Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Contents lists available at ScienceDirect

Journal of the Mechanical Behavior of

Biomedical Materials
journal homepage: www.elsevier.com/locate/jmbbm

Bioinspired surface functionalization of metallic biomaterials T

a,b,c a a,d,⁎ c e
Yingchao Su , Cheng Luo , Zhihui Zhang , Hendra Hermawan , Donghui Zhu ,
Jubin Huanga, Yunhong Lianga,d, Guangyu Lib, Luquan Rena
a
Key Laboratory of Bionic Engineering, Ministry of Education, Jilin University, 5988 Renmin Street, Changchun 130025, China
b
Key Laboratory of Automobile Materials, Ministry of Education, College of Materials Science and Engineering, Jilin University, 5988 Renmin Street, Changchun 130025,
China
c
Department of Mining, Metallurgical and Materials Engineering & CHU de Québec Research Center, Laval University, Québec City, Canada
d
State Key Laboratory of Automotive Simulation and Control, Jilin University, 5988 Renmin Street, Changchun 130025, China
e
Department of Biomedical Engineering, University of North Texas, Denton, TX 76207, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Metallic biomaterials are widely used for clinical applications because of their excellent mechanical properties
Metallic biomaterials and good durability. In order to provide essential biofunctionalities, surface functionalization is of particular
Bioinspired surface functionalization interest and requirement in the development of high-performance metallic implants. Inspired by the functional
Biocompatibility surface of natural biological systems, many new designs and conceptions have recently emerged to create
Biofilm resistance
multifunctional surfaces with great potential for biomedical applications. This review firstly introduces the
Corrosion resistance
metallic biomaterials, important surface properties, and then elaborates some strategies on achieving the
Wear resistance
bioinspired surface functionalization for metallic biomaterials.

1. Introduction
Metallic biomaterials are widely used for clinical applications due to
an excellent combination of mechanical properties and durability when
compared to the ceramic and polymeric biomaterials. However, they
still lack satisfactory biofunctionalities for certain applications, such as
blood compatibility for blood-contacting devices, bone conductivity in
orthopaedic applications, and ultra-high wear and corrosion resistances
for joint replacement. When a metallic biomaterial is implanted into the
living tissue, the surface properties of the material play critical roles in
the interactions between the biological environment and the implant
(Nel et al., 2009; Planell et al., 2010). Therefore, surface functionali-
zation is of particular interest and requirement to improve surface
bioactivity and other biofunctionalities and hence enhance the cellular
and tissue responses.
The morphology and properties of biological materials and struc-
tures have been developed by nature over millions of years, exhibiting
unique characteristics and almost perfect functions to adapt to the
harsh environment (Koch et al., 2009), such as the self-cleaning prop-
erty of lotus leaves (Barthlott and Neinhuis, 1997), the structural colour
(Kolle et al., 2010) and light trapping effect (Han et al., 2012) of but-
terfly wings, the superior combination of strength and toughness of
bone tissue (Launey et al., 2010; Ritchie, 2011), and plastron property
for underwater breathing (Shirtcliffe et al., 2006). These natural
functions and strategies have recently emerged as a new source of in-
spiration to create multifunctional surfaces with high potentials to
apply on the biomaterials. Many reviews have been published on
bioinspired surfaces with special wettability for various applications
(Wang et al., 2015; Liu et al., 2010; Yao et al., 2011; Zhang et al.,
2008a; Shin et al., 2016; K Webb et al., 2011), but few addressed the
other surface functions inspired by nature and their development on
metallic biomaterials.
In this review, we focus on the functionalization strategy of bioin-
spired surface and their application on metallic biomaterials. Section 2
generally presents the inert metals and biodegradable metals for bio-
medical application. Section 3 introduces the relations between the
surface properties and the cellular and tissue response. Before arriving
into conclusion, Section 4 discusses the significant functionalization of
bioinspired surfaces which have been or potentially be applied on
metallic biomaterials using tailored morphology, chemistry, and wett-
ability.
2. Metallic biomaterials
The record of metal's exploitation for biomedical applications can be
traced back to 200 A.D. when the early European integrated an iron
dental implant into human bone (Ratner et al., 2004). Compared to
polymers and ceramics, metals can provide a combination of required

⁎
Corresponding author.
E-mail address: zhzh@jlu.edu.cn (Z. Zhang).

