Medical & Biological Engineering & Computing (2021) 59:1673–1689

https://doi.org/10.1007/s11517-021-02361-7

REVIEW ARTICLE

The advances of topology optimization techniques in orthopedic

implants: A review
Naichao Wu 1 & Shan Li 2 & Boyan Zhang 1 & Chenyu Wang 1 & Bingpeng Chen 1 & Qing Han 1 & Jincheng Wang 1

Received: 29 February 2020 / Accepted: 5 April 2021 / Published online: 7 August 2021
# International Federation for Medical and Biological Engineering 2021

Abstract
Metal implants are widely used in the treatment of orthopedic diseases. However, owing to the mismatched elastic modulus of the
bone and implants, stress shielding often occurs clinically which can result in failure of the implant or fractures around the
implant. Topology optimization (TO) is a technique that can provide more efficient material distribution according to the
objective function under the special load and boundary conditions. Several researchers have paid close attention to TO for
optimal design of orthopedic implants. Thanks to the development of additive manufacturing (AM), the complex structure of
the TO design can be fabricated. This article mainly focuses on the current stage of TO technique with respect to the global layout
and hierarchical structure in orthopedic implants. In each aspect, diverse implants in different orthopedic fields related to TO
design are discussed. The characteristics of implants, methods of TO, validation methods of the newly designed implants, and
limitations of current research have been summarized. The review concludes with future challenges and directions for research.

Keywords Topology optimization . Finite element analysis . Orthopedic implants . Global layout structure . Hierarchical structure

1 Introduction
Metals and their alloys have commonly been used as bone
implants for several orthopedic diseases for a long time.
Sometimes, the implant serves as the bone substitute in vari-
ous types of replacement surgery. In some other cases, it could
provide a strong mechanical support for damaged bone.
However, studies have reported some complications that
may occur simultaneously because of the mismatched me-
chanical properties between the bone and implant [1, 2]. For
example, the elastic modulus of Ti-6Al-4V is around 110
GPa, while that of cortical bone ranges from 3 to 30 GPa
and of trabecular bone, between 0.02 and 2 GPa [3].
Obviously, the implants are stiffer than the adjacent bone,
which can lead to stress shielding. Additionally, osteoporosis
* Qing Han
my.hanqing@163.com
* Jincheng Wang
jinchengwang@hotmail.com
1
Department of Orthopedics, Second Hospital of Jilin University,
Changchun 130041, China
2
Dermatological Department, Second Hospital of Jilin University,
Changchun 130041, China
may occur in the area without enough stress on account of the
stress shielding. Moreover, prosthesis loosening and patho-
logical fracture may also occur [4, 5]. Eventually, revision
surgery is required, which considerably affects the quality of
life of patients. Efforts to narrow the gap in elastic modulus
between the bone and implant have shown improved results in
lowering stress shielding [6, 7]. Therefore, the design methods
of orthopedic implants continue to capture researchers’ atten-
tion to determine the perfect implant structure to achieve better
biological and biomechanical function.
Studies in orthopedics have focused on the global layout
and local structure of the implant to seek more rational bio-
mechanics and achieve better-matched implants. There are
three methods of structure optimization: size optimization,
shape optimization, and topology optimization (TO).
Initially, TO was applied to mechanical designing in the avi-
ation and spaceflight industry to help determine the distribu-
tion of material on the global layout structure [8, 9]. Ever since
the 1980s, TO has been regarded as a powerful tool for im-
plant design [10]. The fabrication of TO-designed structures,
especially the detailed parts, were complex and challenging
for conventional manufacturing techniques. Nowadays, addi-
tive manufacturing (AM) techniques can overcome this limi-
tation. An increasing number of researchers have designed
orthopedic implants by using the TO technique to attain new
1674
implants with better biomechanics. Wang et al. provided a
summary of TO techniques about metallic porous structures
[11]. Most of the recently published literature has focused on
the topological design of porous or cellular structures. In this
review, we discuss the TO design concerning the material
distribution of the global layout or hierarchical structure to
understand the current advances of TO in bone implants.
Following a brief introduction of the TO and AM techniques,
the advances of TO in orthopedics will be reviewed in detail.
2 TO and AM techniques
Originally, TO techniques were widely applied in the aero-
space and automobile industries. In the past few decades, TO
has become popular among researchers interested in designing
medical implants to achieve better biomechanical properties
on account of its function of adjusting the material distribu-
tion. TO has been regarded as a powerful tool for implant
design at the base of finite element analysis (FEA). Since
1972, FEA has undergone rapid development to mimic the
working situation of the complex bone-implant junction
[12]. The FEA method is a powerful simulation tool used to
analyze and redesign the implant structure, as the structure can
be changed easily before actual manufacture in computer-
aided designing (CAD) software. At the base of FEA, TO
provides a novel method to optimize mechanical function by
redesigning the distribution of material in a designated do-
main. This distribution depends on the specialized loading
and boundary condition constraints that are subject to the ob-
jective function to minimize or maximize certain properties of
the structure [13]. In orthopedics, the objective function of
most research is to get implants with minimum compliance
(minimum strain energy). According to Li et al., the design
domain is discretized into finite elements, after which the TO
technique will identify whether this designated element has
enough levels of stress; otherwise, the designated element
would be removed to increase the overall efficiency [14].
Thus, a scaffold with holes or a truss-like structure can ulti-
mately be obtained by TO. Hollister et al. described TO as
“the art of scaffolding is where to put the holes and the bio-
factors”; TO would serve as an efficient tool to determine the
location, shape, and size of the holes [15]. At present, FEA
software such as Abaqus (Dassault Systemes, Providence,
RI), Ansys (Swanson Analysis System Inc., Houston, TX),
and Hypermesh (Altair Engineering, Troy, MI) can complete
the iterated TO operation by using a specialized algorithm.
From the theoretical perspective, the methodology of TO al-
gorithm is based on the variable density methods (solid iso-
tropic material penalization (SIMP) model), homogenization
method, moving morphable component (MMC) method,
moving asymptotes (MMA) method, evolution structural op-
timization (ESO) method, and level-set method [16–21].
Med Biol Eng Comput (2021) 59:1673–1689
In general, the redesigned structure is so complex
that conventional manufacturing methods cannot repro-
duce it. However, AM makes it possible to fabricate the
TO-designed structures. Thus, AM techniques have be-
come the preferred tool to fabricate various medical im-
plants such as customized prostheses and implants with
hierarchical irregular structures. In the past decade,
powder bed fusion (PBF)–based AM methods emerged
and the techniques are becoming increasingly mature
recently such as selective laser sintering (SLS), direct
metal laser sintering (DMLS), selective laser melting
(SLM), laser engineered net shaping (LENS), and elec-
tron beam selective melting (EBSM). SLM and EBSM
were commonly applied in fabricating orthopedic im-
plants, especially the cellular porous structure in local
structure [22]. With the development of the AM tech-
niques, the constraints of printing precision, the struc-
tural anisotropy, and the pore connectivity of the porous
structure have been gradually conquered. Much more
similar mechanical and biological properties of the scaf-
folds with those of trabecular bone could be fabricated
[23–27]. Clinically, AM techniques have been widely
used in orthopedics. For instance, preoperative design-
ing and personalized intraoperative navigation can be
carried out to ensure more accuracy in surgery with
the help of a 3D-printing model. Customized implants
fabricated by AM will reduce intraoperative blood loss,
operative time, and the rate of postoperative complica-
tions [28, 29].
3 Advances of TO techniques in orthopedic
implants
Advances in the TO technique for orthopedic implants are an
interdisciplinary science of bone tissue engineering and me-
chanical engineering. Recently, many studies have addressed
how to overcome the current limitations of metallic implants.
Al-Tamimi et al. summarized the major research activities in
bone fixation implant with the novel TO method as Fig.
1 [3]. In this article, we further reviewed the available
correlational research in detail using TO in different
fields of orthopedics that focused on two different de-
sign domains—the global layout structure and hierarchi-
cal structure in recent years. The global layout structure
is designed mainly for appropriate biomechanics and the
hierarchical structure also takes into consideration the
biological property benefits [30–32]. Figure 2 presents
the research in related fields of orthopedics. In this ar-
ticle, the detailed research aspect of both domains, the
material, methods of TO, characteristics, and limitations
of the TO-designed structure are discussed.
Med Biol Eng Comput (2021) 59:1673–1689 1675

