Materials Science and Engineering C 76 (2017) 1328–1343

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Materials Science and Engineering C

journal homepage: www.elsevier.com/locate/msec

Review

Metallic powder-bed based 3D printing of cellular scaffolds for

orthopaedic implants: A state-of-the-art review on manufacturing,
topological design, mechanical properties and biocompatibility
X.P. Tan ⁎,1, Y.J. Tan 1, C.S.L. Chow, S.B. Tor, W.Y. Yeong
Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore

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

Article history: Metallic cellular scaffold is one of the best choices for orthopaedic implants as a replacement of human body
Received 28 September 2016 parts, which could improve life quality and increase longevity for the people needed. Unlike conventional
Accepted 21 February 2017 methods of making cellular scaffolds, three-dimensional (3D) printing or additive manufacturing opens up
Available online 24 February 2017
new possibilities to fabricate those customisable intricate designs with highly interconnected pores. In the past
decade, metallic powder-bed based 3D printing methods emerged and the techniques are becoming increasingly
Keywords:
3D printing
mature recently, where selective laser melting (SLM) and selective electron beam melting (SEBM) are the two
Cellular scaffolds representatives. Due to the advantages of good dimensional accuracy, high build resolution, clean build environ-
Titanium ment, saving materials, high customisability, etc., SLM and SEBM show huge potential in direct customisable
Implant manufacturing of metallic cellular scaffolds for orthopaedic implants. Ti-6Al-4 V to date is still considered to be
Topology the optimal materials for producing orthopaedic implants due to its best combination of biocompatibility, corro-
Biocompatibility sion resistance and mechanical properties. This paper presents a state-of-the-art overview mainly on
manufacturing, topological design, mechanical properties and biocompatibility of cellular Ti-6Al-4V scaffolds
via SLM and SEBM methods. Current manufacturing limitations, topological shortcomings, uncertainty of bio-
compatible test were sufficiently discussed herein. Future perspectives and recommendations were given at
the end.
© 2017 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1329
2. Metallic 3D printing systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1329
2.1. Selective laser melting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1330
2.2. Selective electron beam melting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1330
3. Hierarchical designs for metallic cellular scaffolds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1330
3.1. Topological design of cellular structures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1331
3.1.1. Stochastic and reticulated cellular scaffolds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1331
3.1.2. Bend- and stretch-dominated unit cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1333
3.2. Feasible scaffold design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1333
4. Microstructure and mechanical properties of metallic cellular scaffolds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1334
4.1. Microstructure of cellular Ti-6Al-4V struts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1334
4.2. Compressive properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1334
5. In vitro and in vivo tests for orthopaedic implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1337
5.1. In vitro studies: cell attachment, proliferation and occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1338
5.2. In vivo studies: bone regeneration and ingrowth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1338

⁎ Corresponding author.
E-mail address: [email protected] (X.P. Tan).
1
The first two authors contribute equally to this paper.

http://dx.doi.org/10.1016/j.msec.2017.02.094
0928-4931/© 2017 Elsevier B.V. All rights reserved.
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1329

5.3. Scaffold designs favouring cell ingrowth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1340

6. Concluding remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1340
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1341

1. Introduction bone [19]. Another crucial reason to use cellular structures is to mimic
the structure of native bone to promote bone regeneration and in-
Manufacturing places broad emphasis on speed, accuracy, flexibility, growth into the implant, which has so far not been observed on solid
and minimizing waste nowadays. This is why there have been increas- structures [20,21]. Studies have also shown that the surface types of
ing interests in the area of additive manufacturing, most commonly these implants play a role in regulating bone cell responses and bone
known as three-dimensional (3D) printing. While conventional healing [22]. Rough surfaces obtained through sandblasting and/or
manufacturing methods such as machining are rooted in removal of acid-etching are favoured [23]. Chemically modified implant surface
material from bulk form (i.e. subtractive manufacturing), the essence by using hydrogen chloride (HCl) and sodium hydroxide (NaOH) also
of 3D printing is to build up an object layer by layer adding material believed to provide a better fixation of the implant and improve the
only where necessary [1,2]. Near-net-shape capability, or printing long-term stability of the implant [24].
parts close to the designed profile, with the exception of support struc- In general, it is very difficult or impossible to rely on traditional
tures, uses as little excess material as possible. This drastically reduces manufacturing methods to craft a cellular structure throughout an or-
by-product waste as compared to subtractive manufacturing. This in thopaedic implant. 3D printing makes this relatively easy as it is builds
turn reduces the lead-time and tooling required for product completion, up a form layer by layer, including the internal cellular cross-sections.
leading to savings in production costs [3]. The capability of 3D printing It is hence possible to produce intricate cellular implants tailored to
extends to cover a wide range of material types, including polymers, ce- biomedical applications. To produce a useful implant, factors such as
ramics, metals, etc. [4,5]. topological design of pores, porosity, mechanical properties, and
One mainstream direction for 3D printing is that of biomedical appli- interfacing with natural bone have to be carefully considered [25]. De-
cations, specifically in creating scaffolds for medical implants [6–10]. sign of cellular scaffolds can also be made more anatomically-suitable
This paper focuses on the fabrication of scaffolds for orthopaedic by applying image data from medical databases. This allows satisfactory
(bone) implants by utilizing powder-bed based metallic 3D printing replication of natural bodily functions such as transport of nutrients and
[11]. The first and foremost requirement for the orthopaedic implants waste [12].
is to fill 3D defect cavities. Traditionally, metallic orthopaedic implants This review is divided into the following four major sections: metal-
have been produced by investment casting or forging. Although differ- lic powder-based 3D printing techniques, hierarchical design of metallic
ent prosthetic implant sizes can be produced through the conventional cellular scaffolds, microstructural characterization and mechanical
means, they cannot achieve the same level of patient-customization as properties, and in vitro and in vivo studies of 3D-printed cellular bone
3D printing. With 3D printing, the shape and design of implants can implants. This review will gather findings from across the fields related
be individualised to ensure best fit to their recipients. This can even be to 3D printing for bio-implants, and serve to compare the different
done by direct data input from computed tomography (CT) or magnetic methodologies used to eventually arrive at the most reasonable direc-
resonance imaging (MRI) scans. Beyond efficiency, the near-net-shape tion for each of the above sections. In the first section, the working prin-
capability of 3D printing drastically reduces wastage of material as com- ciples behind two common powder-based 3D printing techniques,
pared to traditional subtractive manufacturing methods. This will help selective laser melting (SLM) and selective electron beam melting
to balance out the equipment setup costs in the long run [12]. (SEBM), will be examined and compared. These methods involve
Hutmacher derived four essential characteristics of a biodegradable using a high energy beam to melt the shape of cross-sections into layers
bone scaffold, which were found to be transferrable to a metallic ortho- of metallic powder, building layer upon layer into the desired product
paedic implant as well: (i) biocompatibility leading to a natural cell [26,27]. The advantages and disadvantages of each method with regards
growth rate on the scaffold; (ii) similar mechanical characteristics to biomedical applications will also be mentioned. The next section will
with existing tissue at implant area; (iii) suitable porosity for cell in- briefly touch on the needs for metallic scaffold implants and present
growth and channels for nutrient and waste transportation; (iv) attrac- regular and irregular interconnected pore cellular designs. This will
tive surface morphology for cell attachment and proliferation [13]. lead up to the following section which will present the mechanical be-
Biocompatibility of a scaffold mainly depends on the materials used haviour obtained from testing entire cellular structures. A study into
and the fabrication process. Titanium and its alloys, and various other the microstructures of these 3D printed cellular structures will be
metals, such as cobalt chromium (CoCr) alloys and stainless steel 316L made and the differences resulting from different manufacturing pro-
(SS316L), are known to have excellent biocompatibility [14]. While cesses will be compared. The final section will look at the performances
this review will be focused on titanium alloys, which were most widely of 3D-printed bio-implants with regard to in vitro cell culture and
used for orthopaedic implants because they have a lower modulus of in vivo animal testing. Challenges and future perspectives on 3D-
elasticity that is closer to that of host bone and are more biocompatible printed cellular scaffolds for orthopaedic implants will be given in the
than CoCr alloy or SS316L. On the other hand, titanium alloys are notch- end.
sensitive, which predisposes it to cracks if the implant is not well
supported [15]. 2. Metallic 3D printing systems
In addition, it is important for an orthopaedic implant to mimic me-
chanical characteristics of bone to maximise its usefulness in the body. SLM and SEBM are the two prolific powder-bed based 3D printing
Dissimilar mechanical properties between the implant and bone may techniques for metals nowadays. In both processes, high energy
lead to many undesirable effects. One such phenomenon called stress beams are utilized to melt cross-sectional shapes into layers of metal
shielding is caused by the differences in elastic modulus or stiffness, powder [26,28], fusing powder particles into a large form, with each
leading to the existing bone being overly relieved of load [16]. This layer representing a “slice” of the final product. After every “slice” is
leads to bone resorption which may cause the implant to loosen from formed, the build platform moves downwards by the distance equiva-
the bone [17], which might affect the fixation and longevity of the im- lent to a layer's thickness and a fresh layer of metal powder is uniformly
plant within the body [18]. A solution to this is to use cellular or porous spread on top of it. The process repeats so that the cross-sections build
titanium structures, which have closer mechanical properties to actual up cumulatively until the build is finished. At the end, the excess,
1330 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343