http://dx.doi.org/10.1016/j.jmbbm.2017.08.035
Received 31 January 2017; Received in revised form 23 August 2017; Accepted 29 August 2017
Available online 01 September 2017
1751-6161/ © 2017 Elsevier Ltd. All rights reserved.
Y. Su et al.
Fig. 1. Contact angles showed increased hydrophilicity on (a) flat, (b) nanometer and (c) sub-micron surface-featured titanium. (d) Adhesion density showed that sub-micron structures
led to the best adhesion density (seeding density was 3500 cells/cm2), and cell aspect ratios showed oriented cell morphology for flat, nanometer and sub-micron structures (increased
right to left). Note that cell aspect ratios were calculated by the length of a single cell divided by its width (inset image of (d)). All error bars are mean ± SEM; n = 3; *p < 0.01 (compared
to R-2) and **p < 0.05 (compared to R-1) Khang et al. (2008).
properties for the biomedical application, including the high ductility
and fatigue limit, good corrosion and wear resistance. Metallic bio-
materials account for approximately 70% implants including ortho-
paedic (knee joint, total hip joint, bone plates, fracture fixation wires,
pins, screws, and plates) and cardiovascular (artificial heart valves,
vascular stents, and pacemaker leads) (Niinomi et al., 2012).
Up to now, the three most used metallic biomaterials are stainless
steels (SS), cobalt-chromium (Co–Cr) alloys and titanium (Ti) alloys
(Niinomi et al., 2012). The 316 L type SS (SS316L) is the most widely
used metal mainly for non-permanent implants such as bone plates and
screws, whilst the more corrosion resistance Co–Cr- or Ti-alloys are
used for permanent ones such as hip implants. The concern of nickel
toxicity in SS316L has led to the development of a nickel-free high-
nitrogen SS as a promising replacement in future for orthopaedic and
cardiovascular stent applications. This new alloy has been proven to
possess improved biocompatibility combined with excellent corrosion
and wear resistance (Talha et al., 2013). Co–Cr alloys, mainly re-
presented as Co–Cr–Mo and Co–Cr–W–Ni series, are characterised by
their high corrosion and wear resistances (Yan et al., 2007). They have
been used for making various implants such as artificial joints, denture
wires, and stents (Narushima et al., 2013). Pure Ti and Ti–6Al–4 V have
been used in orthopaedic and dental applications owing to their su-
perior biocompatibility, pitting corrosion resistance and high strength
to weight ratio to SS and Co–Cr alloys (Gepreel and Niinomi, 2013). A
number of β-type Ti alloys with nontoxic and allergy-free elements and
low Young's modulus (35–80 GPa) have been developed to avoid the
harmful elements present in Ti–6Al–4 V and the stress shielding effect
(Lin et al., 2016).
Apart of the three mentioned metals, biodegradable metals have
been developed as ideal materials for temporary implants. They are
expected to degrade safely in the body after fulfilling their function,
thereby avoiding the need for removal surgery, accelerating the healing
process, reducing risks from permanent presence of the implant, and
eventually reducing overall hospitalisation time and costs (Zheng et al.,
2014). Among the three most studied biodegradable metals (magne-
sium, iron, zinc), magnesium and its alloys are advancing to commer-
cial products (Zheng et al., 2014; Zhu et al., 2017; Ma et al., 2016a,
2015a). They possess similar physical and mechanical properties to
those of bones, i.e. Young's modulus, making them suitable for ortho-
paedic applications (Staiger et al., 2006). Magnesium alloys usually
corrode too quickly in the human body, but various improvements have
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Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
been made to retard its fast degradation, such as by using high purity
Mg, proper alloying elements, composite structure, nanocrystalline and
amorphous microstructure, and surface modification (Dorozhkin, 2014;
Shadanbaz and Dias, 2012; Hornberger et al., 2012). Recently, a long-
term clinical study found that the controlled degradation of an Mg-Zn-
Ca alloy resulted in the formation of a “biomimicking calcification
matrix” at the degrading interface to initiate the bone formation process
(Lee et al., 2016).
3. Surface properties
When a metallic biomaterial is implanted into the living tissue, an
interface is created between the implant material and the surrounding
tissues. It is of significance to ensure the implants with specific surface
features be recognised by the highly precocious ability of biological
systems at the implant–tissue interface (Nel et al., 2009; Planell et al.,
2010). The implant surfaces with different morphology, chemistry, and
wettability will strongly influence the material-cell interaction and
thereby tissue integration at the interface.
3.1. Surface morphology
The morphological features such as surface roughness (Deligianni
et al., 2001) and its topography (Khang et al., 2008) can strongly in-
fluence the protein adsorption (Deligianni et al., 2001), cell adhesion
(Khang et al., 2008), cell migration and differentiation (Zinger et al.,
2005a). Generally, surface roughness can affect cell behaviour directly
via enhanced formation of focal contacts or indirectly through selective
adsorption of serum proteins required for cell attachment (Deligianni
et al., 2000). The substratum topography with different scales and
features have a direct effect on the abilities of cells to produce orga-
nised cytoskeletal arrangements (Shen et al., 2015). It has been re-
ported that the adhesion and proliferation of vascular and bone cells
increased on nanometer-scaled surfaces, as shown in Fig. 1 (Khang
et al., 2008), nonetheless a few reports did not confirm such significant
correlations (Izquierdo-Barba et al., 2015; Bagherifard et al.,
2015). Bagherifard et al. (2015) suggested to consider additional
roughness parameters, e.g. surface irregularities formation and their
spatial distribution, to fully describe the precise surface morphological
features. Moreover, it must be mentioned that cellular response to
substratum topography may be different from one cell type to another.
Y. Su et al.
For example, on the severe shot peened surface of SS316L, the osteo-
blasts cell could maintain their proliferation and adhesion functions,
while the gram-positive bacteria showed a significantly reduced adhe-
sion (Bagherifard et al., 2015).
3.2. Surface chemistry
The surface chemistry of a metallic biomaterial can be altered to
induce cell adhesion and spreading (Roach et al., 2007). Many studies
have demonstrated that surface functional groups can affect protein
adsorption and subsequent cellular responses (Thevenot et al., 2008). In
general, hydrophilic functionality provides a low interfacial free energy
resulting in reduced protein adsorption, cell adhesion, and blood
compatibility (Wang et al., 2004). As for metallic biomaterials, the
adequate and well-adhering surface oxide layer can improve the bio-
compatibility of medical devices via changing the protein adsorption
(Silva-Bermudez and Rodil, 2013), and different chemical compositions
of the different phases and grain boundaries may also have different
interactions with cells (Geetha et al., 2009).
3.3. Surface wettability
The protein adsorption that leads to cell attachment can be con-
trolled by surface wettability. Wetting on the implant surface by the
physiological fluid is the foremost event during the implantation (Paital
and Dahotre, 2009). It is well established that proteins tend to bind
onto hydrophobic surfaces, and cells typically adhere selectively on the
hydrophilic regions, although the cell behaviour is also dependent on
the cell type and the material (Arima and Iwata, 2007). Generally, few
cells can adhere to superhydrophobic surfaces where cells typically
adopt a round morphology upon attachment (Song and Mano, 2013).
Surface wettability can be preferentially tuned from hydrophobic to
hydrophilic through controlling surface chemistry and topography (Lai
et al., 2013), so it is difficult to discuss the effect of wettability without
considering these two factors. For example, L929 cell attachment was
studied with varying surface wettability of hexamethyldisiloxane
modified by plasma polymerization followed by O2 plasma treatment
Fig. 2. SEM of L929 attached to surfaces with different wettability in 24 h in low magnification (top, original: 500×) and high magnification (bottom, original: 3000×) (Wei et al.,
2007).
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Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
(Wei et al., 2007), as shown in Fig. 2. It can be observed that the hy-
drophilic surface has more cells attached as compared to the hydro-
phobic surface after 24 h of incubation. The decrease of the contact
angle results from the introduction of more hydrophilic –COOH groups
and the reduction of more hydrophobic –CH3 groups on the surface
(Wei et al., 2007).
4. Bioinspired surface functionalization
To fulfil the different clinical requirements, various synthetic
functionalization methods (mechanical, chemical and physical) on
metallic biomaterials have been proposed and reviewed in previous
studies (Hornberger et al., 2012; LIU et al., 2004). In addition to these
methods, there are fascinating strategies developed by nature over
millions of years to exhibit almost perfect multifunctional surfaces
(Koch et al., 2009). The biological materials and structures, dictated by
the evolution, environmental constraints, and the limited availability of
materials, have unique characteristics that distinguish them from syn-
thetic counterparts. These natural functions and strategies have re-
cently emerged as a new source of inspiration to create multifunctional
surfaces with high potentials to apply on biomaterials. Therefore, in the
following sections, various functionalizations of metallic biomaterials
using bioinspired surface technologies are discussed.
4.1. Osteointegration
In the case of bone implants, it is generally accepted that osteo-
progenitor cells migrate to the implant site and differentiate into os-
teoblasts that make bone. The requirement for biocompatibility is that
the material should integrate with the bone, i.e. osteointegration
(Hallab and Jacobs, 2013). Stainless steel and Ti alloys have been
commonly used in clinics for fracture fixation, and new bone formation
can be observed on the surface of the fixation devices, especially those
made of Ti alloys. The native TiO2 layer minimises the metallic ion
release and adverse body reactions, and thus improve the biocompat-
ibility of Ti alloys (Lorenzetti et al., 2015; Wang et al., 2016). However,
this native passive oxide layer does not render the required
Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 3. (a) The existing hierarchical structure in rat's native alveolar bone tissue. (i) Macro image at low magnification SEM; the insert is the image of pathological section with
hematoxylin and eosin stain (the blue arrows indicated haversian canal, 0.5–2 µm). (ii) SEM and AFM image of microscale pit-like unit. (iii) SEM and AFM image of nanoscale
electrospinning-like unit. (b) Illustration and contact mode AFM images of three different Ti substrate surfaces. (c) Fluorescence microphotographs of osteoblastic cells adhesion on the
corresponding specimens during 48 h of incubation (Wang et al., 2013).

osteointegration (Liu et al., 2004), so various surface functionalization
methods have been proposed to improve the bone conductivity or
bioactivity.
4.1.1. Micro/nano structured surface
The surface properties such as morphology, roughness and wett-
ability have been known to influence osteoblast responses to Ti implant
(Rosales-Leal et al., 2010). Zinger et al. found that micron-scale and
submicron scale topographies on Ti implant could promote osteoblast
differentiation and osteogenic local factor production (Zinger et al.,
2005b). There is a synergistic effect between high surface energy and
topography of Ti substrate, while both micron-scale and submicron
scale structural features are necessary for this synergistic response of
osteoblasts (Zhao et al., 2007). A combined hierarchical structure
composed of micro-pits interlaced self-assemble TiO2 nanotubes was
recently developed on a Ti surface (Fig. 3b) by taking the inspiration
from the natural hierarchical micro/nano structure in rat's alveolar
bone (Wang et al., 2013). The tightly arrayed self-assembled TiO2 na-
notubes with a diameter range of 30–50 nm on the bioinspired surface
were close to collagen fibres of 60–80 nm within rat's mandible
(Fig. 3a). The larger surface energy and preferable hydrophilicity of the
bioinspired micro/nano surface can provide superior attachment and