Fig. 1 The related research

activities in bone fixation implant
with the novel TO method
summarized by Al-Tamimi et al.
To avoid the need for a second
surgery to remove the implant by
replacing metallic materials with
biocompatible and degradable
materials. To reduce the stress
shielding phenomena by reducing
the equivalent stiffness of the
metallic implants through the use
of TO. To ensure the rationality
and safety of the prosthesis bio-
mechanics, mechanical simula-
tion, additive manufacturing, and
validation experiments in vivo/in
vitro were operated by researchers
[3]

Fig. 2 Advances of TO
techniques in orthopedic
implants. The related research
using TO in different fields of
orthopedics (trauma surgery,
maxillofacial surgery,
arthroplasty, and spine surgery)
focused on two different design
domains—the global layout
structure and hierarchical struc-
ture. There are two stages of hi-
erarchical TO: TO design of
global layout structure and TO of
local microstructure. The local
microstructure refers to different
porous structures
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3.1 TO design of the global layout structure in
orthopedic implants
The global layout structure of the implant should be consistent
with the homologous anatomical structure. Metallic materials
with different material distribution but having the same mass
or volume would lead to different biomechanical perfor-
mances. Most studies had two main aims concerning the glob-
al layout structure of the TO design. The first aim was to
reduce the weight or reduce the stress shielding caused by
the mismatching mechanical properties of the bone and the
implant. Previous studies showed that the TO technique could
result in more lightweight implants with reduced “equivalent
stiffness” [33–35]. The second aim was to determine whether
the redesigned implants with holes could provide space for
bone ingrowth or bone grafting [36]. An increasing number
of studies are researching to establish novel methods to get
better implants by the TO technique.
As for the global layout structure designed with TO, studies
mainly focused on the material distribution at the level of the
macrostructure of implants rather than the microstructure.
Research has mainly focused on the following topics:
3.1.1 TO design of the global layout structure of the implant
in trauma surgery and maxillofacial surgery
Bone fractures or defects often occur in trauma surgery and
maxillofacial surgery. Internal fixation plates or relevant pros-
theses are usually implanted into the body for bony recovery
of the damaged bone. A majority of trauma patients need to
undergo open reduction with internal fixation (ORIF) to fix
bone fractures. Internal fixation implants such as plates and
screws are used to ensure the stability of fixation for broken
ends of the fractured bone. Stress shielding caused by the
“stiffer” plate would lead to osteoporosis in the area without
enough stress. Delayed union and nonunion of bone might
also occur on account of stress shielding [37–39]. Most of
the studies focused on the design of plates, such as the shape,
thickness, location, and number of screws to satisfy the bio-
mechanical criterion. In this process, TO can act as a powerful
tool. Unlike the traditional implants, the TO-designed im-
plants focus on optimal material distribution to generate a
stiffness match between the implant and bone tissue by min-
imizing the strain energy. It is worth mentioning that Al-
Tamimi et al. have attempted to make a TO-designed plate
for ORIF. They optimized the titanium alloy (Ti6Al4V) fixa-
tion plate without assembling the plate with the bone [3, 30,
33, 40]. They used the SIMP model, which was one of the
most efficient and commonly used material interpolation
models among the variable density methods [41, 42].
Different values of volume reduction under different loading
conditions (i.e., bending, torsion, and tensile) for the fixation
plate were considered with the help of the Abaqus software.
Med Biol Eng Comput (2021) 59:1673–1689
The volume and equivalent stiffness of the new plate was
reduced. They verified its feasibility to obtain a plate that
can minimize the stress shielding phenomenon by TO method.
It was a tentative exploration to design the plate based on TO
without considering the contact between bone and plate. Then,
they evaluated the changes in bone stress and stress shielding
of their newly designed plate [43]. The results of less stiff
plates with adequate mechanical strength and more stress
transferred to the bone fracture plane made them ensure the
availability of TO in decreasing the stress shielding. The re-
search was terminated at the FEA stage. Not only these, they
conducted further research in which mechanical and biologi-
cal verification was considered [30]. The necessity to post-
process the produced plates was also discussed in their study.
Subsequent researchers began to optimize the plate during
assembly for a particular bone fracture. To simplify the mate-
rial property of the bone, it was assumed to be a homogenous
material in most studies. Lovald et al. used TO and the Ansys
software to design a bone plate for mandibular body fracture,
which could provide maximum fracture stability with minimal
implanted volume and patient intrusion [44]. The newly de-
signed plate was based on the original shape of the conven-
tional one. Teo et al. also optimized a mandible fracture plate
based on TO to reduce the volume of the miniplate [45]. Using
the Abaqus software, Liu et al. reconstructed a CT-based 3D
virtual mandible with a fracture, and an FEA model was cre-
ated to analyze the stress condition under three loading con-
ditions and constraints [46]. Distinct from most other research,
the mandible was regarded as inhomogeneous material. In this
case, the FEA results were more likely to be accurate because
the material property would be more similar to natural bone.
The property of bone was calculated as Hounsfield Unit (HU)
value based on CT images. Finally, a V-patterned new plate
was created innovatively with the TO method. The newly
designed plates showed better biomechanical performance.
With the advancement of AM techniques, it may potentially
be possible to make more specialized plates for different man-
dibular body fractures. Ouyang et al. explored the fixation
plate of calcaneal fractures, but not bone fractures of the max-
illofacial region [47]. Using the same routine as in Al-
Tamimi’s studies [3], the TO technique was used with the help