unmelted powder is removed by high-pressure blowing, leaving 2.2. Selective electron beam melting
behind the near-net-shape build as defined in the computer-aided
design (CAD) model [29]. The unused powder can be recycled for SEBM technique was developed by a Sweden-based company Arcam
subsequent rounds of fabrication. Both processes are capable of AB, who named their commercial machine electron beam melting
fabricating complex designs such as cellular structures with high (EBM). Similar to SLM, EBM involves a system consisting of powder
accuracy [30]. hoppers, rake, build platform, and an energy source used to melt pow-
The main difference between SLM and SEBM is the power source - der. However, EBM adopts an electron beam as the energy source. Elec-
SEBM utilizes electron beams while SLM employs laser beams [31]. trons emitted by a tungsten filament are accelerated by a high voltage of
This leads to a difference in operating environment as it is necessary 60 kV to a high velocity before being focused into a high energy beam by
to use a high vacuum in SEBM to maintain the strength of the electron electromagnetic lenses [37]. Unlike SLM, EBM must work under a high
beam. Metallic powder-based 3D printing, specifically SEBM, has vacuum due to some inherent features of electron beams. Additionally,
proved to be advantageous in manufacturing complex cellular titanium certain metals or alloys, being highly reactive, are susceptible to gather-
builds suitable as bio-implants. Titanium, being an extremely reactive ing impurities when exposed to air. Impurities afflicted by contact with
metal, is highly susceptible to the formation of impurities simply oxygen or other chemical entities in air can be prevented using a vacu-
through contact with molecules of oxygen, nitrogen, and other um chamber and this way, the integrity of a 3D printed titanium part
atmospheric gases. Such impurities increase the difficulty of can be ensured [38]. As with SLM, there is a strong correlation between
manufacturing these titanium parts to meet the mechanical properties powder quality and the fabrication process. A good powder for metal
required of an implant, for example unsatisfactory ductility. The integri- printing is defined by good flowability, compactness of packing, and
ty of titanium implants can be preserved under the high vacuum of the heat transfer characteristics, all of which can be maximized by using
SEBM process. Another benefit of 3D printing is the high flexibility of its fine powder with spherical morphology. Powder size distribution
builds. Various properties, such as porosity, strength, and ductility, can must also be taken into consideration as this can have a strong effect
be adjusted to achieve the optimum in replicating the function of on build density, surface finish, and mechanical characteristics [39].
bone in a body [32]. Table 1 lists the main differences between SLM and SEBM tech-
niques. As compared to SLM, SEBM is faster in producing fully dense
builds with a high energy electron beam allowing full melting of powder
2.1. Selective laser melting particles and a faster scanning speed. Completely molten particles are
also key to aid metallurgical bonding between layers [38]. SEBM is
The set-up of an SLM system consists of a laser source, powder con- also the preferred method to fabricate Ti-6Al-4 V as interstitial elements
tainers and delivering and layering apparatus, build platform, and com- can be minimized due to the highly clean environment [40].
puter systems for process parameter controls [33]. The build platform is
heated to a temperature usually below ~200 °C and maintained at this
temperature throughout the process. The desired metal or alloy in pow- 3. Hierarchical designs for metallic cellular scaffolds
der form is loaded into a tank. This powder, of mean particle size rang-
ing between ~ 20–60 μm, is delivered onto the build platform, and Patients with joint damage, such as hip or knee joint, that causes
recoated into layers with the thickness of a few powder particles, typi- pain and interferes with daily activities despite treatment may be candi-
cally 30–100 μm [34]. A flat, even layer is crucial to the accuracy and re- dates for a replacement surgery (arthroplasty). Osteoarthritis, or degen-
liability of the SLM process and hence, the morphology and erative joint disease, is the most common reason for the total hip or
granulometry of powders used must be scrutinized. This is to ensure knee arthroplasty. Arthroplasty is a surgical procedure in which the dis-
that powder particles are able to be spread effectively and uniformly eased parts of the joint are removed and replaced with artificial parts
at operating temperatures to make up the desired thickness. As a result, (prosthesis). The goals of arthroplasty include increasing mobility, im-
metal powders produced for SLM and other powder-based 3D printing proving the function of the joint, and relieving pain. The history of the
processes should ideally possess good sphericity and small size distribu- different prostheses and arthroplasty procedures were reviewed in
tion range to enhance their overall flowability [35]. Additionally, oxygen Learmonth et al. [15].
must be removed from the system to prevent oxidation. This is usually Cement-free implants were designed to provide adequate initial sta-
achieved by introducing either purified argon or nitrogen into the bility and to encourage bone to osseointegrate onto or into the implant.
build chamber [36]. After all the above conditions have been met, a Most of the bone tissues are composed of a porous environment [43,44].
laser beam is focused onto the powder bed, tracing the areas to be Hence, in the conventional cement-free implants, their surfaces must be
melted. To achieve an optimal effect depending on the powder material further processed to provide a sturdy fixation. This is done by applica-
and build specifications, various laser parameters can be altered. A vari- tion of porous coatings such as sintered beads, fibre mesh or thermal
ety of lasers can be used such as CO2, Nd: YAG, and fibre lasers. These spray processes [45] that would allow bone ingrowth to fix the implant
vary in wavelength and energy density, and may have different levels in place. Results showed sufficient bone ingrowth. However, many of
of absorptivity with different materials [33]. The laser power, scanning these designs were associated with a high rate of stress-shielding and
speed, and hatching pattern could be optimised in order to achieve a bone loss. Patients occasionally complained about thigh pain, presum-
specific build definition [30]. ably due to elastic mismatch between the rigid implant and the biolog-
These processes and apparatus are similar to that used in selective ically flexible bone tissue [15]. Concluding the clinical related outcomes,
laser sintering (SLS), another commonly used rapid prototyping meth- orthopaedic implants must be able to withstand regular loading but
od, although the parameters set may differ. While SLS has been a com- have mechanical properties that match the stiffness of the local host
monly used method in rapid prototyping for polymers and metals, bone to reduce bone resorption induced by stress shielding. This can
there has been a shift in preference towards SLM over the years. Unlike be done by having cellular designs that decrease the stiffness and in-
SLS, SLM allows full melting and solidification of metal powder to pro- crease the implant's surface area that encourages bone ingrowth [46,
duce components with density and mechanical properties comparable 47]. Effective permeability is determined by the presence of intercon-
to that of bulk material. This way, benefits of manufacturing with bulk nected pores, the 3D pore arrangement and the porosity [12] in the im-
material such as strength can be obtained without the material waste plant. High permeability assists in transportation of cellular nutritional
and lead-time consumption associated with traditional subtractive and waste matter, and allows for bone ingrowth, leading to a sturdier
manufacturing methods [33]. Accordingly, more intricate and complex and longer-lasting fixation [48]. However, the requirements of strength
designs such as lattices become achievable. and permeability must be balanced because they both depend, in
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1331

