image (could be from empirical or bio-inspired
shapes) to create 3D scaffold image [12,73e75]. Implicit surface
modelling uses single mathematical equations to freely introduce
pore shapes such as triply periodic minimal surfaces (TPMS),
which is highly flexible in designing scaffolds [62,76e80]. CAD-
based randomization approach starts from cell elements to fill a
specific volume in computer software, where standard cell ele-
ments are usually packaged while new cell elements can also be
created [81,82]. This method can effectively imitate real bones by
the randomization process, thus promoting the bone attachment
and bone cell in-growth, as well as increasing the damage
tolerance.
While the aforementioned methods enable scaffolds to obtain
desirable stiffness and permeability, these approaches demand a
vast number of attempts to achieve anticipated properties. Often
the resulting design is far from the optimum. One of the main
challenges in the application of porous scaffolds to orthopaedic
implants is the adaptation of their mechanical and biomedical
properties to those of natural bones. The implanted scaffolds are
placed in a complex environment and their performance is affected
by many factors. Some of them such as high permeability and good
stiffness are competing with each other since a larger pore size is
obtained usually at the cost of a lower mechanical strength [83].
Hence, to increase the mass transfer, while retaining a strong
supporting framework, there is a need to maintain a delicate trade-
off between the porosity of the fabricated scaffold and its strength
[10].
Topology optimization e a mathematical method capable of
rearranging the materials to attain desired properties while
satisfying prescribed constraints e can complement the trial-and-
error approach and provide a powerful tool to design complex
scaffolds with features on multiple scales. It is a branch of
computational mechanics and was originally developed in struc-
tural engineering [84]. It has been widely used for designing
structures and materials for desirable mechanical performance
and physical properties. Through two decades of development, this
method has gone far beyond the traditional structural engineering
context [85].
Typically, there are two ways to define a structure in topology
optimization. The first is a point-by-point description in which a
void (r ¼ 0) or a solid (r ¼ 1) phase in a local element is represented
by an elemental density r [86]. The Evolutionary Structural Opti-
mization (ESO) [87,88] and the Solid Isotropic Material with
Penalization (SIMP) methods [86,89] use this type of description
and have gained considerable success in solving a wide range of
engineering optimization problems. In the field of computational
material design, the topology optimization approach is termed as
an “inverse homogenization” method because the homogenization
method [90,91] is used to calculate the effective properties of a unit
cell and the material distribution is rearranged through topology
optimization to enable the material to attain target properties. The
seminal work of inverse homogenization was conducted by Sig-
mund in the 1990s for the design of materials with prescribed
elastic properties [92,93]. Thereafter, great achievements were
obtained in the design of exceptional material properties including
negative thermal expansion coefficient [94] and negative refraction
index [95]. Later, this method was extended to the design of scaf-
fold materials with their stiffness matrices matching those of
anisotropic native bones [75,96,97]. By using the SIMP based
structural optimization, Guest and Prevost [98] developed a to-
pology optimization technique to find a scaffold with pores in the
shape of a Schwartz primitive structure, resulting in the maximum
permeability. They also combined bulk modulus and permeability
in a single objective function and tailored these two competing
properties in a multi-physics optimization problem [99]. Using a
similar density-based optimization method, scaffolds with elastic
tensors similar to those of natural bones were designed; and the
performance of these scaffolds in subsequent tissue ingrowth was
investigated [100]. It is found that bone remodeling is at its best
when the scaffold elastic tensor matches or is slightly higher than
the elastic properties of the host bone.
The last row in Fig. 3 shows the porous structures with the
maximum bulk and shear moduli, respectively, at a given porosity.
These unit cells were obtained using the Bi-directional Evolu-
tionary Structural Optimization (BESO) method [101e105], which
shows faster convergence and unambiguous material definition
[106e109]. The BESO method, which allows the material to be
added and removed simultaneously during the optimization pro-
cess, is an extension of the original evolutionary ESO method
proposed by Xie and Steven [87,88]. As shown in Fig. 3 on topology
optimization, various unit cells with maximal bulk modulus,
maximal shear modulus, prescribed stiffness ratios in three di-
rections, and functionally graded structures can be obtained
through the BESO method.