of Abaqus software to create a minimized profile without loss
of fixation stability. It is well-known that mandibular
distractor plates are used in mandibular distraction osteogen-
esis to correct mandibular retrognathia. Sensoy et al.
redesigned the mandibular distractor plates with TO and par-
ticle swarm optimization (PSO) [48]. PSO is one of the
metaheuristic optimization techniques in the field of biome-
chanics [49]. A new plate with less displacement and compli-
ance was obtained. The screw positions of the plate appeared
more suitable for biomechanics. All the above studies
redesigned plates without considering bone remodeling in
the healing stage. Wu et al. suggested a bone remodeling
Med Biol Eng Comput (2021) 59:1673–1689
algorithm combined with TO algorithm to obtain a time-
dependent TO design through a jaw reconstruction problem
[50]. Their study was the first when time-dependent sensitiv-
ity analysis was taken into consideration in the TO design
process. This method might be extended to studies about the
TO design of bone implants in other fields of orthopedic
medicine.
Besides, the bone defect can occur in cases of bone tumor
resection or severe trauma. As for the treatment of the bone
defect, the defect could be reconstructed using two methods:
one is by using a plate to provide stability between the remain-
ing bone stumps, and the other is by implanting a prosthesis to
reconstruct the integrality of bone. Lemon et al. created a
newly designed reconstruction plate used to bridge large man-
dibular defects by the TO technique [51]. The Hypermesh and
SimLab software were used in their studies. Also, some sug-
gestions about the location and number of screws were pro-
vided. The TO process could automatically determine whether
it was necessary to put in one screw in a designated location.
The research was discontinued at the FEA model without
further verification tests.
Patient-specific implants are another method to treat bone
defects, as these can be inserted as a bone substitute into the
corresponding defect location to complete bone reconstruc-
tion. In such a situation, the TO technique can be helpful in
implant design. Sutradhar et al. worked on this kind of opti-
mization study about implants [52]. Customized implants
were obtained by the Boolean operation. Then, the implants
were redesigned by TO and fabricated by 3D printing.
Mechanical tests were operated to validate these newly de-
signed implants. They assembled the topology optimized im-
plants with a CAD skull model together instead of inserting
the implants into a cadaver or patient. Another innovation
point was that the Digital Image Correlation (DIC) method
was used during the test [53]. The DIC method could provide
a full-field strain measurement and continuous deformation
field data. This combination of novel design and mechanical
testing approach to obtain patient-specific implants proved
feasible for mid-face craniofacial reconstruction. Dai et al.
also optimized the maxillofacial prosthesis based on TO.
Both these studies discussed different cases of maxillectomy
[54]. However, Dai et al.’s study only discussed the FEA
models. Further biomechanical experiments should be con-
ducted to validate the behavior of newly designed implants.
Most of the other studies were consistent with Sutradhar
et al.’s methodology in terms of design and validation of the
newly designed patient-specific implants [46, 55]. Carlos et al.
reviewed the methodology for the design, optimization, and
fabrication of customized craniofacial implants [56]. Except
for the bone defect after cranial tumor resection, those defects
after tumor resection at the pelvis often require a customized
implant for the anatomical structure and functional reconstruc-
tion of the pelvis. Iqbal et al. designed a customized pelvis
1677
implant for the first time by using the TO technique and SIMP
model. Accordingly, one low weight and sufficiently strong
implant with the shape closely matching the pelvic bone de-
fect was obtained [57]. Then, the TO-designed implant was
fabricated by the EBSM technique in Ti6Al4V. Finally, the
TO-designed implant was successfully implanted in one pa-
tient with a pelvic bone tumor. The short-term follow-up was
satisfactory. This was the first step that the TO-designed im-
plant was implanted into the body.
3.1.2 TO design of the global layout structure of hip or knee
joint prosthesis in arthroplasty
A significant number of total joint arthroplasty operations are
performed annually worldwide [58]. Of these, total hip
arthroplasty (THA) is the most commonly performed surgery.
The designs of hip prostheses are always vital in THA.
Subsidence of femoral prosthesis, aseptic loosening of the
prosthesis, and fractures around the prosthesis on account of
stress shielding were the three main challenges faced by sur-
geons [59–61]. It is worth mentioning that a large number of
studies were interested in the TO design of the hip stem to
decrease stress shielding between the femur and hip stem. The
studies were developed from macrostructure to microstructure
in terms of the design domain. The bone material was devel-
oped from homogeneous to heterogeneous. Notably, the con-
tact condition was taken into consideration. In other words,
the linear analysis of FEA was transformed into the nonlinear
analysis, which means that the analysis programs were more
complicated, and the simulations were more realistic to the
working condition of the hip stem. TO acted as a powerful
tool in designing the 3D finite element femur model in
Fernandes and Bagge’s studies [62, 63]; however, the authors
did not assemble the femur model with prosthetic devices.
Munteanu et al. also optimized the femoral stem with a 15%
mass reduction; the newly designed prosthesis also could meet
the ISO 7206/4 and ISO 7206/6 standards (implants for sur-
gery, partial and total hip joint prostheses) [64]. Fraldi et al.
designed the global layout structure of a hip prosthesis using
TO method [65]. This study is important in that it used a
different material property reconstruction process for the
bone, and the consideration of friction between hip stem and
femur was taken into consideration. Based on these studies,
Kharmanda proposed an integrated form of multi-objective
structural optimization to improve the performance of the
Austin–Moore model [66]. In their study, TO was regarded
as an efficient conceptual design stage followed by shape
optimization. The shape optimization aimed to address the
requirements of the detailed design. They could prove that