Table 1
Comparison between SLM and SEBM processes.

SLM SEBM References

System schematic [28,41]

Power source Laser beam (up to 1 kW) Electron beam (3 kW) [40]
Operating environment – Inert gas environment – High vacuum [40]
– Preheat start plate up to 200 °C – Chamber temperature maintained at 600–1000 °C
Powder material Metals, polymers, ceramics, composites, etc. Metals and metallic-based composites [29]
Powder layer thickness 20–100 μm 50 μm [40]
Powder particle size ~ 20–63 μm ~ 45–105 μm [27,42]
Melting method – Contour melting – Powder bed preheating [40]
– Hatch melting – Contour melting
– Hatch melting
Build rate Slow Fast [40]

opposite ways, on the amount of material (and density of structures) this can be done through image- [50,51] or CAD-based [52–54]
that makes up the implant. methods. These archives can be tapped for designs to be agglomerated
Hierarchical objects contain structural elements which themselves into full scaffold architectures [12].
have structure [49]. A rigorous hierarchical design is required to maxi-
mise the functionality of implant in the body. Design of cellular struc-
3.1. Topological design of cellular structures
ture for orthopaedic implants includes a careful selection of the
materials, the cellular structure design, and the manufacturing process.
Cellular solids are composites in which one phase is solid and the
These design considerations can boost the affinity between bone tissues
other is empty/fluid [49]. The solid phase consists of a lattice, which is
and the implant surface which determines the effectiveness of bone
a connected network of struts. Cellular solids are characterized by a typ-
cells infiltration and bone ingrowth [12]. It is advisable to archive all
ical unit cell with certain symmetry elements [55]. The unit cell in
unit cells designed (including different sizes of the same design), and
millimetres or micrometres scales allows the cellular solids to be viewed
both as structures and as materials [55]. Hence, the macroscopic proper-
ties of cellular solids, such as the elastic moduli and compressive
strength, are governed by both material and structural properties [56].
Table 2
This review will only focus on designs with interconnected pores (i.e.
Collection of existing cellular designs [38,40,63,64], and [67–70]. Figures adapted and
reprinted from Ref. [38,40,63,64,67,68] and [70], with permissions from Elsevier. open cellular structures), as these designs allow transport of cells into
the implant [57–59]. Open cellular structures may originate from
CAD Imagery Physical Models
many different designs. These designs may also vary in porosity, pore
size, strut thickness, shape and orientation of unit cells, etc., to mimic
the macroscopic properties of actual human bone structure [7].
Open Forms

A large variety of cellular designs have been fabricated through 3D

printing techniques [60,61]. In light of growing interest in the area of
[63] [63,64]
3D-printed porous metallic orthopaedic implants, there has been an
enormous drive to optimise the structural design to (i) provide mechan-
ical properties similar to natural bone to minimise stress shielding; (ii)
to boost load-bearing ability; as well as (iii) to aid bone cell ingrowth
Archival Unit Cells

[38]. These can be achieved by carefully altering the design's porosity

(and gradient in porosity if applicable) and pore shape to create a strong
[67] [38,68] structure which encourages bone ingrowth [25]. In the multitude of dif-
ferent structure designs, there are a few guidelines for desired effects. In
general, the stiffness and strength of solids decrease with the increasing
porosity and in turn the permeability of solids is enhanced. Degradation
Vertical channels
in mechanical properties can be drastic with the decrease in strut size of
Functionally Graded Structure

Cylindrical
channels the cells [38]. When comparing between two pore shapes, e.g. spherical
Horizontal channels

vs. cylindrical, spherical pores were found to be stiffer while cylindrical

ones tend to be more permeable [12].
Honeycomb
[69,70] Honeycomb [40,69]
3.1.1. Stochastic and reticulated cellular scaffolds
Cellular designs can come in many forms, either stochastic (irregu-
lar) such as expanded foams, or reticulated (regular) such as lattice
structures or meshes with constantly repeating unit cells [62]. The
1332 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343

(a)

100 m

(b)

Fig. 1. Examples of cellular structure design in terms of cellular forms and their
deformation behaviour [65,72].