The second class of topology optimization methods, represented
by the level-set algorithm [110], focus on tracking phase bound-
aries. In the level-set method, the interfaces of two phases are
implicitly defined by the zero-level contour of a high-dimensional
level-set function. The level-set method provides an effective
technique to represent smooth boundaries and to control topology
changes [111]. A variational level-set technique for periodic mate-
rial design problems governed by NaviereStokes and Maxwell's
equations was developed to attain material with maximal perme-
ability [112]. Level-set topology optimization enables the no-slip
boundary condition of fluids in Stokes flow to be naturally satis-
fied [113]. Periodic structures of scaffolds with the maximal effec-
tive diffusivity aimed at providing an ideal environment for
nutrient transportation were studied by a level-set based optimi-
zation method [114].
There have been tremendous advances in recent years in the
area of using topology optimization techniques to design multi-
functional materials with periodic structures, as shown in a
comprehensive review by Cadman [115]. Several of these de-
velopments are directly related to the design of scaffolds. Both
stiffness and diffusive transport properties were considered by
Hollister [12,44] and Challis et al. [116]. Using topology optimiza-
tion, Hollister and co-workers also created an interbody fusion cage
for improved arthrodesis [117]. The outcomes of their research
were used in clinic to support bone regeneration for craniofacial
reconstruction [12].
 X. Wang et al. / Biomaterials 83 (2016) 127e141
3.2. Constraints in structural design for additive manufacturing
Although AM can theoretically produce structures in any shape,
the quality of the structures may vary significantly depending on
the design and fabrication parameters [118]. Therefore, it is
necessary to consider the processability of the designed parts
during the topological design process, including the constraints and
limitations of AM technologies. However, there is still limited
research on creating design guidelines to achieve this goal. Kranz
et al. [119] experimentally investigated the restrictions of Laser
Additive Manufacturing (LAM) of Ti6Al4V and presented a
comprehensive structured catalogue. In their research, restrictions
and recommendations were presented based on experimental
measurements of different characteristics such as cavities (powder
removal, volume reduction), walls (edges, corners and thickness),
bores (size, orientation and tooling), gap (dimension, form), hollow
cylinder, overhangs and support structures. They also found that
the quality of AM parts was highly dependent on the materials,
machines and process parameters. Therefore, similar guidelines
could be achieved through similar methodology on different ma-
terial systems. Among many parameters, frequently discussed one
includes overhanging structures, which may lead to some unde-
sirable defects [120,121]. In an AM process, the overhanging
structure is not supported by solidified section or bottom substrate
when it is being built. Therefore, the overhanging structure is
strongly influenced by the orientation of building (Fig. 4 (a)-(d))
[121]. Therefore, the critical fabrication angle is of great importance
since it determines the form of overhanging structure, hence the
processability [120]. Fig. 4 (e) [120] shows the sketch of a circular
pore with overhanging arc AB, which can be processable if the
fabrication angle were larger than the critical value qc. Otherwise,
supporting structures have to be used, which are normally avoided
to prevent damage of parts in post-processing. A better choice in
design is to adopt structures with special geometrical arrangement
such as an octahedral lattice, whose lateral schematic is shown in
Fig. 4 (f) [120]. When the downward sloping surface CD has a larger
fabrication angle than the critical angle qc, no supporting structures
Fig. 4. Examples of overhanging structures: (a)e(c) structures having downward sloping face and (d) adjusting downward sloping faces by changing the orientation of the part, (e)
processability of a circular pore and (f) improved design of a pore. Images reproduced from Refs. [120,121].
133
are required.
There were also attempts to design structures so that they could
be fabricated using AM without support [122]. This approach is
interesting and useful, but may not be generally applicable to
scaffold designs. Other researchers examined the suitability of us-
ing SIMP and BESO topology optimization algorithms to design
structures for AM [123].
4. Current status of AM and topology optimization in
producing porous metallic structures
AM technologies are superior to conventional fabrication tech-
niques for producing porous metallic implants with complex and
customized structures, as shown in Fig. 5. In addition to the geo-
metric flexibility, composites with two or more phases can be
manufactured. These advantages enable AM to become a promising
tool for the production of biomedical implant devices, controlled
drug delivery systems, and engineered tissues [124e135]. Examples
include artificial joints and load-bearing implants produced by AM
using biocompatible materials such as hydroxyapatite, Ti, Ta and
CoeCreMo alloys [2,44,127,134] and customized prostheses such as
intervertebral spacers [135]. There has been growing research in-
terest in using topology optimization to design bone scaffolds and
orthopaedic implants [75,96e100,136e144], however significant
challenges still remain before these concepts could be used in
clinical practice. An important issue that may not be neglected
when applying topology optimization to scaffold design is to
consider the differences in physical, chemical and mechanical
properties of base materials produced by AM and conventional
fabrication techniques. The material property in AM process may
greatly affect the final topological shape of scaffold, which may
differ from the original CAD model obtained from topology opti-
mization. Moreover, good understanding of the change in me-
chanical properties in AM process may assist more accurate optimal
design in topology optimization procedure. This section will review
the status of research on AM fabrication of three main families of
alloys and the application of topology optimization.