TO promoted both reliability and durability performance.
The results could also be used to predict the direction of the
new stages of multi-objective structural optimization integra-
tion. Niroomand et al. presented the complete process of
1678
optimizing and verifying the redesigned implant in the aspect
of FEA, using the Abaqus software with the help of the SIMP
method [67]. Von Mises stress distribution and displacement
values of the two implants were compared to demonstrate the
advantages of the TO-designed implant. Except for the SIMP
method, researchers never stop researching various optimiza-
tion methods to optimize the hip stem prosthesis. Abass et al.
compared different optimization methods including confor-
mal lattice structures, level set method (LSM), shape optimi-
zation method, and SIMP to conclude the effectiveness of
various methods [68]. The results showed a similar effect of
SIMP and LSM in reducing stress shielding, while the confor-
mal lattice structures led to an increase in stress shielding
because of its localized high contact structures. Another clas-
sical application of TO in the variable density method, other
than SIMP, was evolutionary structural optimization (ESO)
[69]. Rahchamani and Soheilifard optimized the cementless
Tri-Lock prosthesis (DePuy Synthes) through the bi-
directional evolutionary structural optimization (BESO) meth-
od, based on ESO [70]. The BESO method not only allows the
material to be removed from the implant but also allows the
material added to a structure. This study validated that the
stress concentration of the optimized implant was reduced,
as was the stress shielding of adjacent bone.
Furthermore, apart from designing implants, TO was also
found to be a useful tool for femur and femur/implant structure
modeling. Boyle and Kim applied TO as an analytical tool to
compare different hip prostheses with the help of an enhanced
version of the design space optimization (DSO) method,
which is a specialized TO algorithm proposed by Kim and
Kwak [71, 72]. This was a reversion process of Wolff’s Law
of bone remodeling Campos to evaluate different hip prosthe-
ses. Andrade-Campos further improved the idea by taking into
account the contact condition with a penalty contact formula-
tion [73]. TO was used as a tool to obtain the density evolution
of bone and the distribution of osteointegration by considering
friction at the bone-stem interface. The TO algorithm was also
certified to be reliable for modeling the femur and
femur/implant structure in a study by Kutylowski et al.
[74]. In general, TO could act as an efficient tool to
design the hip stem prosthesis to reduce stress shielding
and provide more space for the bone graft. Besides, TO
could provide references for modeling the femur accord-
ing to the biomechanical state. In arthroplasty, there are
only a few studies that explore the other joint implants.
Peto et al. conducted a study regarding the TO of knee
joint implant in knee replacement surgery [75]. A tibial
intramedullary implant for an osteosarcoma patient was
designed and optimized by the TO method. Although
the maximum von Mises stress and displacement of
the newly designed implant with a weight reduction
were increased, this study provides direction for future
research about TO design of the knee joint implant.
Med Biol Eng Comput (2021) 59:1673–1689
3.1.3 TO design of global layout structure of spine implants
in spine surgery
It is estimated that more than 500,000 spine surgeries are
performed annually in the USA alone [76]. Interbody fusion
devices and spinal fixators are applied to manage spinal insta-
bility with minimally invasive surgical techniques. However,
severe complications such as subsidence, dislodgement, or
adjacent disc degeneration may affect the metallic implants
[77–79]. Many researchers have tried to obtain an optimum
design of interbody implants with the assistance of TO. The
lumbar interbody fusion cage, artificial lumbar intervertebral
disc, and spinal fixator device have been the research hotspots
in recent years. The new design was supposed to provide a
more rational distribution of mechanical stresses while maxi-
mizing the volume available for the bone graft.
TO design of the spinal fusion cage and artificial lumbar in-
tervertebral disc The spinal fusion cage and artificial lumbar
intervertebral disc used to be preferred substitutes for dam-
aged intervertebral discs or the fusion of adjacent vertebra.
In 2006, Zhong et al. designed a spinal fusion cage aiming
to maximize the global structural stiffness by decreasing the
volume of the implant [36]. The TO design was controlled by
the Ansys software. The newly designed cage also showed
better mechanical properties. Most studies about the global
layout of the spine implant followed the same routine to min-
imize strain energy with a volume or mass fraction constraint.
The decrease of strain energy led to better mechanical prop-
erties, while the reduced mass or volume permitted more graft
material and more space for tissue ingrowth. Jozef et al. car-
ried out further research based on Zhong’s study [80]. An
AM-fabricated poly-lactic-acid (PLA) cervical implant was
tested to determine whether it could withstand compressive
axial loading as a human vertebra. Although the test results
showed that TO-designed implant could not meet the demand,
the creation of the numerical static loading modeling method
could offer some helpful references for future research.
Biodegradable materials combined with bone grafts will also
be a mainstream trend in future bone tissue engineering re-
search. Wang et al. redesigned the macroscopic structures of
the crescent and flat-shaped cages (two commonly used
cages) using the TO method [81]. Although the TO cages
showed negligible influence to strain energy of cancellous
and von-Mises stress on the endplate, the reduced volume of
optimized cages provided more spaces for bone grafts that
would benefit bony fusion.
TO design of the fixation device between the lumbar verte-
brae Tovar et al. applied TO and the following shape optimi-
zation in their study [82]. A lumbar spine fixation implant was
redesigned by the TO method. The TO was formulated to
minimize strain energy by a mass fraction constraint with
Med Biol Eng Comput (2021) 59:1673–1689
the help of the Genesis software, and the following shape
optimization was performed using a grid perturbation ap-
proach by minimizing the mass subject to a maximum Von
Mises stress constraint. The two stages of optimization result-