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Y. Su et al.
growth of osteoblasts and thus better bioactivity and biocompatibility,
as compared to the smooth and purely micro-treated counterparts
(Fig. 3c). This bioinspired micro/nano fabrication on metallic implant
has been applied successfully in a clinical trial for 12 months (Huang
et al., 2015) and provides a new strategy for osteopathic application of
metallic biomaterials.
4.1.2. Calcium phosphate coating
Calcium phosphate (CaP) ceramics, such as tricalcium phosphate
(TCP), hydroxyapatite (HA) and dicalcium phosphate dihydrate
(DCPD), have been clinically used in orthopaedic surgery due to their
intrinsic bioactivity and biocompatibility (LeGeros, 1990). CaP coatings
were developed onto the surface of metallic implants to combine the
mechanical strength of metals with the excellent biological properties
of CaP ceramics. It has been well-recognised that CaP coatings can lead
to faster biological fixation and better clinical success rates in the long-
term than uncoated implants due to the superior initial rate of os-
seointegration (Surmenev et al., 2014). Many methods have been de-
veloped to deposit CaP coatings on metal implants including plasma-
spraying, biomimetic precipitation, sputtering, sol–gel, electrophoretic
and electrochemical deposition, and ion beam dynamic mixing de-
position (Dorozhkin, 2014). The plasma-spraying coating method has
already been used on Ti dental implants in clinical practice, due to its
high deposition rate and the ability to coat a large area (de Jonge et al.,
2008). However, the plasma-spraying coating has some serious con-
cerns, such as the poor adhesion of the thick coating, phase change
during the high-temperature coating process, and particle release and
delamination during the clinical application (Yang et al., 2005).
In order to overcome these drawbacks, the biomimetic precipitation
has drawn more attention when compared to the other methods.
Inspired by the natural CaP mineralisation process, the precipitation
process is conducted in a physiological environment at low tempera-
ture, resulting in a biologically identical coating to bone apatite
(Oliveira et al., 2003). For example, a homogeneous bone-like carbo-
nated apatite (BCA) biomimetic coating was applied to dense Ti-6Al-4 V
alloys and porous Ta cylinders (Fig. 4a), by immersion into simulated
body fluid at 37 °C and then at 50 °C for 24 h (Barrere et al., 2003). The
in vivo implantation test in the femoral diaphysis of adult female goats
showed that the bone contact was always found significantly higher for
BCA-coated implants than the corresponding non-coated ones (Fig. 4b),
which indicates that the BCA coating enhances the bone integration of
Fig. 4. (a) ESEM micrographs of non-coated and BCA-coated Ti6Al4V (grit-blasted) and porous Ta. (b) Nondecalcified histological sections of the corresponding dense Ti6Al4V implants
(at magnification 40 ×) and porous Ta implants (at magnification 100 ×). All photos have been taken in the cortical bone region and thus at approximately similar locations, that is, the
edge of implants. The black zone corresponds to the implant and the purple zone corresponds to bone. wb indicates woven or de novo bone. Stain: methylene blue and basic fushin (Barrere
et al., 2003).
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Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
the two metals. Vaquette et al. (2013) extended the biomimetic CaP
coating application onto a polycaprolactone melt electrospun scaffold
and an accelerated osteogenic process was found on ectopic bone for-
mation in a subcutaneous rat model.
4.1.3. Organic biomolecule coating
Biomolecule surface functionalization on metallic biomaterials uti-
lises purely organic components of bone to enhance bone regeneration
in the clinical practice, such as extracellular matrix proteins (e.g. col-
lagen) or peptide sequences for bone cell adhesion (Hinderer et al.,
2016; Zhao and Zhu, 2014), and bone growth factors for new bone
formation (Ronga et al., 2013). In the preclinical studies other com-
ponents were used, such as deoxyribonucleic acid (DNA) for structural
reinforcement (van den Beucken et al., 2007), enzymes for bone mi-
neralisation (Douglas et al., 2014). Three major methods (physical
adsorption, physical barrier entrapment, and covalent attachment)
have been used to immobilise biomolecules onto Ti surfaces (de Jonge
et al., 2008).
In addition to these organic components of bone, it has been showed
preclinically that the self-polymerization mussel-inspired poly-
dopamine could be used to form a thin and surface-adherent coating
onto a wide range of inorganic and organic materials (Lynge et al.,
2015; Lee et al., 2007). Mussels are promiscuous fouling organisms and
can attach onto virtually all types of materials, including “non-ad-
herent” poly(tetrafluoroethylene) (PTFE), because of the rich content of
3,4-dihydroxy-L-phenylalanine (DOPA) and lysine amino acids found in
the foot protein of mussels (Fig. 5a) (Lee et al., 2007). The poly-
dopamine coating can also serve as a versatile platform for subsequent
surface-mediated reactions to further enhance the cell-adhesive, os-
teoconductive, and osteoinductive performance of Ti implants. For ex-
ample, Arginylglycylaspartic acid (RGD)-conjugated polymers, HA na-
noparticles, and bone morphogenic protein-2 (BMP-2) were added
during the polymerization process of polydopamine coating (Fig. 5b),
and the results indicate functionalized coatings promoted mesenchymal
stem cell to osteoblast and improved osteogenic differentiation and
mineralisation (Fig. 5c) (Chien and Tsai, 2013).
4.1.4. Organic–inorganic composite coating
As a natural composite, bone is mainly composed of organic pro-
teins and inorganic CaP-based materials, where the extracellular or-
ganic matrix (ECM) consists of 90% collagenous proteins and 10% non-
Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 5. (a) (i) Photograph of a mussel attached to commercial PTFE. (ii and iii) Schematic illustrations of the interfacial location of Mefp-5 and a simplified molecular representation of
characteristic amine and catechol groups. (iv) The amino acid sequence of Mefp-5. (v) Dopamine contains both amine and catechol functional groups found in Mefp-5 and was used as a
molecular building block for polymer coatings (Lee et al., 2007). (b) Schematic illustration of dopamine-assisted immobilisation of PEI-g-RGD, hydroxyapatite (HAp) nanoparticles, and
rhBMP-2 on a Ti substrate. (c) 3A6 cells were cultured in the osteogenic medium on different substrates: Ti, dopamine-deposited Ti (Ti-DA), dopamine/PEI-g-RGD-deposited Ti (Ti-DA/
RGD), dopamine/HAp nanoparticle-deposited Ti (Ti-DA/HAp), and dopamine/PEI-g-RGD/HAp nanoparticle-deposited Ti (Ti-DA/RGD/HAp). (i) The cell numbers for 1 or 7 days of
osteogenic culture and (ii) calcium deposition after 14 days of osteogenic culture were determined. ∗, ∗∗, and ∗∗∗ represented p < 0.05, 0.01, and 0.001, respectively. Value =
mean ± standard deviation; n = 4 (Chien and Tsai, 2013).

collagenous proteins and HA, or more specifically carbonate apatite,
makes up more than 50% of our natural bone (LeGeros, 1990).
Therefore, the development of composite coatings inspired by the un-
ique nano-composite structure of bone tissue has become a hot topic for
implant surface functionalization. In addition, there are clinical pro-
blems related to poor adhesion and limited osteoconductivity of current
CaP coatings (de Jonge et al., 2010), together with uncontrollable
loading efficiency or release kinetics of the superficially adsorbed bio-
molecules (Goodman et al., 2013; Siebers et al., 2006). Hence, bio-
molecules–CaP composite coatings can supply superior properties over
the individual components. For example, the ductile properties of col-
lagen can compensate for the poor fracture toughness of CaPs (Fan
et al., 2005), and also promote the CaP coating adhesion, the cell ad-
hesion and thus the fixation of the metallic implant (de Jonge et al.,
2008). The osteoconductivity and bone regeneration at the tissue–im-
plant interface can be improved significantly by immobilising growth
factors such as BMP-2 and TGF-β to the CaP coating (Liu et al., 2005).
CaP or collagen coating can help to create a delayed and sustained
delivery profile or a higher stability of the growth factor and DNA (He
et al., 2012).
As for the coating technologies of the organic–inorganic composite
coatings, electrolytic deposition (ELD), spin coating, and biomimetic
coating methods have been used to generate homogeneous
collagen–CaP composite coatings onto metallic implants (Fan et al.,
2005; Teng et al., 2008), but these coating procedures are time-con-
suming and have poor control over the produced coating thickness (de
Jonge et al., 2010). The electrospray deposition (ESD) is among the
most promising techniques because its low processing temperatures
allow for simultaneous deposition of both biomolecules and CaP (de
Jonge et al., 2009). This method incorporates the growth factors di-
rectly into the inorganic layer, which is conducive to a sustained
biological activity for a considered period of time.
However, the reproduction of the mechanical properties and the
intricately structured organisation of bone have not yet been achieved
for the bioinspired organic–inorganic composite coatings (Roach et al.,
2007). Moreover, the high cost of pure type I collagen and the risk
associated with the primary source of extracted collagen (bovine
spongiform encephalopathy) restrict its applications (Lee et al., 2001).
Therefore, the organic–CaP composite coatings could provide an ad-
vantage over other materials for bone repair application, but further
clinical studies are required to validate its effectiveness.
4.2. Blood compatibility
Blood compatibility is of great importance to the success of many
clinical procedures including blood vessel repair, vascular grafts, stent
and heart valve placements, etc. Chen et al. (2011) and
Dhandayuthapani et al. (2011). Stents are mainly made of metallic
biomaterials due to their excellent mechanical properties regardless of
their poor blood compatibility when compared to biodegradable
polymer stents (Campos et al., 2015; Ma et al., 2014, 2016b; Zhao et al.,
2014). Most metallic biomaterials are electropositive, while blood ele-
ments (platelets and fibrin) tend to be electronegative, thus promote the
formation of thrombi (Ma et al., 2016a, 2016c; Mani et al., 2007).
Blood–material interactions are complex and involve multiple factors
including surface chemical composition, charge, flexibility, wettability
and conditions of blood flow (Chen et al., 2011). In general, the bioinert
(i.e., non-fouling) surfaces can enhance blood contact materials by re-
ducing the intrinsic pathway of blood coagulation (Zhang et al., 2008).
4.2.1. Biomolecule coating
Surface biomolecule coating is the most general approach to