134 X. Wang et al. / Biomaterials 83 (2016) 127e141
Fig. 5. Photographs of additive manufactured bone scaffolds: Ti6Al4V implants in sheep cervical spine (a) [135] NiTi scaffold for pseudoelastic applications (b) [161]; biodegradable
Mg stent after expansion (c) [162]; as-produced plain Ti scaffold (d) and the scaffolds with homogeneous and thick CaP coatings (e), (f) [152]; as produced Ti6Al4V scaffold (g),
scaffold after HCl etching treatment (h) and the corresponding enlarged view (i) [18].
4.1. Biocompatible Ti alloys
Metals in biological systems may experience corrosion and
release ions, which may result in many adverse physiological ef-
fects [4,145]. Therefore, the biocompatibility (defined by the
toxicity and carcinogenicity from the release of metal ions) of any
implant must be quantified to decrease the patient's risk and the
failure of the implantation [4]. The cytotoxicity of typical surgical
implant alloys and pure metals have been broadly studied in the
past decades [146e149]. It is now commonly accepted that vana-
dium (V) may cause sterile abscess and aluminium (Al) may cause
scar tissue, whereas titanium (Ti), zirconium (Zr), niobium (Nb) and
tantalum (Ta) exhibit excellent biocompatibility [4].
Another important motivation behind the design of biocom-
patible Ti alloys is the opportunity to decrease the modulus of Ti
alloys by adding b-stabilizing elements. As mentioned above, the b-
stabilizing elements should be biocompatible. Various b-type Ti
alloys composed of low modulus biocompatible elements (i.e., Ta,
Nb, Zr, Mo) were developed. These alloys exhibited lower modulus
than the commonly used Ti6Al4V. One example is Ti13Nb13Zr
[146], which showed improved bone biocompatibility and a
modulus of 79 GPa. Other b-type Ti alloys which exhibited lower
modulus (~55e65 GPa) included Ti29Nb13Ta4.6Zr [147] and
Ti35Nb5Ta7Zr [149].
In recent years, AM produced porous Ti alloy scaffolds were
widely reported with Ti6Al4V in dominance, such as the Ti6Al4V
implants in sheep cervical spine in Fig. 5 (a) [135]. Ryan et al. [150]
combined the multi-stage AM technology with the powder met-
allurgy process to produce porous Ti alloy scaffolds using wax
templates generated by CAD. The pore size of their designs ranged
from 200 to 400 mm and the porosity reached 66.8%. This method
could achieve controlled porous structure and ensure high reso-
lution in manufacturing. The resulting microstructure and surface
roughness were similar to parts manufactured by conventional
methods. This method could also be extended to the fabrication of
other metallic structures which are difficult to be directly made by
AM. Murr et al. [14] manufactured different porous Ti6Al4V im-
plants using AM based on micro-CT scan and CAD models built by
Materialise software. They studied the influence of geometric fea-
tures of unit cells on the mechanical properties of the porous
structures and found that when the porosity changed from 59% to
88%, the elastic modulus decreased from 3.03 to 0.58 GPa, which
proved that the elastic modulus of porous metals could be readily
adjusted through the porosity. Similarly Pattanyak et al. [17] stud-
ied porous Ti implants based on micro-CT scan on human cancel-
lous bones, which focused on structures with complicated internal
structures for bone ingrowth applications. The implants were
manufactured via SLM using Ti powder of less than 45 mm in size.
They found that the compressive strength decreased from 120 to
35 MPa when the porosity changed from 55% to 75%. Hollander
et al. [151] produced a variety of Ti6Al4V implants, ranging from
porous cylinder to solid human vertebra model with irregular
shapes.