ed in an available volume fraction for the bone graft material.
It was a typical case of multi-objective structural optimization.
Also, Lin et al. explored the rod-shaped dynamic spinal fixator
such as the Dynesys (DY) system [83]. DY is a type of dy-
namic fixator and has been used in the clinic for more than a
decade. It is designed to restore spinal stability and provide
flexibility. This study applied the TO Ansys software to de-
sign a new rod, aimed at minimizing strain energy and effec-
tively reducing stiffness. This TO-designed rod showed satis-
factory results. Except for the rod-like fixator, Chen and Shih
were interested in a new lumbar interspinous device [84]. The
following four FE spine models were compared: an intact
spine without an implant, implantation of the TO-designed
implant, the device for intervertebral-assisted motion (DIAM
system), and the Dynesys system. The results showed that the
TO-designed lumbar interspinous device performed better in
some respects than the DIAM and Dynesys systems. The
Coflex-F implant has been used to treat lumbar spinal stenosis
for a long time. Guo and Yin optimized the Coflex-F
design using the TO method and called it Coflex-NEW.
Except for the reduction in mass and volume, the max-
imum von Mises stress of the implant structure in dif-
ferent action processes was decreased. The von Mises
stress in the spinous process was also better distributed
than with the conventional Coflex-F implant [85].
We introduced the advances of the TO technique at the
level of the global layout structure in different orthopedic
fields in the above sections. The TO technique also benefits
oral medicine to get better biomechanical distribution at the
bone and dental implant sites. Chang et al. designed a new
dental implant at the first molar section of the maxilla with the
TO method [86]. Although the volume of the redesigned im-
plant was reduced, the biomechanical property was similar to
that of the traditional implant with lower displacement and
higher stiffness. Zhong et al. developed a novel topological
design for an all-ceramic dental bridge to minimize the frac-
ture incidence [87]. The BESO and extended FEM (XFEM)
algorithm were combined to attain the novel design; this meth-
od may be helpful for future studies. Seitz et al. used two TO
methods, namely SIMP and Soft-Kill Option (SKO), to pre-
dict the actual tooth-root shape [88].
Most of the abovementioned studies followed the same
process to seek more clinically beneficial and high-
performing material distribution of implants’ global layout
structure based on the TO design and then validated the new
designs by FEA or mechanical tests in vitro. Accordingly,
these studies had some limitations. First, all the above
methods were based on simple static loading conditions, when
in fact, dynamic loading conditions would more closely depict
1679
a real force situation. Second, to simplify the development and
use of the model, muscles and ligaments were not taken into
consideration. In some cases, muscle forces might have had
significant effects on stress distribution [89]. Third, more bio-
mechanical testing should be performed other than just FEA.
To accelerate the clinical application of TO, several animal-
experiment studies and clinical tests should be conducted.
3.2 Hierarchical TO design in orthopedic implants
As both the macro and microstructure can influence the me-
chanical property of implants, hierarchical TO also benefits
orthopedic implants. There are two stages of hierarchical TO:
TO design of global layout structure and TO of local micro-
structure [15]. The local microstructure refers to different po-
rous structures. The porous structure can reduce the obvious
mechanical mismatch between bone tissue and metallic im-
plants [90]. Many porous scaffold characteristics such as pore
location, pore size, pore interconnectivity, permeability, and
material surface chemistry are proven to influence tissue re-
generation [91]. An increasing number of research studies
about bone tissue engineering have combined the TO-
designed porous implant with a bio-activator to promote tissue
regeneration. The key feature of the porous microstructure is
the design of a “unit cell.” The structure of the “unit cell”
could be designed by image-based design approaches or
CAD [92–98]. These unit cells could also be designed using
the TO approach. The hierarchical TO design introduced both
local structure and global layout to achieve better implants.
Hierarchical research often follows the same process. Most of
the TO-designed material at the global layout level is
displayed by density values ranging from 0 to 1, where 0
refers to void and 1 refers to solid. Thus, the low-density area
was substituted by low-bulk modulus microstructures and the
high-density area was substituted by high-bulk modulus mi-
crostructures. In addition to the differences in bulk modulus,
TO-based research is also concerned with the number, loca-
tion, shape, size, and interconnection of the unit cells. In this
review, the restrictions were relaxed that any local porous
structure (unit cell designed by TO or other methods) filled
in the TO-designed global structure map were regarded as
hierarchical TO design. Besides, the porous structure obtained
by TO method would be emphatically expounded. In the next
sections, recently published studies are discussed to exhibit
more clinical applications of hierarchical TO design in
orthopedics.
3.2.1 Hierarchical TO design of the implant in trauma surgery
and maxillofacial surgery
In trauma surgery, the TO-designed fixation plate with the
global layout structure mentioned above (Section 3.1.1)
showed better mechanical properties than the hierarchical
1680
TO design. As for the hierarchical TO design of the ORIF
plate, Gogarty and Pasini designed the fixation plate using
the hierarchical TO technique [99]. The multi-objective opti-
mization and multi-scale TO were integrated to design the 2D
plate. Target-matching TO was applied to obtain unit cells
with desired stiffness and maximum permeability throughout
the implant. In their study, another two gradient-based opti-
mization procedures combined with SIMP were applied to
achieve the optimal implant. The hierarchical TO technique
resolved the conflict between mechanical support properties
and mass transport properties. It is well known that the obvi-
ous limitations of the variable density method were unaccept-
able checkerboard patterns of the model [100]. Hence, a more