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improve the blood compatibility of metallic stents. Various biologically
active agents and molecules, such as heparin, prostaglandin and some
enzymes, have been investigated as inhibitors of the coagulation pro-
cess, leading to the creation of some clinical devices with anticoagulant
properties (Esmon, 1993; Tepe et al., 2006; Ma et al., 2015b). In ad-
dition, drugs and endothelial cell seeding have also been used in the
surface coatings (Wei et al., 2013). Bioinspired surface functionaliza-
tion with endothelial cell seeding may function in a similar way as the
endothelial surface itself. However, the poor adhesion and slow for-
mation process limit its clinical application, especially in an emergency
situation (Heyligers et al., 2005). Another bioinspired surface functio-
nalization with polydopamine, a mussel adhesive and easily deposited
protein inspired coating materials, can also be applied to metallic
stents. The polydopamine-modified SS316L stents surface shows to re-
duce the adhesion and proliferation of human umbilical artery smooth
muscle cell (HUASMC), while promoted the endothelial cell prolifera-
tion (Yang et al., 2012). The polydopamine can also act as a loading
platform to support the strong anchorage of biologically active agents
and drugs to further improve the blood compatibility (Sobocinski et al.,
2014).
4.2.2. Superhydrophobic surface
Inspired by the lotus-leaf effect, the superhydrophobic surface has
been extensively studied for various engineering and biomedical ap-
plications (Zhang et al., 2008b). It has been demonstrated that super-
hydrophobic surface can strongly affect the protein adsorption, and
thus significantly reduce the adsorption of bovine serum albumin and
completely suppress the platelet adhesion and activation (Patankar,
2004; Sun et al., 2005). For example, superhydrophobic TiO2 nanotubes
have been fabricated by the electrochemical anodization followed by
the perfluorooctyltriethoxysilane (POTS) functionalization on Ti im-
plants with a low adhesion to improve the blood compatibility and
anticoagulation property (Yang et al., 2010). The in vitro blood com-
patibility evaluation demonstrated that superhydrophobic TiO2 nanos-
tructured surfaces possessed good blood compatibility, which effec-
tively resisted the adhesion and activation of platelets, as shown in
Fig. 6. However, the superhydrophobic surfaces rely on trapped air to
repel liquids, which is easy to fail under conditions involving high
temperature, pressure, humidity, and when exposed to low-surface-
tension liquids (Lafuma and Quéré, 2003). Therefore, it remains
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Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
difficult to produce ideal anti-thrombogenic surfaces by super-
hydrophobic coating.
4.2.3. Slippery liquid infused porous surface (SLIPS)
SLIPS was proposed by Wong et al. and fabricated by introducing
liquid lubricants into microstructured substrates with a low surface
energy (Wong et al., 2011), which is inspired by the exceptional re-
pellent ability of the Nepenthes pitcher plant (Fig. 7a), (Chen et al.,
2016; Bohn and Federle, 2004). The surface can repel various simple
and complex liquids (water, hydrocarbons, crude oil and blood),
maintain low contact angle hysteresis, and maintain repellency across a
broad range of temperatures, pressure, surface tension, and other con-
ditions (Wong et al., 2011; Grinthal and Aizenberg, 2013). As for blood
compatibility in biomedical application, Manabe et al. (2015) fabri-
cated biodegradable and biocompatible SLIPS through a low-cost, eco-
friendly, and simple process, which is anti-thrombogenic and en-
vironmentally durable. Although there is no specific study on the me-
tallic stents application of SLIPS, it can be easily integrated into a wide
range of materials and any arbitrary geometries such as pipes (Leslie
et al., 2014). Leslie et al. (2014) applied SLIPS composed of a tethered
perfluorocarbon (TP) layer and a liquid perfluorodecalin (LP), as shown
in Fig. 7b, onto tubing and catheters of indwelling medical devices to
decrease fibrin adhesion and polymerization (Fig. 7c), and thus reduce
morbidity and mortality originating from occlusive thrombosis.
4.3. Biofilm resistance
Biomaterial-associated infection is one of the most frequent com-
plications of medical implants and devices such as orthopaedic im-
plants, cardiovascular stents, vascular catheters, etc. The role of bio-
films in biomedical implant-related infections has been clearly
established (Donlan and Costerton, 2002). Biofilms are composed of
structured micro-organisms adhere firmly to the implant surface and
will produce extracellular polymeric substances, which makes them
resistant to the antibacterial molecules and cells mobilised by the host
(Hook et al., 2012). In order to prevent the infection, there are at least
two strategies for developing a biofilm resistant surface: bactericidal
coatings that kill bacteria by contact or by releasing antimicrobial
agents, and the anti-adhesive surface that decreases or eliminate bac-
terial adhesion (Zhao et al., 2009; Tiller et al., 2001).
Fig. 6. Schematic illustration of platelet
morphology and the corresponding interac-
tions with different surfaces. (a) Plain Ti
substrate; (b) superhydrophilic TiO2 nano-
tubes; and (c) superhydrophobic TiO2 na-
notubes (Yang et al., 2010).
Y. Su et al.
Fig. 7. (a) (i) Optical images of a pitcher of N. alata, showing a conspicuous prey-trapping peristome (left) and a cross-sectional image of the peristome (right) (Chen et al., 2016); (ii)
Peristome surface with first- and second-order radial ridges. Arrows indicate direction toward the inside of the pitcher (Bohn and Federle, 2004); (b) (i) Blood repellency on slippery
tethered-liquid perfluorocarbon (TLP)-coated surfaces; (ii) Photographs of a sliding blood droplet on the slippery surface; (c) (i) Fluorescent micrographs of fibrinogen on acrylic or
polysulfone surfaces with or without TLP coating; (ii) Photographs of polyurethane cannulae, polycarbonate connectors, and PVC tubing with (top) or without (bottom) TLP coating after
8 h of blood flow (Leslie et al., 2014).
4.3.1. Bactericidal biomolecules coating
Various synthetic approaches based on immobilisation or release of
bactericidal substances have been extensively explored to produce
bactericidal coatings (Lichter and Rubner, 2009). It has been reported
antibiotic-loaded D-poly-lactate acid/gentamycin intra-medullary
coated nail was associated with clinically positive results in 6 months
(Fuchs et al., 2011). However, they are not entirely satisfactory for the
biomedical application because of its toxicity, the limited efficiency or
role in the emergence of multi-resisting pathogens. In addition to these
synthetic approaches, some bioinspired methods have been proposed to
prevent bacterial colonisation and biofilm formation. Glinel et al.
(2012) overviewed some bactericidal coatings inspired by these natural
defence strategies and mechanisms in response to an ever-present pa-
thogen pressure. These coatings are designed based on bactericidal and
bioactive compounds, including antimicrobial peptides or bacteriolytic
enzymes which are secreted or produced by numerous living organisms
(Holmberg et al., 2013; Pavlukhina et al., 2012), anti-quorum-sensing
molecules which are able to interrupt cell-to-cell communication within
biofilms and thus inhibit the biofilm formation (Lazar, 2011), and an-
timicrobial essential oils which are natural aromatic oily liquids pro-
duced in various sections (flowers, buds and seeds) of plants such as
rosemary, oregano or thyme (Burt, 2004).
In particular, the surface of orthopaedic and dental implants should
inhibit bacterial colonisation and concomitantly promote osteoblast
functions through its interactions with proteins, bacteria and tissue
cells. Some biomolecules, such as BMP-2 (Shi et al., 2009a, 2009b), and
vascular endothelial growth factor (VEGF) (Hu et al., 2010), can be
immobilised on the implant surface to modulate cellular adhesion of
different cells. For example, compared to that of the pristine Ti alloy,
after being functionalized with VEGF conjugated to carboxymethyl
chitosan, the Ti surface showed a much lower extent of bacterial co-
lonisation (Fig. 8a and b), but enhanced the osteoblast spreading
(Fig. 8c and d) and calcium mineralisation (Fig. 8e and f) (Hu et al.,
2010).
4.3.2. Anti-adhesive surface against bacteria
Many studies about the effects of surface topography, roughness and
wettability on the bacterial adhesion (Anselme et al., 2010; Puckett
et al., 2010). Some natural surfaces with unique topography and wet-
ting property have also have developed the ability to resist or prevent
bacterial adhesion (Barthlott and Neinhuis, 1997; Hasan et al., 2013).
Some of the low-adhesive, superhydrophobic and self-cleaning surfaces
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Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
found in nature such as lotus (Nelumbo nucifera) and taro (Colocasia
esculenta) have been investigated for their potentially anti-biofouling
characteristics (Barthlott and Neinhuis, 1997; Ma et al., 2011). It has
been showed that the nanostructures on taro leaf surface could resist
particle/bacterial adhesion under both wet and non-wet conditions (Ma
et al., 2011). This fact suggests that surfaces with appropriately mod-
ified topography could potentially reduce or prevent bacterial fouling
under completely wetted conditions, which is of great significance for
medical implants (Ye et al., 2014; Fadeeva et al., 2011). It is generally
believed that the anti-adhesion property under non-wet conditions is
attributed to the superhydrophobicity resulting from the hierarchical
surface structure and the trapped air between the nanostructures, while
that under completely wet conditions results from the reduced adhesion
force of the dense nanostructured surface (Hasan et al., 2013; Ma et al.,
2011). Fadeeva et al. (2011) fabricated a superhydrophobic Ti surface
by femtosecond laser ablation, which has the micro- and nanoscale
quasi-periodic self-organised structures inspired by the lotus leaf sur-
face (Ensikat et al., 2011). The bioinspired superhydrophobic Ti surface
can effectively prevent attachment of P. aeruginosa cells, as compared to
the polished Ti surface (Fig. 9a).
The surface of Cicada (Psaltoda claripennis) and dragonfly
(Diplacodes bipunctata) wings has an exclusively antibacterial me-
chanism related to the surface nanostructure (Ivanova et al., 2013;
Ivanova et al., 2012; Pogodin et al., 2013). The attached cells on the
cicada wing surface are mechanically ruptured by the physical inter-
action forces of the surface nanopattern structures (Fig. 9b (iii)). This
bacterial interaction mechanism has been recently proposed (Ivanova
et al., 2012; Pogodin et al., 2013) and used as an inspiration for the
production of TiO2 nanowire arrays on Ti implants to modulate bac-
tericidal activity and osseointegration functionality (Fig. 9b and c) (Diu
et al., 2014; Gao et al., 2013; Bhadra et al., 2015). These studies suggest
that the optimal bioinspired surfaces can increase not only the anti-
bacterial properties but also the adhesion and proliferation of human
cells. In addition, these technologies can be extended to any type of
medical implants or anti-fouling surfaces (Bhadra et al., 2015).
The bioinspired SLIPS, as discussed in Section 4.2, have received
attention as potential antibacterial surfaces owing to the antifouling
property regarding various liquids and environmental stresses (Wang
et al., 2015a). The slippery surface reduced bacterial attachment by
96–97.2% under both static and physiologically realistic flow condi-
tions, and thus the biofilm could be effectively removed under mild
flow conditions (about 1 cm/s) (Epstein et al., 2012). It has also been
Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 8. (a, b) Fluorescence microscopy images of substrates after immersion in a PBS suspension of S. aureus(5 × 107 cells/ml) for 4 h, (c,d) SEM images of osteoblasts 6 h after seeding,
(e,f) Optical microscopy images of Alizarin Red-stained osteoblasts after culturing for 14 days. (a, c,e): Pristine titanium; (b, d,f): Ti functionalized with carboxymethyl chitosan and VEGF
(Hu et al., 2010).