Porous Ti6Al4V structures were shown to be effective in
 X. Wang et al. / Biomaterials 83 (2016) 127e141
supporting cell growth and new bone tissue growth, and cell based
study suggested that Ti6Al4V possesses high cyto-biocompatibility
[55,152e156]. In vitro studies were performed with porous Ti6Al4V
structures. Cell spreading and proliferation were observed across
the entire surface and inside the porous structure [156]. A similar
study was performed by Van Bael et al. [155], which suggested that
enhanced cell seeding and proliferation were achieved on porous
structures. Porous Ti6Al4V scaffolds were found performing well in
animal models since induced new bone growth and osseointegra-
tion were achieved on both bare and surface-coated porous Ti6Al4V
structures [135,152]. Although porous Ti6Al4V had been widely
studied, the potential release of toxic ions led researchers towards
looking for safer alternative alloys. Therefore, Ti alloys such as
Ti24Nb4Zr8Sn, Ti7.5Mo and Ti40Nb were designed and fabricated
by AM, which exhibited comparable mechanical properties to their
counterparts by conventional manufacturing approaches
[157e160].
There was significant research interest in using topology opti-
mization for the design of porous Ti alloy scaffolds [116,136e144].
While early works mainly focused on the theoretical consideration
of the structural design of the unit cells, recent efforts put more
emphasis on integrating topology optimization (the design aspect)
with AM (the fabrication aspect), e.g. Refs. [116,136].
4.2. Shape memory alloys
Shape Memory Alloys (SMA) are capable of regaining their
original shape after severe deformations when stimulated by
external environments [163,164]. Due to this unique property,
SMAs have found their way in orthopaedic implant applications.
Typical SMAs include NiTi or nitinol which normally contains
approximately 50 at% Ni and 50 at% Ti. The shape memory effect in
NiTi comes from the austenite/martensite phase transformation
since martensite is a low temperature stable phase with the
absence of stress whereas austenite is a high temperature stable
phase [165,166]. Currently, more than 90% of all commercial SMAs
are based on NiTi and its ternary alloys - NiTiCu and NiTiNb [167].
Solid NiTi has a modulus of 48 GPa, which is much lower than other
Ti alloys. Furthermore, NiTi allows for relatively large reversible
deformation of up to 8%. NiTi has higher stiffness than bone under
tendon, and is able to deform over a large strain range at an almost
constant stress (plateau stress) [161,168]. Due to these character-
istics, NiTi has been widely used in medical devices, such as surgical
tools, stents, orthodontic wires, plates and staples for bone frac-
tures. A NiTi scaffold for pseudoelastic application is shown in Fig. 5
(b) [161]. Main attractive features of SMAs are: (1) capability to
recover the original shape after large deformation (pseudo-elas-
ticity), (2) capability to recover the original shape from a stable
deformed shape when heated (shape memory effect) and (3) a high
damping capacity.
For biomedical applications, the presence of Ni in NiTi has been
a continuous concern since Ni is one of the highest sensitivities in
metallic allergy tests [169,170]. Therefore, attempts were made
either to develop surface modification techniques or to use sub-
stitution elements to mitigate this effect without sacrificing the
biocompatibility [160,171e175]. For example, TiNb and the related
TiNbX system (where X ¼ Zr, Ta, Hf) were developed which
exhibited elastic strains as high as 4.2% [175].
Common methods for making porous NiTi structures are based
on powder metallurgy (PM) and self-propagating high temperature
synthesis (SHS) of a mixture of elemental powders (Ni and Ti) or
pre-alloyed NiTi powder with space holding materials [176e178].
After removing space holding materials at relatively low tempera-
ture, the structures are further sintered at high temperature
[176e178]. Due to high reactivity of Ti and Ni, the sintering of
135
porous structures is normally done in high vacuum. However, these
methods have difficulties in precisely controlling the porous
structures of NiTi, i.e., pore size and pore shape. To overcome this
problem, AM technologies such as SLM have been used to produce
NiTi implants [179e184]. It was shown that AM produced NiTi parts
exhibited similar mechanical properties as those fabricated by
conventional methods such as casting [181,182].
In contrary to the substantial research on Ti alloys, no reports on
the application of topology optimization in the design of SMA
scaffolds involving AM fabrication can be found in the literature up
to date.