effective filtering technique was required, especially at the
unit cell level. In Fig. 3, exhibited is a descriptive flowchart
of a typical hierarchical TO design case of the fixation plate
[99]. In 2019, a new lattice plate was designed by Jia based on
TO [101]. The local structure of the newly designed plate was
composed of regular tetrahedrons based on the TO-designed
global layout structure. This was because the regular tetrahe-
dron intrinsically has balancing geometric characteristics to
provide enough stability for the lattice plate structure. The
newly designed lattice plate improved the stress of the skele-
ton and reduced the stress shielding effect of the plate. In
maxillofacial surgery, a personalized mandibular implant is
Fig. 3 A typical hierarchical TO
design case of the fixation plate
reported by Gogarty E et.al [99].
(a) The initial fixation plate. (b)
The initial TO result of global
layout structure. (c) CAD
representation of the optimized
implant. (d) The initial optimized
unit cell. (e) CAD representation
of the optimal unit cell
Med Biol Eng Comput (2021) 59:1673–1689
an important topic of discussion. Cheng carried out a TO
method-based study on canine teeth about the personalized
porous mandibular implant. The shape of the supporting part
of the implant was obtained through TO [102]. A “porous
unit” with a 600-mm pore size and square shape was selected
to fill the TO-designed implant as these porous structure char-
acteristics seemed suitable for orthopedic implants
manufactured by AM [103]. Hu et al. also optimized the man-
dibular graft with porous scaffold structure through the TO
approach [104]. Different from Cheng’s research, the mandib-
ular graft was divided into two parts called the “shell” and
“core” [102]. The function of the “shell” was to maintain the
original shape of the bone defect, while the core was defined
as the design domain of the TO. Any unwanted material of the
core was removed after TO. An irregular porous-like structure
with “holes” would then be obtained. Through biomechanical
testing, both Cheng and Hu’s new TO-designed implants
showed better biomechanical behavior than the original im-
plants or implants with regular unit pore. Figure 4 illustrates
the major research activities about the TO design of the im-
plant in trauma surgery and maxillofacial surgery behind this
research program. The models presented as an example in Fig.
4 were from the research of our team about the TO design of
the three-dimensional printed plate which was used as tibial
fracture internal fixation plate on experimental rabbits.
Med Biol Eng Comput (2021) 59:1673–1689
Fig. 4 The TO design and verified experiments of the internal fixation
plate for tibia fracture in rabbits. (a) The load condition simulation of the
rabbit’s tibia in finite element model after ORIF. (b) The FEA of the
rabbit’s tibia after ORIF. (c) The TO design and verified experiments:
3.2.2 Hierarchical TO design of hip joint prosthesis
in arthroplasty
Regardless of the application of global layout or local struc-
ture, the TO-based design of hip joint prosthesis has always
been the focus of research. Arabnejad Khanoki and Pasini
explored the hierarchical topology design of a 2D hip prosthe-
sis [105]. One implant with a novel microstructure was de-
signed based on the TO method and fabricated by rapid
prototyping. Despite some study limitations such as variable
loading design and the accuracy of microscopic stress, they
presented a novel methodology integrating multiscale analysis
and created a novel process to optimize the structure of hip
prosthesis. Compared with the fully dense titanium implant,
the cellular implant showed markedly reduced bone resorption
and maximum value of interface stress. This methodology
may be the trend for future implant designs to reduce clinical
complications of current implants. In 2018, He et al. extended
the hierarchical TO idea from a 2D structure to a 3D hip
prosthesis [106]. They optimized the global layout structure
with the help of the Hyperworks software. The TO technique
determined the material macroscopic distribution; next, face
and body-centered cubic with vertical struts (FBCCZ) unit
cells were taken to replace the semi-dense regions. FEA re-
sults showed satisfactory regional compliance and lower stress
shielding than the generic implant. The newly designed hip
prosthesis was fabricated by 3D printing to prove its manu-
facturability. This research was a classic case of how TO was
changed from the concept design into an actual design. Most
researchers follow the same process wherein the global layout
1681
① TO design of global layout structure; ② the post-processing to smooth
the original TO-designed model; ③ TO design of local structure; ④ the
verified experiment with FEA method; ⑤ mechanical test; ⑥ cell exper-
iment in vitro; ⑦ the verified experiment in vivo
structure was designed by TO and the local microstructure
was filled with different porous structures according to the
TO result of different material distribution “density.” The
TO design of the hip stem is depicted in Fig. 5. The models
presented in Fig. 5 were from the research of our team about
the TO design of hip stem based on Synergy prosthesis (Smith
& Nephew, USA).
3.2.3 Hierarchical TO design of the interbody fusion devices
in spine surgery
Interbody fusion cage made of titanium Hierarchical TO was
widely used in the design of the interbody fusion cage for the
treatment of spinal instability. Titanium was one of the most
common materials in spine implants. Initially, the researchers
focused on titanium as the material of the spine implant. Lin
et al. redesigned an interbody fusion cage using hierarchical
TO [107, 108]. They noted that the density of the global layout
served as a reference to assign the microstructural topology.
As for the microstructure, the target stiffness tensor under
different material densities determined by the TO result of
the global layout structure was set as the basic goal of micro-
structural TO. A constraint on volume fraction was imposed to
ensure that scaffold possessed desired porosity. Chahine G
et al. reported this TO method of microstructure, which is
shown in Fig. 6 [13, 109]. The entire cage design could be
generated by duplicating the periodic microstructures within
the global density layout. Hollister concluded this study as
Fig. 7 [110]. The new design could provide equivalent or
better stability than conventional cage designs, while lowering
1682 Med Biol Eng Comput (2021) 59:1673–1689