shown that the anti-biofilm performance of this low-cost, passive, and
simple SLIPS is stable in submerged, extreme pH, salinity, and UV en-
vironments.
4.4. Corrosion resistance
Corrosion is degradation of metals due to interaction with their
environment via electrochemical process (Shaw and Kelly, 2006). Me-
tallic biomaterials are subjected to body environment that is very cor-
rosive due to the high concentration of chloride ions and the pH
changes in response to implants. Corrosion can produce harmful metal
ions causing toxicity and allergy, and deteriorating mechanical prop-
erties of the implants (Walczak et al., 1998; Hench and Ethridge, 1975).
Therefore, corrosion resistance has become one of the main selection
criteria of biomaterials. The inert metallic biomaterials generally have
high corrosion resistance due to the presence of protective passive layer
(e.g. the titanium oxide film on Ti and chromium oxide layer for SS).
In order to increase the corrosion resistance of biomaterials in vivo,
a wide variety of approaches have been developed, including surface
coatings, alloying elements, surface mechanical treatment, etc. Shaw
and Kelly (2006). Application of coating is the most suitable route for
metallic implants because the coating could also provide biofunction-
ality in addition to the effective physical protection. Thus, the bioin-
spired biofunctionalization as mentioned in the previous sections could
also be used to effectively protect the metallic implants from corrosion.
Surface superhydrophobization has been one of the most commonly

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Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 9. (a) (i) Optical and SEM images of the lotus leaf (upper side) (Ensikat et al., 2011). (ii) SEM images of femtosecond laser ablated Ti surface inspired by lotus leaf. SEM images of P.
aeruginosa attachment patterns taken at different magnifications on the (iii) structured and (iv) polished Ti surfaces after 18 h incubation (Fadeeva et al., 2011). (b) (i) Optical and SEM
images of cicada wing surface. (ii) SEM images of alkaline hydrothermally treated Ti surface with TiO2 nanowire arrays inspired by Cicada wing surface, the inset is a 30° tilted view
showing sharp nanowire tips; (iii) Three-dimensional representation of the cellular attachment and rupture on the cicada wing surface nanopillars; (iv) SEM images of nanowire-pierced
bacterial cells after one-hour incubations on bioinspired titania surface under dynamic conditions (Pogodin et al., 2013; Diu et al., 2014). (c) (i) Optical and SEM images of the dragonfly
wing surface (Gao et al., 2013). (ii) SEM images of hydrothermal etching Ti surface with TiO2 nanopatterned arrays inspired by dragonfly wing surface; (iii) Confocal scanning laser
microscope (CSLM) images of P.aeruginosa attachment on the (top) untreated and (bottom) nanopatterned Ti surfaces reveal the viable (stained green with SYTO 9) and the non-viable
cells (stained red with Propidium Iodide) (Scale Bar: 10 µm). The antibacterial activity of both substrates was shown in the individual pie charts. (iv) Adhesion and proliferation of human
primary fibroblasts on the (top) untreated and (bottom) nanopatterned Ti surfaces after incubation periods of 10 days (Bhadra et al., 2015).

used bioinspired routes to improve the corrosion resistance with its
unique water-repelling feature. Recently Zhang et al. (2016) reviewed a
variety of typical preparation techniques for superhydrophobic antic-
orrosive surfaces and their anticorrosive performance. Super-
hydrophobic TiO2 coatings have been applied onto biomedical Ti alloys
and SS316L (Jiang et al., 2015; Huang et al., 2015), and some super-
hydrophobic polymer coatings have also been deposited on biomedical
NiTi alloys and Mg alloys (Liu et al., 2008; Li et al., 2014). The common
feature of these superhydrophobic surfaces is a combination of the
hierarchical structures and the low surface free energy. However, the
fabricated superhydrophobic surface has poor resistance to abrasion,
and the Cassie state (i.e., water-repellent state) is metastable, and thus
the wettability easily reaches the Wenzel state (i.e., the wetted state) in
an underwater environment, especially for long-term exposure (Poetes
et al., 2010). Compared with the air fluid trapped in the super-
hydrophobic matrix, the lubricant has a much lower solubility in water
and much higher affinity to the solid matrix, so SLIPS based on a porous
hydrophobic material and high affinitive lubricant can achieve a more
versatile anticorrosive performance (Wang et al., 2015b, 2016).
Biodegradable metals proposed for temporary implants are special
cases for corrosion resistance and should be treated differently for the
surface modification. The preliminary animal tests showed that the
biodegradation rate of Fe alloys is quite low (Peuster et al., 2006;
Hermawan et al., 2010). Hence, in order to achieve a faster degrada-
tion, research has focused on the development of new kinds of Fe alloys
instead of surface modification. As for Zn alloys, the degradation rate is
basically in line with the clinical demand (Bowen et al., 2013; Vojtěch
et al., 2011), so the corrosion rate control is not difficult or even ne-
cessary. On the other hand, the biodegradation property is a double-
edged sword for Mg and its alloys because its high degradation rate not
only prematurely deteriorates its mechanical integrity, but also releases
too much hydrogen gas resulting in subcutaneous gas pocket formation
(Kuhlmann et al., 2013; Noviana et al., 2016). Among the many stra-
tegies to lower the corrosion kinetics of biodegradable Mg and its alloys
(Hornberger et al., 2012; Wang et al., 2012), the CaP-based coating is
one of the latest and most studied techniques (Dorozhkin, 2014;
Shadanbaz and Dias, 2012; Oliveira et al., 2003). Particular attention
should be paid to CaP-based chemical conversion coating because the
electrochemical potential heterogeneity between the α-Mg phase and β
phase in Mg alloys turns to be a positive factor during the coating
process, although it is the main reason for galvanic coupling during the
corrosion process (Li et al., 2006; Su et al., 2016a). It is a simple and
easily controlled method to produce a uniform and well-adhered CaP
coating on Mg alloys and composites (Su et al., 2016a, 2012, 2016b;
Chen et al., 2011; Song et al., 2009), especially for the complex-shaped
components of the orthopaedic implants. It has been shown previously

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Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 10. (a) The surface morphologies of (i) CaP, (ii) HA and (iii) fluorine post-treated CaP (F-CaP) coatings. (b) Hydrogen volume and pH evolution as functions of immersion time in
immersion test in SBF. (c) Mineralisation morphologies and the corresponding appearance photographs (after removing corrosion products) of the uncoated and coated samples immersed
in SBF for 7 days (Su et al., 2015).

that CaP coatings can both increase the corrosion resistance and im-
prove the surface bioactivity of Mg alloys (Su et al., 2012, 2013, 2016c;
Xu et al., 2009). Fig. 10 shows the typical morphologies and the cor-
responding anti-corrosion performances of several different CaP coating
examples (Su et al., 2015).
inflammatory reactions and osteolysis (Jacobs et al., 2001), and thus is
regarded as the primary factor affecting the long-term performance and
life expectancy of joint replacement prostheses. Therefore, surface
functionalization is required to enhance the surface friction and wear
resistance and thus extend the implant longevity (Ghosh and
Abanteriba, 2016).