1 m
stochastic open cellular foams have pores of random shapes and sizes
and their unit cells do not repeat regularly. Open cellular foam struc-
tures were manufactured in Ti-6Al-4 V using a CAD model obtained
from CT-scanning existing aluminium alloy foams [63] or by inverting (c)
a scanned model of a container filled with spherical glass beads [64].
The stochastic foams' structure is often heterogeneous, causing the
foams to be strong in some regions, while weak in the others. The
weak regions drag down the mechanical performance significantly
[55]. Drastic degradation in mechanical behaviour in stochastic foams,
especially at relative densities less than 0.1%, shows a quadratic (or
higher order) scaling relationship between elasticity and density as
well as strength and density [65]. An improvement in mechanical prop- 50 m
erties can be attained from structures that contain unit cells arranged in
an ordered hierarchy [65].
Reticulated lattice is yet another variant of cellular structures. Unlike Fig. 3. (a) Optical and (b) transmission electron microscopy images showing strut
stochastic structure, it consists of repeating unit cells leading to a highly microstructure of a SEBM-fabricated Ti-6Al-4V mesh array. (c) An optical image
regular form. One method of designing a cellular scaffold to be 3D showing strut microstructure of a SLM-fabricated Ti-6Al-4V lattice structure [74,75].
printed involves choosing the unit cell design from an archive. To Figures adapted and reprinted from Ref. [74] and [75], with permissions from Elsevier.

date, many different unit cell designs have been produced and studied
and they vary from the most basic cube or triangular prism, to the extremely low density with a periodic microarchitecture. Nonetheless
more complex octagonal prisms or rhombic dodecahedrons [66]. 3D the design of these topologies is limited by the processing-related
printing technologies have accelerated cellular solid designs of restrictions. Table 2 compiles some typical cellular structures.

0.9 (a) 20 30
40
0.9 (b) 10 20 30

0.8 0.8 40
Strut thickness, t (mm)

Strut thickness, t (mm)

50
Cell size: a 50 Cell size: a
0.7 0.7 Porosity (%)
60 Porosity (%)
SEBM
0.6 0.6 60
70 SEBM
0.5 0.5 70
2.5 80
0.4 0.4 2.5 80
2
0.3 SLM 90 0.3 2
1.5 SLM 90
1.5
0.2 1 0.2
1
0.1 0.1
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8

Pore size, p (mm) Pore size, p (mm)

Fig. 2. Feasible design space (triangular shaded areas) and constraints for (a) tetrahedron and (b) octet truss cellular structure using SLM [25] and SEBM.
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1333

the cell struts [71]. Most of the cellular structures [71], especially the
stochastic foams [65], belong to the bend-dominated types. A bend-
dominated unit cell structure consists of b struts and j frictionless joints,
satisfying the Maxwell's criterion of M = b − 3j + 6 b 0. The cell struts
bend upon loading. A stretch-dominated unit cell structure satisfies the
Maxwell's criterion of M = b − 3j + 6 ≥ 0. In general, it is structurally
stronger than the bend-dominated type. The struts of stretch-
dominated cellular solids are loaded in tension or compression largely
without bending [56]. The stretch-dominated cellular solids show a lin-
ear scaling behaviour of the strength and the stiffness with the apparent
density [65]. Fully triangular 3D structures, such as the tetrahedral-truss
and octet-truss unit cell, belong to the stretch-dominated type. Design-
ing orthopaedic implants using stretch-dominated cellular structures
would allow both to exploit the topological advantages and to gain en-
hanced strength of materials [56]. Fig. 1 illustrates different cellular de-
signs from varying cellular forms and deformation behaviour as stated
above.

3.2. Feasible scaffold design

Arabnejad et al. [25] conceived a strategy to identify feasible design

limits for different lattice structures fabricated by SLM. It took into ac-
count the following constraints: (1) bone ingrowth requirements (i.e.
pore size and porosity) and (2) manufacturing limitations (i.e. strut
thickness), to encourage bone ingrowth. These requirements can be vi-
sually represented on a graph plotting strut thickness against pore size,
as shown in Fig. 2. Different porosities and unit cell sizes are represented
as diagonal lines in the graph. It is worth noting that different feasible
design graphs will be obtained varying unit cell topologies and
manufacturing techniques. By using tetrahedron and octet topologies
(two representative stretch-dominated unit cells) as examples, we
modify the graphs presenting the manufacturing limitations of both
SLM and SEBM processes, with minimum printable strut thicknesses
of 200 and 400 μm, respectively. For bone ingrowth, minimum porosity
of the scaffold should be at least 40% for sufficient cell infiltration [73],
Fig. 4. Plots of (a) relative modulus vs relative density and (b) relative strength vs relative and pore size should be within 50–800 μm for adequate permeability
density on logarithmic scales for different types of cellular solids [55].
[18], which will be discussed in detail in the following sections. The fea-
sible design space is defined as the triangular shaded areas which satisfy
all the above constraints [25]. Obviously, the feasible design space of
3.1.2. Bend- and stretch-dominated unit cells SLM is much bigger as compared to SEBM due to its thinner minimum
Cellular solids can be classified into bend- and stretch-dominated to- strut thickness. Moreover, stretch-dominated cellular structures will
pologies because they deform by either the bending or the stretching of usually have a relatively narrower design space in comparison to

Fig. 5. Plots of (a) modulus vs porosity and (b) maximum strength vs porosity for different types of cellular Ti-6Al-4V [18,19,24,25,64,82,85–92] and Ti-6Al-4 V ELI [62,68,91,93–99]
scaffolds.
1334 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343

Fig. 6. Ashby chart for different types of cellular Ti-6Al-4V scaffolds.