4.3. Biodegradable metals
Biodegradable materials, including both polymer-based and
metal-based ones, are used for some medical implants which will
gradually degrade in human body over a period of time [185]. In
some clinical cases, biomaterials are only needed temporarily in the
body and are expected to support the healing process and to
disappear after the healing process is completed. Fig. 5 (c) shows a
biodegradable Mg stent after expansion [162]. Compared to
polymer-based materials, biodegradable metals have higher stiff-
ness and strength, and are more suitable for load bearing condi-
tions. As the degradable alloys (mainly magnesium and iron based
alloys) are expected to degrade inside human body, the main
compositions of the alloys should be metallic elements that can be
metabolized, and demonstrate appropriate degradation rates in the
human body [186]. Due to its unique characteristics, Mg alloys were
used to manufacture cardiovascular stents [162] and bone screws
[187]. The degradable magnesium alloy bone screws were found
clinically equivalent to the conventional Ti screws; and no foreign
body reaction, osteolysis, or systemic inflammatory reaction were
observed for the Mg alloy screws [187].
A key parameter that needs to be considered in designing a
biodegradable metallic implant is its degradation rate in human
body. Pure Mg is known to have a fast degradation in high chloride
physiological environment but it may produce hydrogen gas at a
high rate from corrosion, which cannot be dealt with by the host
tissue. Fe-based biodegradable materials are known to exhibit a
slow degradation rate. Animal tests showed that large portions of
the pure Fe stent remained intact in the blood vessels 12 months
post-surgery [188]. Alloying is a typical method to adjust the
degradation rate of a metal. For instance, by adding elements such
as Y, Sr, Zn, Zr and Ca, Mg alloys were shown to have much lower
degradation rates in comparison with pure Mg. Such alloys also
exhibited high strength, which is desirable for load-bearing appli-
cations. In addition to alloying, amorphous structures like metallic
glass alloys MgZnCa showed low degradation rate and high
strength [189,190]. However, metallic glass alloys are generally
difficult to manufacture, which would add the cost to the applica-
tion of this type of material [190].
Porous Mg alloy implants were investigated as temporary bone
replacements in an animal model [191,192]. They were shown to be
able to enhance bone remodelling and appropriate host response.
However, porous Mg alloys degrade too rapidly in vivo, which may
leave subcutaneous gas cavities [193]. Since an open porous
implant has large surface area, only alloys with slow degradation
rate should be considered for making the porous structure, e.g. Mg-
4 wt.% Y. The element yttrium helps promote grain refinement, thus
resulting in a slow degradation and sufficient cyto-compatibility
[193]. Nguyen et al. [194] manufactured porous Mg alloys using
SLM and suggested that the dimension, surface morphology and
the oxygen pick-up of the laser-melted Mg were strongly depen-
dent on the laser processing parameters. Due to the high evapo-
ration rate at elevated temperatures, few attempts were made to
136 X. Wang et al. / Biomaterials 83 (2016) 127e141
fabricate Mg scaffolds directly using AM [195]. Instead, a technique
combining 3D printing and gravity casting was shown to be effec-
tive in producing topologically-ordered porous Mg structures
[196,197], where a porous NaCl mould was created using SLM and
then Mg alloy was cast into the mould. After removing the NaCl,
porous Mg structure with porosity of 41% and pore size of 1 mm
was obtained. The compressive strength of the porous Mg was re-
ported to be 13 MPa, which is comparable to porous Mg produced
by powder metallurgy [197].
A review on porous biodegradable metals for hard tissue scaf-
folds can be found in Ref. [198]. A theoretical study of topological
design of polymeric scaffolds considering the effect of biodegra-
dation was conducted by Chen et al. [199]. No reports on the
application of topology optimization in the design of biodegradable
metallic scaffolds involving AM fabrication have appeared in the
literature so far.