4.5. Friction and wear resistance

Total hip arthroplasty could significantly improve the life quality of
patients with severe hip osteoarthritis and rheumatoid arthritis.
However, particulate debris generated by adhesive wear, corrosive
wear, and/or abrasive wear may accelerate the deterioration of the
sliding interface (Wang et al., 1998). It may also result in periprosthetic
4.5.1. Surface non-smoothing
Non-smooth surface increases the lubricant film thickness and pro-
vides enlarged portion of the bearing load through generating hydro-
dynamic pressure between the converging surfaces. Thus, it prevents
the solid friction and results in reduced contact area and adhesion
friction (Ghosh and Abanteriba, 2016). For example, the articular

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Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 11. (a) (i) Schematic of a natural knee joint showing the articular cartilage on the condyles of the femur, articulating with the articular cartilage on the tibia. Inset is the magnified
view of the surface of the articular cartilage, obtained with an optical microscope at a 220× magnification (Longmore and Gardner, 1978); (ii) Schematic of the friction experiment, and
contact of the two bearing surfaces, with a magnified view (optical microscope) showing the pattern of spherical indentations (light gray circles) on the CoCr cylinder; (iii) Kinematic
cycle applied to the CoCr cylinder, and friction coefficient f between the CoCr and UHMWPE specimens as a function of time, showing that the bioinspired non-smooth bearing surface
outperforms the smooth bearing surface over most of the kinematic cycle. The data is extracted from a long duration test and the normal load N creates a contact pressure of 11.1 MPa
(Qiu et al., 2014). (b) SEM micrograph of typical shape of dung beetle cuticles: (i) convex shape of head and (ii) stria shape of elytron; (iii) A schematic illustration of biomimetic
specimens; (iv) Wear mass loss as a function of biomimetic unit shape (Zhou et al., 2007).

surface of the skeletal joint is covered by articular cartilage, which clinical practice.
provides long-term smooth joint motion and wear resistance with the
synovial fluid lubrication (Ateshian, 2009). The cartilage surface ex-
4.5.2. Surface coating
hibits a non-smoothing microstructure consisting of shallow spherical
Surface coating techniques have also been used to provide a highly
indentations, as shown in Fig. 11a (i) (Longmore and Gardner, 1978).
wear-resistant surface for artificial joints. Various hard and wear re-
By contrast, prosthetic joints with ultra-smooth bearing surfaces have a
sistant coatings such as metal nitrides, carbides, carbo-nitrides, and
much shorter longevity compared with natural cartilage. Qiu et al.
diamond-like-carbon (DLC) are used in artificial implant applications.
(2014) used a lubrication model to obtain an optimized spherical pat-
Compared to the surface non-smoothing, these coatings can also si-
terned microtexture, which is similar to that of natural cartilage
multaneously enhance the mechanical properties, corrosion resistance
(Fig. 11a (ii)), and experimentally demonstrated that the bioinspired
and wettability of the contact surfaces. The improved wettability can
patterned surface of the Co-Cr femoral component can reduce friction in
increase the lubrication and thus help to decrease the friction and wear
surrogate prosthetic knee bearings, as shown in Fig. 11a (iii).
of implant materials.
Other natural surfaces of animal tissues and plant leaves also pro-
DLC coating is one of a few coatings that have been studied clini-
vided inspiration sources for friction and wear resistance. For
cally and overviewed for biomedical applications in several studies
example, Ren et al. (2001) has been dedicating to the study of the cu-
(Roy and Lee, 2007). Inspired by the natural adaptive behaviour of the
ticle morphologies and principles of soil animals such as dung beetles,
chameleon that changes its colour to match its environment, Voevodin
black ants, and pangolins and found that there were generally five kinds
and Zabinski (2000) developed bioinspired coatings with self-regula-
of non-smooth microstructures on the cuticles, including convex, con-
tion of surface mechanical properties from hard to ductile. The surface
cave, stria, bristle and squama, as called ‘non-smooth construction
chemistry, structure and mechanical behaviour of the bioinspired WC/
units’, which have been found to provide excellent anti-friction prop-
DLC/WS2 nanocomposite coating could reversibly change to maintain
erties against soil. Zhou et al. (2005) and Zhou et al. (2007) applied the
low friction coefficients and long endurance, depending on applied
similar biomimetic principle on the steel surfaces and found the
loads and operational environment in the tribological contact.
bioinspired non-smooth surface could significantly improve the tribo-
Wu et al. (2006) and Jiang et al. (2007) produced cubic boron ni-
logical performance, while non-smooth construction unit shape has
tride (cBN) and Ti nitride (TiN) composite hard coatings with bioin-
significant influences on the abrasive wear resistance, as shown in
spired structures similar to that of taro (Colocasia esculenta) (Fig. 12a
Fig. 11b. It is also reported that bioinspired non-smooth surface similar
(i)-(ii)) and lotus (Nelumbo nucifera) leaf, respectively. The bioinspired
to that of lotus leaf has been designed and exploited to reduce friction
nano-/micro-structure on the surface is effective in entrapping solid
for micro- and nano-devices (Flinn, 2005; Bechert et al., 2000). Greiner
lubricant particles, such as MoS2 and PTFE, and form a soft lubricating
and Schäfer (2015) developed a laser-created surface inspired by the
layer on the composite hard coatings (Fig. 12a (iii)). The bioinspired
skin of snakes and lizards. The bioinspired non-smooth surface sig-
self-lubricating surfaces can effectively reduce friction and improve
nificantly reduced dry sliding friction forces but increased friction by a
wear performance at the frictional contacts (Fig. 12a (iv)-(vi)), and thus
factor of three in lubricated contacts, which is inappropriate for surface
be potentially applied for various tribological implant
treatment of hip implants. This indicates that the tribological perfor-
applications. Singh et al. (2007) replicated the surface topography of a
mance not only depends on the geometrical characteristics but also
real lotus leaf on a poly (methyl methacrylate) (PMMA) coating using a
with the operating conditions. Ghosh et al. (2016) found the non-
capillarity directed soft lithographic technique (Fig. 12b (i)-(ii)). The
smooth surfaces could provide better wear resistance under body or-
bioinspired patterned surface has shown significantly reduced friction
iented fluids than water lubricants. Ibatan et al. (2015) have over-
coefficient and improved wear resistance than that of an unpatterned
viewed the key factors influencing the tribological behaviour of the
surface (Fig. 12b (iii)-(vi)).
non-smooth surface. The surface non-smoothing is a typical bioinspired
In summary, a number of bioinspired surface functionalizations
treatment for engineering applications, with limited studies on its po-
have been proposed for different biomedical purposes, but only a few
tential biomedical application (prosthetic joints). It is currently in the
have been applied for clinical use, such as HA coating and several or-
developing stage but has the great potential to be applied in future
ganic biomolecule coatings. Most of them are still in preclinical studies,

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Y. Su et al. Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105

Fig. 12. (a) SEM images of (i) taro leaf, (ii) bioinspired cBN–TiN coating and (iii) MoS2–PFTE in the valleys formed by TiN papillose protrusions; SEM images showing the wear track after
sliding for (iv) bioinspired cBN–TiN coating; (v) bioinspired MoS2–PTFE on cBN–TiN coating; and (vi) PVD MoS2 coating on WC–Co. Arrow shows sliding direction (Jiang et al., 2007). (b)
SEM images of (i) lotus leaf and (ii) bioinspired patterned PMMA coating. (iii) Friction coefficient and (iv-vi) worn surface of (iv) Si wafer, (v) smooth PMMA coating and (vi) bioinspired
patterned PMMA coating. Bioinspired patterned surface shows superior friction property when compared with smooth PMMA coating and Si wafer (Singh et al., 2007).