bend-dominated ones because they may have complicated diagonal at room temperature as well as stabilize the β phase [26]. The micro-
struts. structure of both SLM and SEBM-built Ti-6Al-4 V cellular struts consists
of columnar prior β grains and within these prior β grains, it was ob-
served to be dominated by α΄ thin platelets [74–76] as shown in Fig. 3.
4. Microstructure and mechanical properties of metallic cellular
Differently, due to the elevated build temperature involved in SEBM,
scaffolds
those α′ martensite could be partly decomposed into ductile α/β
dual-phase microstructure in some specific builds. It means that
4.1. Microstructure of cellular Ti-6Al-4V struts
SEBM-built cellular scaffolds may have better fracture toughness
when compare to the SLM-built counterparts. However, it is worth not-
Among all the biocompatible metallic materials such as CP-Ti, Ti al-
ing that the microstructure of struts may not affect much on the me-
loys (α + β type and β type), CoCr, stainless steel 316L, Ti-Ta, Ni-Ti,
chanical properties of cellular scaffolds but their entire topology due
etc., Ti-6Al-4V is considered as the optimal materials for making ortho-
to the high porosity.
paedic implants due to its excellent biocompatibility and corrosion re-
sistance, low density, and suitable mechanical properties. There are
two species of Ti-6Al-4V alloys in terms of oxygen contents, i.e. Grade 4.2. Compressive properties
5 (Owt% b 0.20%) and Grade 23 (Owt% b 0.13%), which are typically called
Ti-6Al-4V and Ti-6Al-4V ELI, respectively. They consist of two phases of It is of particular importance to have the implant's mechanical prop-
different crystal structures: α-Ti (hexagonal close-packed) and β-Ti erties similar to the natural bone at the implantation site. This will help
(body-centred cubic). In addition, hexagonal α′ martensite will occur to prevent stress shielding where excessive implant stiffness leads to
when Ti-6Al-4V is subject to rapid cooling process [11]. The addition bone resorption [77]. The compressive properties of bone depend on
of Al leads to solid solution hardening which strengthens the alloy, age and location within the body [78–80]. It has been established that
and stabilization of the α phase. By contrast, V helps to improve ductility cortical and cancellous bones have compressive strengths in the ranges

Fig. 7. Typical compressive curve for cellular scaffolds with (a) reticulated and (b) stochastic structures [62].
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1335

of 100–230 MPa and 2–12 MPa, respectively. Their Young's moduli are
in the ranges of 3–30 GPa and 0.02–0.2 GPa, respectively [81]. For
bone defects, metallic implants are preferred for their high load-
bearing abilities. However, the Young's moduli of traditionally-
manufactured metallic bio-implant are usually much higher, e.g. it is
~114 GPa for fully-dense titanium alloy implants [82].
Porous implants are primarily used in orthopaedic applications to
patch up cracks or cavities. Studies have shown that Ti-6Al-4V mesh
gave a lesser stress shielding compared to solid samples of the same di-
mensions [18]. Gibson and Ashby [83] derived the relation between the
mechanical properties of cellular solids and the relative density, ρr:

ρ
ρr ¼ ð1Þ
ρs

where ρ* and ρs are the densities of the cellular structure and the corre-
sponding solid material, respectively. Herein, the porosity is equal to
(1 − ρr). Elastic modulus of bend-dominated cellular structures, E⁎, is:

E
¼ C 1 ðρr Þ2 ð2Þ
Es

where Es denotes the bulk elastic modulus of the solid constituent

material property and C1 is a constant ~ 1 [55,84]. In general, ρr b 0.8
for cellular materials (structure consisting of connected struts). For
ρr N 0.8, the material should be considered a solid interspersed with
small holes [84]. This analysis can be extended to the failure strength
(σ*) of bend-dominated cellular solids as well:

σ 3
¼ C 2 ð ρr Þ2 ð3Þ
σ y;s

σ 3
 1

¼ C 2 ð ρr Þ2 1 þ ð ρr Þ2 ð4Þ
σ y;s
Fig. 8. Illustrations showing the 3D spatial representations of effective Young's modulus
surfaces for various representative cellular units: (a) crossing-rod unit, (b) simple cubic
where σy,s is the yield strength of the bulk solid and C2 is a constant ~0.3
unit, (c) face-centred cubic unit, (d) diamond cubic unit, (e) octet-truss unit, and (f) a
combined unit of face-centred and body-centred units (FCC–BCC) [67]. Figures adapted [55]. Eq. (4) includes a correction for cellular structures with relative
and reprinted from Ref. [67], with permissions from Elsevier. density N 0.3 [64]. Elastic modulus and failure strength of stretch-

Fig. 9. Effects of (a) pore size and (b) and (c) pore shape with regard to cell occlusion on 3D-printed metallic cellular structures [92,104]. [C] - cubic, [T] - tetragonal, and [H] - hexagonal.
1336 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343