5. Heat-treatment and surface modification of porous
metallic structures produced by AM
5.1. Heat-treatment
The mechanical properties of AM produced materials depend
heavily on the processing parameters, including building layer
thickness, scan speed, energy density and focal offset distance
[200,201]. Usually AM (SLM or EBM) produced materials have
relatively high yield stress (Ti6Al4V, ~1000 MPa) and ultimate
tensile strength (Ti6Al4V, ~1150 MPa), but a relatively low ductility
(Ti6Al4V, less than 10%) [200,202,203]. In order to improve the
mechanical properties of AM produced porous biomaterials so that
they can mimic the human tissues and fulfil the desired functions,
post-treatment is of critical importance. It is known that the mi-
crostructures of as-built materials by AM are very different from
those by traditional casting or forging approaches. AM is a layer-
wise build-up process with high cooling rates that lead to signifi-
cant internal thermal stresses in the structure. During the building
process, the scanning by either a laser (for SLM) or an electron
beam (for EBM) may cause the instabilities of the melt pool,
resulting in increased porosity and high surface roughness
[200,204]. Therefore, heat-treatment for changing the microstruc-
tures is routinely applied in most applications to meet the product
requirements. The post-treatment process also enables the reduc-
tion of thermal stresses in AM produced structures. For Ti6Al4V,
post heat-treatment is typically performed within the a þ b region
(where a to b phase transition temperature Tb is 995  C), which can
control the morphology and size of the a-phase without signifi-
cantly influencing the prior-b grain size. Heat-treatment above Tb
leads to a complete dissolution of the a phase and the coarsening of
prior-b grains [200]. A proper heat-treatment process may sub-
stantially improve the mechanical properties of AM produced
materials. Thone et al. [205] observed significant improvement in
ductility and fatigue strength after heat-treatment of SLM produced
Ti6Al4V. They revealed that the tensile strength of heat-treated
Ti6Al4V slightly decreased from 1080 MPa to 945 MPa but the
elongation at failure increased significantly from 1.6% to 11.6%,
along with remarkably prolonged fatigue life of parts from 28,900
to 290,000 cycles [205]. The improvements in the mechanical
properties after post heat-treatment are mainly due to the elimi-
nation of thermal stresses and the changes of microstructures. On
the other hand, an adequate selection of AM processing variables
can facilitate in-situ heat treatment. The microstructure of Ti6Al4V
made by SLM is often dominated by a0 martensite due to rapid
cooling, which can be decomposed to lamellar a þ b structure
during SLM process by tuning the processing variables [201]. After
the optimization of processing conditions, Xu et al. [201] produced
Ti6Al4V with comparable or better mechanical properties than
forged Ti6Al4V.
5.2. Surface modification
Surface modification plays an important role in enhancing the
biological performance of AM produced porous biomaterials,
particularly bioactivity and biocompatibility [206e212]. Ti alloys
are normally covered by one layer of 3e7 nm thick native oxide,
namely TiO2, which provides excellent chemical inertness, corro-
sion resistance and biocompatibility. In the human body, Ti alloy
implants may experience non-specific protein adsorption and
interrogation of neutrophils and macrophages, which may attract
fibroblasts to an encapsulation process. To ensure an effective
biological bond between Ti alloy implants and surrounding bones,
surface modification is essential to improve the conductivity of
bones or the bioactivity of titanium [7,213]. The surface
morphology of Ti alloy implants depends on the history of material
processing. For AM produced porous Ti alloys, powders tend to
become small liquid spheres when heated up by laser or electron
beams [18]. Such a “balling” effect is a complex metallurgical pro-
cess that leads to a rough surface and residual powder particles
[179]. These loosely connected powder particles can be removed
through blasting or other post-processing methods before
implantation.
Surface modification or activation of Ti surface can be achieved
by various techniques such as plasma spray, physical or chemical
vapour deposition, ion implantation, electrochemical oxidation,
acidic or alkali etching, solegel, heat-treatment, and surface
machining or grinding. For porous metallic structures, there are
two main approaches, based on surface coating and surface
corrosion.
A popular coating-based method is solegel process, which is a
simple yet versatile method for creating oxide coatings at relatively
low temperatures. For implants with a complex topology, dip
coating is normally used. The solegel process may deposit thin
(<10 mm) inorganic coatings. The chemical composition and mi-
crostructures of the coating can be better controlled by the solegel
process than by other methods. Other advantages of the solegel
process include homogeneity and low cost. Brie et al. [214] used
solegel to form a bioceramic coating (CaP) on porous Ti6Al7Nb
implants. The coating uniformly covered the external and internal
surfaces of the implants; and the coated porous structures exhibi-
ted improved biocompatibility. Other methods include electrolytic
deposition (ED) and plasma spray. ED can produce CaP coatings
having a thickness of a few microns to several hundred microns,
which can be controlled by applying appropriate current density
and processing time [152]. This may also assist to control the sur-
face morphology of CaP coatings from needle-like to plate-like
structures. Coating through ED can produce uniformly and fully
covered surface, which makes it suitable for functionalizing porous
structures. Chai et al. [152] found that the bioactivity of the CaP
coated Ti6Al4V scaffold (surface morphology is shown in Fig. 5 (d)
to (e)) was significantly improved and it was possible to produce
osteoinductive “bio-units” for the repair of bone defects.