and further clinical studies are required to validate its effectiveness. The
success of surface functionalization at the experimental stage, however,
does not guarantee a smooth translation to clinical practice. Not all the
successful techniques at lab scale are found to be clinically practical.
From materials side, the functionalized surfaces should provide non-
cytotoxicity, stability in complex biological media, and specificity for
particular cells/tissues. The structure-activity relationship should be
fully understood to predict their impacts in biological context. From the
cells/tissues side, a detailed knowledge of cellular uptake mechanism of
a functionalized surface is central to improving its clinical efficacy.
Challenges of clinical translation remain due to deficient tissue in-
growth, inadequate control of infections, and the insufficient mechan-
ical strength of certain coatings mimicking the biological functions of
native tissues.
biomaterials, surface functionalization is of particular interest and re-
quirement in the development of high-performance metallic biomater-
ials. Natural functions and strategies provide new sources of inspiration
to create multifunctional surfaces with great potential for biomedical
application. Numerous in vitro studies in this regard have made great
progress but their translation to in vivo studies and similar clinical
outcomes is not yet favourable. More studies on advanced bioinspired
surface functionalizations of metallic biomaterials, together with their
in vivo studies and clinical applications are expected to be developed in
the near future. Learning from nature is a continuous process, and we
are still far away from unlocking the full potential of biomimicry and
bioinspiration.
Acknowledgement

5. Conclusion This work was supported by the China National Nature Science
Foundations (Grant no. U1601203, 51375006, 51705195, and
In order to obtain specific biofunctionalities on the metallic 51675223), China Postdoctoral Science Foundation (Grant no.