dominated cellular structures [55] are: with cube-shaped unit cells angled at 45° to the vertical axis, were test-
ed under uniaxial compression. It was observed that while failure initi-
E 1 ated in the form of crush bands appearing at the top of each sample,
≈ ρr ð5Þ
Es 3 these bands had different directions with respect to the vertical axis
(loading direction). In the mesh samples, the crush bands were consis-
σ 1 tently at ~45° while in the foam samples, the angle ranged from 45° to
≈ ρr ð6Þ
σ y;s 3 90° [62]. It can be deduced that regular lattice structures may produce
more predictable compressive behaviour in comparison to irregular
, respectively. Nevertheless, regardless of bend- or stretch-dominated, foam structures.
metallic cellular solids would buckle before they yield when ρr ≤ 0.01 Anisotropic unit cells designs, such as the rhombic dodecahedron,
[55]. Buckling of a strut in a cellular solid mostly depends on its slender- display varying mechanical properties depending on their orientation
ness ratio (t/L), which is directly linked to the ρr. The ‘buckling strength’, to the build direction and loading axis. One reason for this is the forma-
σ∗el is: tion of columnar grains in long strut lengths parallel to the build direc-
tion, affecting the pattern of crack propagation [101]. Xu et al. provided
σ el a visual representation of the anisotropic stiffness of a variety of lattice
¼ C 3 ρr 2 ð7Þ
Es structures by plotting the Young's modulus in 3D coordinates, as
shown in Fig. 8 [67]. Hereinto, strong and weak directions were clearly
where C3 is a constant that depends on the details of the connectivity of indicated. Moreover, the dominant factor influencing mechanical prop-
the strut [55]. From the Ashby's charts in Fig. 4, it is clearly seen that a erties of lattice structures is the spatial arrangement and dimension of
linear scaling relationship between the relative mechanical properties the struts, but not the materials [93]. It must be noted that despite the
and the relative density for the ideal stretch-dominated cellular solids, CAD model, the pore shapes of actual lattice structures may be distorted
which is in good agreement with Eqs. (5) and (6). By contrast, ideal due to the fabrication process. For example, an intended hexagonal lat-
bend-dominated structures lie along a trajectory of slope 2 in the rela- tice may end up having rounded pores instead [102].
tive modulus vs the relative density log-log plot while a trajectory of
slope 1.5 in the relative strength vs relative density log-log plot, which
are consistent with Eqs. (2) and (3). The Ashby's chart is very useful
to identify if a cellular structure is bend-dominated or stretch-
dominated and to predict its mechanical properties with varying
porosities.
Due to the inherent brittleness of cellular scaffolds, their mechanical
properties are mainly evaluated by compressive means. Li et al. [19]
conducted compressive testing on 5 cellular Ti-6Al-4V samples fabricat-
ed using SEBM. These samples possessed a fully interconnected honey-
comb pore structure with pore size of 1108 ± 48 μm, strut diameter
750 ± 36 μm, and distance between struts in the z-direction 1.386 ±
0.163 mm. Overall porosity was calculated to be 66.3 ± 2.1%. Their
work mirrored the behaviour of cellular metallic materials subjected
to compression, as observed by bending or elastic compression of cell
walls in the linear elastic deformation stage, before buckling and plastic
yielding of cell walls. It was found that these ~ 66% porous Ti-6Al-4V
samples had a maximum compressive strength of 116 MPa and elastic
modulus of 2.5 GPa which are comparable to the properties of human
cancellous bone [19]. Mechanical properties of cellular Ti-6Al-4V scaf-
folds are highly dependent on their porosity. Fig. 5 clearly shows that
both of Young's modulus and strength decrease with the increase in po-
rosity. Based upon the datum given in Fig. 5, Ashby charts (namely plots
of relative modulus or relative strength vs relative density on logarith-
mic scales) were plotted as shown in Fig. 6. It can be seen that most of
the designed Ti-6Al-4V cellular scaffolds are bend-dominated currently.
Stretch-dominated cellular design is still needed because it enables low
modulus but high strength at high porosities.
It is worth noting the way that a cellular structure deforms when
crushed. As observed by Cheng et al. [62], meshes and foams with differ-
ent porosities displayed similar stress-strain curves but different me-
chanical behaviour. The stress-strain curves plotted to gather the
results across all samples showed that these cellular structures had a
stage of elastic deformation till a peak stress value, followed by a drop
to a plateau region where fluctuations in stress occurred and lastly, a
stage of rapid increase in stress caused by densification as the material
crushes together, as illustrated in Fig. 7 [62]. It was thus concluded
that the 3D-printed metallic cellular structure, whether stochastic or re-
ticulated, was brittle. This was specifically indicated by the fluctuations
in the plateau region [100], as compared to ductile materials having a
Fig. 10. (a) Microradiography, (b) micro-CT and (c) back-scattered SEM with element
smooth plateau region. However, there are clear differences on defor- maps after in vivo implantation illustrating bone ingrowth [20,21,114]. Figures adapted
mation behaviour for stochastic and reticulated structures. Samples of and reprinted from Ref. [20] and [114], with permissions from John Wiley & Sons and
open cellular Ti-6Al-4V, for foam structures and for mesh structures Elsevier.
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1337

Van Bael et al. [92] conducted an experiment to investigate how dif- properties, i.e. increasing the amount of material increases mechanical
ferent pore shapes and sizes in lattice structures would affect their me- properties while decreasing permeability for a particular cellular
chanical properties. Six different unit cell configurations were tested, scaffold design. In addition, different cellular designs will lead to
consisting of three shapes (triangular, hexagonal, and square) of two different mechanical properties and permeability for a given porosity
sorts of pore sizes each (500 and 1000 μm) in the horizontal plane. [12].
Pore sizes were derived from the diameter of a circle inscribed within
the pore shapes, similar to Arabnejad et al.'s method [25]. Both horizon- 5. In vitro and in vivo tests for orthopaedic implantation
tal and vertical strut thickness were kept constant at ~200 μm across all
unit cell designs [92]. Compressive testing was carried out on the lattice Bone consists of an outer dense shell (i.e. cortical bone) covering a
samples and it was found that the lattices with hexagonal pores had the porous, spongey centre (i.e. cancellous or trabecular bone) [43,44].
highest compressive strength. However, when designing scaffolds for Bone ingrowth occurs in cellular implants when cells enter and migrate
orthopaedic implants, it is important to consider the compressive prop- through the pores and attach onto surfaces in inner regions. Thereinto,
erties of natural bone. Triangular and square porous designs (for both propagation will start as cells grow and multiply, eventually forming
pore sizes) had mechanical properties close to that of cancellous bone, new bone anchored to the implant. Ponader et al.'s experiments con-
with compressive stiffness ranging from 454 ± 40 MPa to 2840 ± firmed that a solid titanium implant would not stimulate bone growth
155 MPa. As for cortical bone, it was found that the design with smaller and regeneration, reinforcing the need for a porous structure [20]. As
hexagonal pores was more desirable [92]. As mentioned in previous sec- mentioned in previous sections, implants with the optimal cellular de-
tions, designing the ideal cellular implant involves balancing mechani- signs requires mechanical suitability together with sufficient permeabil-
cal suitability with permeability within the bound set by material ity. Designed cellular structures should have maximized permeability

Table 3
Histology images after in vivo implantation of titanium scaffolds, indicating bone ingrowth. Figures adapted and reprinted from Ref. [20,102,112,114,115], and [117], with permissions
from Elsevier and John Wiley & Sons .

Animal Implantation Time

model site span Histology Description

Rabbit Tibia [102] 2 wks Pore size of implant increases from left to right. After 8 weeks, new bone remodeled into
4 wks mature lamellar bone in all samples. Marrow-like tissue was evident inside the porous
8 wks implants.
Silver: Implant
I: Bone ingrowth
*: Marrow-like tissue spread into porous area

Femur 6 wks After 6 weeks, bone tissue follows the surface irregularities of implants. After 12 weeks, newly
[112,114] 12 wks formed bone with visible cell nuclei was observed.
Red: Newly formed bone tissue

Calvaria [116] 4, 8 & Rapid increase of bone ingrowth.

12 wks

Sheep Femur [21,117] 26 wks Bone-implant contact was observed throughout the entire porous scaffold

Anterior ~13 wks After 3 months, thin layer of fibrous tissue- or cartilage-implant bonding were observed in
cervical fusion ~26 wks some bone-material interface regions. After 6 months, mature bone tissue bonded closely with
[115] struts of implant.