Corrosion-based surface treatment involves interfacial chemical
reactions of structures in corrosive solution. Such chemical pro-
cesses include alkali treatment [215e217], acid etching [179] and
anodization treatments [218,219]. Fig. 5 (h) to (i) show the surface
morphology of scaffold before and after HCl etching treatment [18].
The chemical reaction may produce a thin oxide layer (of TiO2, for
example) on the surface of the metal, usually resulting in improved
bioactivity. The thickness of the active layer can be controlled from
tens of nanometer to hundreds of microns by adjusting processing
variables. Alkali treatment was initially introduced by Kim et al.
 X. Wang et al. / Biomaterials 83 (2016) 127e141
[215] to improve the bioactivity of Ti implants owing to a biologi-
cally active bone-like apatite layer on Ti surface. Anodization is a
mature electrochemical process capable of producing protective
layers on the metal surface with adjustable surface microstructure
and crystal structure [218,219]. Special care should be taken with
regard to the possible negative effect on mechanical properties
after corrosion-based surface treatment. It was reported that alkali
treatment might result in the deterioration of mechanical strength
of porous Ti alloy scaffolds and also cause the embrittlement of the
struts in the scaffolds [209].
6. Challenges and future directions
Additive manufacturing provides unprecedented opportunities
for producing customized medical implants as this technology can
fabricate structures of complex external shapes and intricate in-
ternal architectures. Topology optimization has become a powerful
digital tool for the design of optimal structures and materials. The
integration of these two technologies sees a promising future in
designing and manufacturing biocompatible orthopaedic implants
with desired mechanical properties and minimal side effects on
patients in clinical applications. Key challenges and future di-
rections in integrating the two technologies are as follows:
i) A comprehensive and reliable database containing detailed
information on the mechanical and biological properties of
human bones is yet to be established. This database should
include properties of bones for different age, gender groups
and at different locations. Such information is required as the
design “target” of the topology optimization process.
ii) Sophisticated topology optimization algorithms capable of
dealing with multi-functional designs on multiple length
scales simultaneously needs to be developed. Preliminary
studies along this line can be found in Refs. [220,221].
iii) Topological design of the lattice structures that can be easily
produced by AM and exhibit anisotropic mechanical prop-
erties similar to human bones is another promising direction,
despite that the fact that there has been extensive research
on topology optimization based on continuum models.
iv) Constraints and limitations of current AM technologies, such
as the critical angle of the overhanging structure and the
difficulty in removing the supporting structure, should be
involved in newly-developed topology optimization algo-
rithms so that the “optimized” designs could actually be
fabricated by AM.
v) The long-term in vivo material/biological performance of
porous metallic implants that are designed through topology
optimization techniques and produced by AM needs to be
rigorously assessed in order to ascertain the advantages and
drawbacks of such implants.
vi) Novel alloying systems capable of enhancing the mechanical
and biological performance of porous metallic implants are
in great demand, together with new post-treatment tech-
nologies for improving the bioactivity and biocompatibility.
7. Conclusions
In this paper, the current status of the topological design of
porous metallic implants and the fabrication of such implants using
additive manufacturing is reviewed. First the mechanical proper-
ties of human bones are discussed. Then it is demonstrated that
topology optimization is a powerful digital tool that can be used to
obtain optimal internal architectures for porous implants which
not only satisfy multifunctional requirements but also mimic
137
human bones. Furthermore it is shown that additive manufacturing
is the most promising and disruptive technology in the fabrication
of porous orthopaedic implants designed through topology opti-
mization. To further improve the mechanical and biological per-
formance of these structures, both post-treatment and surface
modification are necessary. Based on these discussions, challenges
and future directions of the integration topology optimization with
additive manufacturing are identified. This review provides useful
information to researchers and practitioners who are working in
various areas of the truly multidisciplinary topic of bone implant
design and fabrication.
Acknowledgements
This work was supported by the Australian Research Council
(DP140100213 and LP140100607).
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