Fig. 5 The TO design routine of the hip stem. a, b: CAD model of hip design the global layout structure of the hip stem. d: Different porous
stem, 3D reconstruction of femur geometry from CT. c: A standard structures were placed in the local structure of the hip stem according to
femoral neck resection was mimicked and the implant was positioned the TO results
into it. FEA (①), TO (②), and post-processing (③) were performed to

subsidence and stress shielding risk. To address the pore con- properties [111]. They overcame the problem of topology de-
nectivity of the porous structure, Lin et al. developed an sign not being able to ensure pore connectivity, by adding a
image-based optimization scheme that could adjust the scaf- connectivity filer in the design procedure. The connectivity
fold microstructure to achieve customized native tissue elastic filer would force the optimizer to assure the pore connectivity

Fig. 6 TO process of the local

structure, obtaining the 1/8th unit
cell and unit cell after Boolean
operation with different porosity
designed by Xu et al. [109]. The
objective function was the maxi-
mum structure stiffness under the
constraint function of porosi-
ty(40%, 50%, 60%, 70%, and
80%). The material distribution
corresponding to different poros-
ity could be obtained. The
Solidwork (Dassault Systemes,
Concord, MA) was used to gen-
erate the geometry model accord-
ing to the porosity cloud, and a 1/
8th unit cell in open-cell configu-
ration with different porosity
could be obtained. Magics 21.0
(Materialise, Belgium) was used
to repair and smooth the surface
of the 1/8th unit cell. A complete
unit cell was obtained by the
Boolean operation of the 1/8th
unit cell
Med Biol Eng Comput (2021) 59:1673–1689
Fig. 7 Hierarchical TO design procedure of the interbody spine fusion
cage [107, 110]. (a) A global design domain is created between the
vertebral bodies (in the white circle). (b) A global-level topology optimi-
zation under physiologic loads leads to a global material distribution
within the design domain. (c) A microstructure TO creates specific porous
in the microstructure. The newly designed implant achieved
the desired mechanical performance while providing intercon-
nected channels for bio-factor delivery. Moreover, sufficient
porosity for bio-factor delivery was also provided. They fur-
ther operated the structural and mechanical evaluations for the
optimized cages made of titanium to verify their newly de-
signed cage [112].
Interbody fusion cage made of biodegradable material In
2005, Hollister et al. introduced the material of interbody fu-
sion cage as a new topic as novel research [113]. Of signifi-
cance, they introduced the hierarchical TO methods into bone
tissue engineering. Two significant breakthroughs should be
mentioned: First, biodegradable poly(propylene fumarate)/β-
tricalcium phosphate (PPF/β-TCP) composites substituted the
scaffold material Ti alloys. Second, the TO scaffold was com-
bined with ex vivo gene therapy in mice subcutaneously. The
combination of the TO design with osteoconductive biode-
gradable polymer composite can fulfill the goal of load-
bearing at the initial stage as a suitable tissue-engineering
strategy. The TO design may enhance the mechanical perfor-
mance of bone tissue engineering implants, while the micro-
structure may benefit bone regeneration. To solve the conflict
between the diffusivity and bulk modulus of implants, Kang
et al. found another innovative approach, wherein they set the
mass transport (diffusivity) and mechanical (bulk modulus)
cross-property bounds as the optimization objective, using
SIMP [114]. The nonlinear sensitivity filter proposed by
Sigmund to avoid numerical instabilities was inserted into
the TO process [115]. Next, they validated their ideas by a
biodegradable interbody fusion cage for spinal fusion [116].
Its global material density map was obtained by TO of global
1683
microstructures that are maximally stiff but match the porosity predicted
from the global-level optimization. (d) The final scaffold is created by
Boolean intersection of the global and architecture-level design image
databases. (e) Actual scaffold built from titanium using a selective laser
melting process
anatomic structures to minimize compliance, following which
the microstructures with appropriate properties were deter-
mined by local microstructure optimization. Compression
tests and computational analysis revealed that this optimiza-
tion technique could be utilized to balance the complex re-
quirements of load-bearing, stress shielding, and interconnect-
ed porosity when using biodegradable materials for fusion
cages. One issue that must be taken into consideration is that
biodegradable materials are less stiff than Ti alloys, and the
stiffness of biodegradable materials will gradually reduce over
time. There is a strong possibility that biodegradable materials
may lead to treatment failure in the early period. To overcome
this problem, Lin et al. proposed a new method to coordinate
the imbalance between degradation and tissue reconstruction
rate [117]. Both time and degraded base stiffness weighting
factors were linearly superposed to get a different density dis-
tribution. The density distribution was created by selecting
time points during degradation. A degradable spine interbody
fusion cage device made of (PPF/β-TCP) was designed to
successfully maintain homologous stiffness. The mechanical
properties won out both the non-weighted and the convention-
al designs. To evaluate these degradable devices, Knutsen
et al. explored the static and fatigue properties of these novel
cages based on current American Society for Testing and
Materials (ASTM) testing standards [118, 119]. The cages
were designed by an image-based topology and fabricated
by 3D printing with poly(ε)-caprolactone (PCL). The ASTM
standards were designed prior to novel cages; hence, advanced
methods were carried out to provide more accurate and reli-
able results in the future. Liu et al. reported excellent fatigue
properties in TO-designed porous commercial-purity titanium
structure on account of its reduced stress concentration [120].
1684
Table 1 The comparisons of TO methods between global layout and local structure
Design Domain Method
Global Layout Structure Variable Density Method (SIMP model)
Evolutionary Structural Optimization (ESO)
Independent Continuous and Mapping Method (ICM)
Local Structure Variable Density Method (SIMP model)