Pig Calvaria [20] 2, 4 & Bone-implant contact and bone ingrowth increased with time. After 60 days, bone structure in
8 wks the most outer region of the implants was similar to pristine bone.
1338 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343

for cell migration and mass transport, but whose effective linear elastic While the minimum pore size that could support bone ingrowth was
properties match those of natural bone tissue [12]. For satisfactory bone found to be ~50 μm, suggested pore sizes exceed 300 μm [107]. In cases
ingrowth to happen, many characteristics such as porosity, pore shape of very small pore sizes, it is possible for single cells to stretch and
and size, and material have to be optimised. Previous studies have bridge across the pore diameter. Accordingly, there was high chance
found that interconnected porosity of no less than 40% (the lower of cell occlusion “clogging up” the scaffold surface in initial periods.
limit of cell penetration and migration) [103] and pore size of This causes a lack of ingrowth of cells into the pores which is undesir-
50–800 μm [18,25] are generally sufficient for satisfactory bone in- able [105]. These results are agreeable with Van Bael et al.'s studies,
growth. These results were obtained by evaluating the cellular implants where it was found that larger pores provided more open space for
in in vitro or in vivo environments. cell growth and proliferation [92]. Moreover, in metal 3D printing,
small pore sizes have high difficulty in fabricating satisfactory samples
5.1. In vitro studies: cell attachment, proliferation and occlusion of fine definition [104].
Bone cells are anchorage-dependent [110] and it was found that cell
Biocompatibility of the 3D-printed cellular structures can be studied growth was skewed towards corners [92]. Accordingly, higher cell
by an in vitro bone (osteo-) cell culture on the samples. The initial cell growth was observed in the designs with the more corners [111].
attachment on the scaffold surface is commonly studied by scanning Fig. 9b and c reveals the influence of pore shape on cell occlusion in
electron microscopy (SEM). If the scaffold surface is biocompatible, ad- 3D-printed tetragonal and hexagonal cellular structures. However, the
hesion of cell pseudopodia on the surface for cell movement and scaf- difference was small in the smaller pore sizes regardless of pore
fold invasion will be observed under SEM [104,105]. Cell proliferation shape. These results concurred with that of Rumpler et al. in that smaller
in the scaffolds can be quantified by the measurements of the cellular pore sizes (~ 500 μm) encouraged cell growth better than larger ones
DNA synthesis, metabolic activity [92,105], ATP concentration or prolif- [111]. At the same time, large pore sizes (~ 1000 μm) allowed better
eration markers (antigens) over time. Meanwhile, the cell viability on flow of cells into the inner lattice region leading Van Bael et al. to sug-
scaffolds is usually evaluated using live/dead staining [92]. The alkaline gest a graded lattice structure [92].
phosphatase (ALP) levels are evaluated as an early marker of osteoblast
differentiation [92,105]; the osteoblastic mineralization is determined 5.2. In vivo studies: bone regeneration and ingrowth
by using Alizarin red-S staining [106].
Factors such as pore size [107] or pore throat size [108] play an im- Another aspect for consideration regarding the performance of tita-
portant role in the effectiveness (rate) of bone ingrowth. Effect of pore nium implants is the level of in vivo bone regeneration and ingrowth
size on effectiveness and speed of bone ingrowth into cellular struc- into the porous implant. Fig. 10 presents the three methods that were
tured implants can be studied indirectly by using in vitro cell culture. commonly used to characterize bone tissue ingrowth after in vivo im-
In terms of Zhang et al.’s work, pore size and interconnectivity are plantation. Early researches have shown the ability of bone growth fol-
key factors in optimising the flow of nutrients and waste, leading to lowing the irregularities of the implant surface in femur and tibia of
better osseointegration [59,109]. In a study conducted by Warnke rabbits [112]. Ponader et al. conducted an in vivo study using Ti-6Al-
et al., Ti-6Al-4V meshes of pore size ranging from 450 to 1200 μm 4V lattices with a mean pore size of ~ 450 μm and implanted into the
were tested for rates of occlusion by osteoblasts, signifying bone in- skulls of pigs [113]. Original bone surrounding the implants was mea-
growth. It was found that there was thorough occlusion for the sured for control in quantifying the amount of new bone grown. The im-
450 μm sample, and a decreasing proportion of occluded pores through plant was divided into three regions (i.e. outermost, middle, and inner)
the rest of the samples with increasing pore sizes. No occlusion was ob- to distinguish areas of new bone development. Microradiographs were
served in the samples with large pore sizes (900–1200 μm) [104]. Fig. 9a used to observe that there was only minimal bone development in the
shows the influence of pore size on cell occlusion for the 3D-printed outermost region of the implant after 14 days. After 30 days, there
cubic lattice structures. was observable bone ingrowth in the inner and outermost regions.

Fig. 11. (a) Illustration of influence of pore size on cellular scaffolds. Schematics showing (b) variation of specific surface area for cell growth and vascularization of cellular scaffolds with
pore size; and (c) variation of mechanical strength and permeability of cellular scaffolds with pore size and porosity.
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1339

Fig. 12. CAD models (a) incorporating inner foam element and outer S3 bone element, (b) different density inner and outer foam elements, and (c) inner foam and outer mesh elements for
a femoral rod prototype (half-section view). (d) SEBM-fabricated femoral rod prototype with a cellular structure similar to (b) [63, 72].

Fig. 13. Flow chat illustrating the design-manufacturing-testing-implantation process of cellular scaffolds for orthopaedic implants produced by metal 3D printing technologies.
1340 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343

The implant was thoroughly filled with bone after the 60 days' mark. rough surfaces (between 1 and 2 μm) are best to promote bone cell
Quantification of these results was performed by calculating the per- growth [122]. Xue et al. conducted in vitro tests comparing cell growth
centage of bone volume with respect to the porosity of the implants, on 3D-printed porous titanium structures and smooth, solid titanium
taking into account the extent of penetration of bone growth into the form. It was observed that cells had good adhesion onto the rough sur-
implant. The density of the new bone however, fell short of that of the face of porous structures. This was demonstrated by the spread-out
surrounding original bone. shape of the cells providing great surface contact with the porous struc-
Table 3 compiles some recent works reporting bone tissue ingrowth ture. Moreover, the cells demonstrated the ability to conform and attach
after in vivo implantation of titanium scaffolds into different animals. to the irregular surface [105].
Previous results have shown successful bone ingrowth into cellular scaf- Murr et al. [72] envisioned the next generation of biomedical im-
folds comparing to the solid counterparts [20,21,102]. Wu et al. [115] plants with complex functional cellular structures fabricated by using
compared the in vivo performance of a conventional poly-ether-ether- metal additive manufacturing technologies. Some examples of these
ketone (PEEK) interbody fusion cage with a SEBM-printed Ti-6Al-4V kinds of complex functionally graded cellular scaffolds are shown in
cellular scaffold in sheep. The porous Ti-6Al-4V cage has a fully inter- Fig. 12. Van Bael et al. [92] suggested the use of graded lattice designs.
connected porous structure with porosity of ~ 68% and pore size of Instead of having a single pore size throughout the implant, a function-
~ 710 μm. It was illustrated that Ti-6Al-4V cages, when comparing ally graded structure consists of large pore sizes in the outer region and
with the PEEK cages, promoted better osteointegration with higher smaller pore sizes in the inner region. This helps to encourage transpor-
degree of bone-material binding and achieved a higher efficiency in tation of nutrients and oxygen deeper into the implant where cells
bone ingrowth. Taniguchi et al. conducted a recent study to investigate attach and grow. Larger outer pores also prevent occlusion on the im-
the optimal pore size of SLM-fabricated pure titanium implants in an plant surface, encouraging bone ingrowth [92]. 3D printing is beneficial
in vivo environment. Three pore sizes were studied (300, 600, and in these cases because of its flexibility to manufacture different pore
900 μm) at 2 to 8 week marks, and an interesting finding was made sizes within the same build [123,124]. Hence, it is possible to rigorously
with regards to bone-implant fixation. Beyond the 4 week mark, the im- design and manufacture graded cellular structures that optimise both
plants across all pore sizes displayed very high bone-implant fixation the requirements of mechanical reliability and satisfactory bone in-
[102]. growth [25]. In practical, however, powder removal from inner fine cel-
Past studies have had varying results with respect to the relationship lular regions will become extremely difficult for big-sized printed parts
between pore size and bone ingrowth. Initially, Itala et al. proposed that using SLM or SEBM. It has been concluded that it is important to strike
the range of pore sizes optimising bone ingrowth was 100–400 μm. a balance between suitable mechanical properties and decent
They additionally claimed that (disregarding manufacturing limita- manoeuvrability for cell ingrowth, in the design of cellular orthopaedic
tions) there was no lower limit for pore sizes for effective ingrowth implants [81]. Meanwhile, many manufacturing limits (e.g. minimum
[118]. This was agreed to by Braem et al. who applied a microporous ti- strut thickness, minimum pore size, tapped powder removal, etc.) and
tanium coating to rabbit tibia, and discovered formation of new bone availability of powder materials have to be taken into account. Based
within pores smaller than 10 μm [119]. However, the rate of bone in- on the review above, Fig. 13 illustrates a general flow chart from design
growth was found by Taniguchi et al. to increase with pore size. 3D- to implantation for cellular scaffolds manufactured by metal 3D printing
printed porous titanium scaffolds were likewise implanted into rabbit methods, where only some of key factors are listed. It should be noted
tibia and bone ingrowth in 600 μm and 900 μm pores exceeded that in that cellular scaffolds with more cell-favourable hierarchical designs
the 300 μm pores [102]. This was explained by vascularization that is and more matchable performance to the specific human body are still
important for bone tissue formation. Large pores are believed to favour needed in the long run.
vascularization and there is no marked increase in extent of vasculariza-
tion with a pore size above ~400 μm [120]. In addition to vasculariza- 6. Concluding remarks
tion, factors such as specific surface area of scaffolds, are essential
factors with respect to fixation ability. Scaffolds with smaller pores are It is concluded that the requirements for a prosthetic orthopaedic
considered to have larger surface area and therefore more space for implant are to (i) fill the 3D defect cavities, (ii) be biocompatible,
bone tissue ingrowth [81]. Based on the previous reports stated (iii) have attractive surface morphology for cell attachment and
above, we summarize the comprehensive influence of pore size proliferation, (iv) be sufficiently strong but have stiffness close to the
on cellular metallic bone implantation as shown in Fig. 11. It is thus surrounding bone tissues, and (v) have adequate porosity with 3D
suggested that an optimal pore size is supposed to be ~ 300–600 μm interconnected pores. However, increasing the density of structure
in order to possess excellent performance via a trade-off (decreasing the porosity) enhances mechanical properties while
between bone ingrowth, vascularization, mechanical strength and decreasing permeability for a particular cellular scaffold. The ideal is to
permeability. create strong load-bearing structures using as little material as possible,
or where this is useful to be as light and as elastic as possible. Stretch-
5.3. Scaffold designs favouring cell ingrowth dominated cellular scaffolds are found to be structurally stronger than
the bend-dominated ones and they can be remarkably strong despite
It has been reported that surface of implants affects the implant's their very low density. While their feasible design space for manufactur-
bone regeneration. Implant surfaces can be naturally occurring (de- ing by powder-bed based 3D printing techniques is relatively narrowed.
pending on the fabrication process and parameters [121]), or can be In order to fulfil all the orthopaedic implant requirements, especially
treated to achieve specific surface topographies. In Wild et al.’s study, cater to the contradicting porosity and mechanical properties, a newly
three types of implant surface were examined: untreated 3D-printed proposed specification for the orthopaedic implants is the functionally
(by SLM), sandblasted, and sandblasted with acid etching. It was ob- graded cellular structure from highly porous with large pores at the
served using SEM that the untreated surface was covered by spherical outer region of the prostheses to a denser structure at the core region.
sintered powder. The pore size in the untreated samples was hence Metallic 3D printing has extremely high potential in the biomedical
significantly smaller than designed. The untreated sample also lacked field. Its ability to produce intricate designs that mimic the properties of
the roughness of the treated samples, which exhibited flaky and naturally-occurring structures (in bone, etc.) is unmatched by other tra-
“pockmarked” surfaces. Further experiments proved that the ditional manufacturing methods. However, no manufacturing method
sandblasted surfaces with or without acid etching were able to signifi- is perfect, and 3D printing remains costly and prone to process compli-
cantly increase the amount of defects bridging by bone [22]. These re- cations. A certain amount of calculated prediction is still required [125],
sults were congruous with earlier studies proclaiming that moderately but this is still the cause of mechanical and microstructure defects in the
 X.P. Tan et al. / Materials Science and Engineering C 76 (2017) 1328–1343 1341

builds [126,127]. Another key disadvantage of 3D printing is that it can- [20] S. Ponader, C. Von Wilmowsky, M. Widenmayer, R. Lutz, P. Heinl, C. Körner, et al., In
vivo performance of selective electron beam-melted Ti-6Al-4V structures, J. Biomed.
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ly covered by many researchers, with many varying results. This is Bone regeneration by the osteoconductivity of porous titanium implants
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