Method of Moving Asymptotes (MMA)
The methods of TO design both in global layout and in
local structure in orthopedic implant showed huge advantages.
The comparisons of details were concluded by us in Table 1.
As illustrated in the table, one representative research was
selected as a reference for each TO method. Hierarchical TO
developed rapidly on account of its better mechanical proper-
ties and benefits to bio-factor delivery. The implant materials
developed from metallic to biodegradable biomaterial.
Different filters or weight factors were added to improve the
TO methods. Research explorations regarding the local micro-
structure’s “unit cell” gradually increased. The AM technique
overcame the limitation of conventional manufacturing, and
bio-additive manufacturing may develop gradually to achieve
the distribution of different biological materials [121]. FEA
and in vitro and in vivo tests were carried out to validate the
advantages of TO designs and even the improved perfor-
mance of the newly designed implants [122].
4 Challenges and prospects
With the rapid development of interdisciplinary research,
TO combined with AM technology can be a powerful tool
for orthopedic implants and bone tissue engineering based
on FEA. According to recent research studies, prospects
and challenges can be summarized as follows. First, most
researchers merely focused on the FEA, TO, and mechan-
ical testing. Only a few studies validated the biological
properties by conducting in vivo or in vitro experiments.
Plenty of experiments in vivo and clinical tests should be
performed before clinical application. Second, among the
majority of research studies, bone FE models are simpli-
fied with homogeneous mechanical properties, which is
inconsistent with the natural bone tissue. Exploring het-
erogeneous properties should be the trend of future stud-
ies. Multi-materials should be considered in different re-
gions of the TO-designed implants, especially the degrad-
able material. Studies about the balance of degradation
rate and bone growth rate may have important signifi-
cance for bone fusion. Third, the linear analysis of the
FEA method without considering the friction between
Med Biol Eng Comput (2021) 59:1673–1689
Objective Function & Constraints
Minimum compliance& Decrease the volume [30]
Minimum stresses & Increase or decrease the volume [70]
Minimum mass & Decrease the stress [82]
Multiple objective functions & volume fraction/porosity [107];
Effective bulk modulus and diffusivities & porosity [62]
Stiffness tensor & Volume fraction/porosity [111]
the bone-implant interface will also be replaced by the
method of nonlinear analysis. In addition, the combina-
tion of multi-objective structural optimization with the
hierarchical TO technique may be the future direction of
implant design. Furthermore, the dynamic loading condi-
tion should be the main trend of future research, and more
effective and appropriate filters and weight factors in TO
procedure should be parallelly developed in the medical
and industrial fields to meet the demand of the unit cell
design. Last, the database of TO unit cells for porous
structure according to the specific porosity and anatomical
site should be completed to satisfy the different require-
ments of different implants.
In this review, we summarized the current advances of TO
technique in orthopedic implants. In addition, we separately
discussed the better mechanical and bio-factor delivery func-
tion of novel designed implants at the level of global layout
and hierarchical structure. Last, we proposed likely challenges
and predicted the directions of future research.
Author contributions The idea was come up with Jincheng Wang and
Qing Han. The first draft of the manuscript was written by Naichao Wu.
The literature search was performed by Shan Li and Boyan Zhang. This
review was revised by Qing Han, Chenyu Wang, and Bingpeng Chen. All
authors commented on previous versions of the manuscript and approved
the final manuscript.
Funding This work was supported by (1) the National Natural Science
Foundation of China (grant numbers 82072456&81802174), (2) the
National Key R&D Program of China (No. 2018YFB1105100), (3) the
Department of Science and Technology of Jilin Province, P.R.C. (grant
numbers 20200404202YY&20200403086SF&20200201453JC), (4) the
Department of finance in Jilin province (grant
number2019SCZT046&2020SCZT037&201817294302), (5) the
Undergraduate teaching reform research project of Jilin University (grant
number 4Z2000610852), (6) the Key training plan for outstanding young
teachers of Jilin University (grant number 419080520253), (7) the
Bethune plan of Jilin University (grant number 470110000692), and (8)
the Jilin Province Development and Reform Commission, P.R.C.
(grant numbers 2018C010).
Declarations
Conflict of interest The authors declare no competing interests.
Med Biol Eng Comput (2021) 59:1673–1689
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Publisher’s note Springer Nature remains neutral with regard to jurisdic-
tional claims in published maps and institutional affiliations.
Naichao Wu , M.M., a resident
doctor of the Second Hospital of
Jilin University. His research in-
terests include finite element anal-
ysis and topology optimization
design of implants in orthopedics.
Med Biol Eng Comput (2021) 59:1673–1689
Shan Li , M.M., a resident doctor
of the Second Hospital of Jilin
University. Her research interests
include integrated analysis of
gene variants and artificial intelli-
gence.
Boyan Zhang , Ph.D., a resident
doctor of the Second Hospital of
Jilin University. His research in-
terests include integrated analysis
of gene variants and genetic func-
tion in bone and cartilage devel-
opment.
Chenyu Wang , Ph.D., a doctor
of the Second Hospital of Jilin
University. Her research interests
include additive manufacturing
technology and tissue engineer-
ing.
1689
Bingpeng Chen , Ph.D., a deputy
chief physician of the Second
Hospital of Jilin University. His
research interests include additive
manufacturing technology and
digital orthopedics.
Qing Han , Ph.D., a deputy chief
physician of the Second Hospital
of Jilin University. His research
interests include additive
manufacturing technology, medi-
cal imaging, and digital orthope-
dics.
Jincheng Wang , Ph.D., a chief
physician of the Second Hospital
of Jilin University. His research
interests include additive
manufacturing technology, digital
orthopedics, and tissue engineer-
ing.