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Y. Su et al.
801161082418), and the China Scholarship Council (CSC). YS was
awarded of a mobility grant from the CSC for a one-year training at
Laval University in Canada.
References
Anselme, K., Davidson, P., Popa, A.M., Giazzon, M., Liley, M., Ploux, L., 2010. The in-
teraction of cells and bacteria with surfaces structured at the nanometre scale. Acta
Biomater. 6, 3824.
Arima, Y., Iwata, H., 2007. Effect of wettability and surface functional groups on protein
adsorption and cell adhesion using well-defined mixed self-assembled monolayers.
Biomaterials 28, 3074.
Ateshian, G.A., 2009. The role of interstitial fluid pressurization in articular cartilage
lubrication. J. Biomech. 42, 1163.
Bagherifard, S., Hickey, D.J., de Luca, A.C., Malheiro, V.N., Markaki, A.E., Guagliano, M.,
Webster, T.J., 2015. The influence of nanostructured features on bacterial adhesion
and bone cell functions on severely shot peened 316L stainless steel. Biomaterials 73,
185.
Barrere, F., Van der Valk, C.M., Meijer, G., Dalmeijer, R., De Groot, K., Layrolle, P., 2003.
Osteointegration of biomimetic apatite coating applied onto dense and porous metal
implants in femurs of goats. J. Biomed. Mater. Res. Part B: Appl. Biomater. 67, 655.
Barthlott, W., Neinhuis, C., 1997. Purity of the sacred lotus, or escape from contamination
in biological surfaces. Planta 202, 1.
Bechert, D.W., Bruse, M., Hage, W., Meyer, R., 2000. Fluid mechanics of biological sur-
faces and their technological application. Naturwissenschaften 87, 157.
van den Beucken, J., Walboomers, X.F., Leeuwenburgh, S., Vos, M., Sommerdijk, N.,
Nolte, R., Jansen, J.A., 2007. Multilayered DNA coatings: in vitro bioactivity studies
and effects on osteoblast-like cell behavior. Acta Biomater. 3, 587.
Bhadra, C.M., Vi, K.T., Pham, V.T.H., Al Kobaisi, M., Seniutinas, G., Wang, J.Y.,
Juodkazis, S., Crawford, R.J., Ivanova, E.P., 2015. Antibacterial titanium nano-pat-
terned arrays inspired by dragonfly wings. Sci. Rep. 5.
Bohn, H.F., Federle, W., 2004. Insect aquaplaning: nepenthes pitcher plants capture prey
with the peristome, a fully wettable water-lubricated anisotropic surface. Proc. Natl.
Acad. Sci. USA 101, 14138.
Bowen, P.K., Drelich, J., Goldman, J., 2013. Zinc exhibits ideal physiological corrosion
behavior for bioabsorbable stents. Adv. Mater. 25, 2577.
Burt, S., 2004. Essential oils: their antibacterial properties and potential applications in
foods–a review. Int. J. Food Microbiol 94, 223.
Campos, C.A.M., Zhang, Y.J., Bourantas, C.V., Muramatsu, T., Garcia-Garcia, H.M.,
Lemos, P.A., Iqbal, J., Onuma, Y., Serruys, P.W., 2015. Bioresorbable vascular scaf-
folds in the clinical setting. Interv. Cardiol. 5, 639.
Chen, H., Zhang, P., Zhang, L., Liu, H., Jiang, Y., Zhang, D., Han, Z., Jiang, L., 2016.
Continuous directional water transport on the peristome surface of Nepenthes alata.
Nature 532, 85.
Chen, L., Han, D., Jiang, L., 2011. On improving blood compatibility: from bioinspired to
synthetic design and fabrication of biointerfacial topography at micro/nano scales.
Colloids Surf. B: Biointerfaces 85, 2.
Chen, X.B., Birbilis, N., Abbott, T.B., 2011. A simple route towards a hydroxyapatite–Mg
(OH)2 conversion coating for magnesium. Corros. Sci. 53, 2263.
Chien, C., Tsai, W., 2013. Poly (dopamine)-assisted immobilization of Arg-Gly-Asp pep-
tides, hydroxyapatite, and bone morphogenic protein-2 on titanium to improve the
osteogenesis of bone marrow stem cells. ACS Appl. Mater. Interfaces 5, 6975.
Deligianni, D.D., Katsala, N.D., Koutsoukos, P.G., Missirlis, Y.F., 2000. Effect of surface
roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation,
differentiation and detachment strength. Biomaterials 22, 87.
Deligianni, D.D., Katsala, N., Ladas, S., Sotiropoulou, D., Amedee, J., Missirlis, Y.F., 2001.
Effect of surface roughness of the titanium alloy Ti–6Al–4V on human bone marrow
cell response and on protein adsorption. Biomaterials 22, 1241.
Dhandayuthapani, B., Yoshida, Y., Maekawa, T., Kumar, D.S., 2011. Polymeric scaffolds
in tissue engineering application: a review. Int. J. Polym. Sci. 2011, 290602.
Diu, T., Faruqui, N., Sjostrom, T., Lamarre, B., Jenkinson, H.F., Su, B., Ryadnov, M.G.,
2014. Cicada-inspired cell-instructive nanopatterned arrays. Sci. Rep. 4, 7122.
Donlan, R.M., Costerton, J.W., 2002. Biofilms: survival mechanisms of clinically relevant
microorganisms. Clin. Microbiol Rev. 15, 167.
Dorozhkin, S.V., 2014. Calcium orthophosphate coatings on magnesium and its biode-
gradable alloys. Acta Biomater. 10, 2919.
Douglas, T., Wlodarczyk, M., Pamula, E., Declercq, H.A., Mulder, E., Bucko, M.M.,
Balcaen, L., Vanhaecke, F., Cornelissen, R., Dubruel, P., 2014. Enzymatic miner-
alization of gellan gum hydrogel for bone tissue‐engineering applications and its
enhancement by polydopamine. J. Tissue Eng. Regen. M 8, 906.
Ensikat, H.J., Ditsche-Kuru, P., Neinhuis, C., Barthlott, W., 2011. Superhydrophobicity in
perfection: the outstanding properties of the lotus leaf. Beilstein J. Nanotechnol. 2,
152.
Epstein, A.K., Wong, T., Belisle, R.A., Boggs, E.M., Aizenberg, J., 2012. Liquid-infused
structured surfaces with exceptional anti-biofouling performance. Proc. Natl. Acad.
Sci. USA 109, 13182.
Esmon, C.T., 1993. Cell mediated events that control blood coagulation and vascular
injury. Annu. Rev. Cell Biol. 9, 1.
Fadeeva, E., Truong, V.K., Stiesch, M., Chichkov, B.N., Crawford, R.J., Wang, J., Ivanova,
E.P., 2011. Bacterial retention on superhydrophobic titanium surfaces fabricated by
femtosecond laser ablation. Langmuir 27, 3012.
Fan, Y., Duan, K., Wang, R., 2005. A composite coating by electrolysis-induced collagen
self-assembly and calcium phosphate mineralization. Biomaterials 26, 1623.
Flinn, E.D., 2005. Lotus leaf yields slick idea for MEMS. Aerosp. Am. 43, 24.
103
Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
Fuchs, T., Stange, R., Schmidmaier, G., Raschke, M.J., 2011. The use of gentamicin-coated
nails in the tibia: preliminary results of a prospective study. Arch. Orthop. Traum. Su
131, 1419.
Gao, C., Meng, G., Li, X., Wu, M., Liu, Y., Li, X., Zhao, X., Lee, I., Feng, X., 2013.
Wettability of dragonfly wings: the structure detection and theoretical modeling.
Surf. Interface Anal. 45, 650.
Geetha, M., Singh, A.K., Asokamani, R., Gogia, A.K., 2009. Ti based biomaterials, the
ultimate choice for orthopaedic implants–a review. Prog. Mater. Sci. 54, 397.
Gepreel, M.A., Niinomi, M., 2013. Biocompatibility of Ti-alloys for long-term implanta-
tion. J. Mech. Behav. Biomed. 20, 407.
Ghosh, S., Abanteriba, S., 2016. Status of surface modification techniques for artificial hip
implants. Sci. Technol. Adv. Mat. 17, 715.
Ghosh, S., Choudhury, D., Roy, T., Mamat, A.B., Masjuki, H.H., Pingguan-Murphy, B.,
2016. Tribological investigation of diamond-like carbon coated micro-dimpled sur-
face under bovine serum and osteoarthritis oriented synovial fluid. Sci. Technol. Adv.
Mat. 16, 35002.
Glinel, K., Thebault, P., Humblot, V., Pradier, C.M., Jouenne, T., 2012. Antibacterial
surfaces developed from bio-inspired approaches. Acta Biomater. 8, 1670.
Goodman, S.B., Yao, Z., Keeney, M., Yang, F., 2013. The future of biologic coatings for
orthopaedic implants. Biomaterials 34, 3174.
Greiner, C., Schäfer, M., 2015. Bio-inspired scale-like surface textures and their tribolo-
gical properties. Bioinspir Biomim. 10, 44001.
Grinthal, A., Aizenberg, J., 2013. Mobile interfaces: liquids as a perfect structural material
for multifunctional, antifouling surfaces. Chem. Mater. 26, 698.
Hallab, N.J., Jacobs, J.J., 2013. Orthopedic applications. In: Hoffman, A.S., Schoen, F.J.,
Lemons, J.E. (Eds.), Biomaterials Science: An Introduction to Materials in Medicine,
Third ed. Academic Press, pp. 841.
Han, Z., Niu, S., Shang, C., Liu, Z., Ren, L., 2012. Light trapping structures in wing scales
of butterfly Trogonoptera brookiana. Nanoscale 4, 2879.
Hasan, J., Crawford, R.J., Ivanova, E.P., 2013. Antibacterial surfaces: the quest for a new
generation of biomaterials. Trends Biotechnol. 31, 295.
He, J., Huang, T., Gan, L., Zhou, Z., Jiang, B., Wu, Y., Wu, F., Gu, Z., 2012. Collagen-
infiltrated porous hydroxyapatite coating and its osteogenic properties: In vitro and
in vivo study †. J. Biomed. Mater. Res a 100, 1706.
Hench, L.L., Ethridge, E.C., 1975. Biomaterials—the interfacial problem A2 - BROWN,
J.H.U. In: Dickson, J.F. (Ed.), Advances in Biomedical Engineering. Academic Press,
pp. 35.
Hermawan, H., Purnama, A., Dube, D., Couet, J., Mantovani, D., 2010. Fe–Mn alloys for
metallic biodegradable stents: degradation and cell viability studies. Acta Biomater.
6, 1852.
Heyligers, J.M., Arts, C.H., Verhagen, H.J., de Groot, P.G., Moll, F.L., 2005. Improving
small-diameter vascular grafts: from the application of an endothelial cell lining to
the construction of a tissue-engineered blood vessel. Ann. Vasc. Surg. 19, 448.
Hinderer, S., Layland, S.L., Schenke-Layland, K., 2016. ECM and ECM-like materials —
Biomaterials for applications in regenerative medicine and cancer therapy. Adv. Drug
Deliv. Rev. 97, 260.
Holmberg, K.V., Abdolhosseini, M., Li, Y., Chen, X., Gorr, S., Aparicio, C., 2013. Bio-
inspired stable antimicrobial peptide coatings for dental applications. Acta Biomater.
9, 8224.
Hook, A.L., Chang, C., Yang, J., Luckett, J., Cockayne, A., Atkinson, S., Mei, Y., Bayston,
R., Irvine, D.J., Langer, R., 2012. Combinatorial discovery of polymers resistant to
bacterial attachment. Nat. Biotechnol. 30, 868.
Hornberger, H., Virtanen, S., Boccaccini, A.R., 2012. Biomedical coatings on magnesium
alloys – A review. Acta Biomater. 8, 2442.
Hu, X., Neoh, K., Shi, Z., Kang, E., Poh, C., Wang, W., 2010. An in vitro assessment of
titanium functionalized with polysaccharides conjugated with vascular endothelial
growth factor for enhanced osseointegration and inhibition of bacterial adhesion.
Biomaterials 31, 8854.
Huang, M., Chen, L., Ou, K., Cheng, H., Wang, C., 2015. Rapid osseointegration of tita-
nium implant with innovative nanoporous surface Modification: animal model and
clinical trial. Implant Dent. 24, 441.
Huang, Q., Yang, Y., Hu, R., Lin, C., Sun, L., Vogler, E.A., 2015. Reduced platelet adhesion
and improved corrosion resistance of superhydrophobic TiO2-nanotube-coated 316L
stainless steel. Colloids Surf. B: Biointerfaces 125, 134.
Ibatan, T., Uddin, M.S., Chowdhury, M.A.K., 2015. Recent development on surface tex-
turing in enhancing tribological performance of bearing sliders. Surf. Coat. Technol.
272, 102.
Ivanova, E.P., Hasan, J., Webb, H.K., Vi, K.T., Watson, G.S., Watson, J.A., Baulin, V.A.,
Pogodin, S., Wang, J.Y., Tobin, M.J., Loebbe, C., Crawford, R.J., 2012. Natural
bactericidal surfaces: mechanical rupture of pseudomonas aeruginosa cells by cicada
wings. SMALL 8, 2489.
Ivanova, E.P., Hasan, J., Webb, H.K., Gervinskas, G., Juodkazis, S., Vi, K.T., Wu, A.H.F.,
Lamb, R.N., Baulin, V.A., Watson, G.S., Watson, J.A., Mainwaring, D.E., Crawford,
R.J., 2013. Bactericidal activity of black silicon. Nat. Commun. 4, 2838.
Izquierdo-Barba, I., García-Martín, J.M., Álvarez, R., Palmero, A., Esteban, J., Pérez-
Jorge, C., Arcos, D., Vallet-Regí, M., 2015. Nanocolumnar coatings with selective
behavior towards osteoblast and Staphylococcus aureus proliferation. Acta Biomater.
15, 20.
Jacobs, J.J., Roebuck, K.A., Archibeck, M., Hallab, N.J., Glant, T.T., 2001. Osteolysis:
basic science. Clin. Orthop. Relat. R. 393, 71.
Jiang, J.Y., Xu, J.L., Liu, Z.H., Deng, L., Sun, B., Liu, S.D., Wang, L., Liu, H.Y., 2015.
Preparation, corrosion resistance and hemocompatibility of the superhydrophobic
TiO2 coatings on biomedical Ti-6Al-4V alloys. Appl. Surf. Sci. 347, 591.
Jiang, W., Malshe, A.P., Wu, J.H., 2007. Bio-mimetic surface structuring of coating for
tribological applications. Surf. Coat. Technol. 201, 7889.
de Jonge, L.T., Leeuwenburgh, S.C.G., Wolke, J.G.C., Jansen, J.A., 2008.
Y. Su et al.
Organic–inorganic surface modifications for titanium implant surfaces. Pharm. Res.
25, 2357.
de Jonge, L.T., Jj, V.D.B., Leeuwenburgh, S.C., Hamers, A.A., Wolke, J.G., Jansen, J.A.,
2009. In vitro responses to electrosprayed alkaline phosphatase/calcium phosphate
composite coatings. Acta Biomater. 5, 2773.
de Jonge, L.T., Leeuwenburgh, S.C.G., van den Beucken, J.J.J.P., Te Riet, J., Daamen,
W.F., Wolke, J.G.C., Scharnweber, D., Jansen, J.A., 2010. The osteogenic effect of
electrosprayed nanoscale collagen/calcium phosphate coatings on titanium.
Biomaterials 31, 2461.
Khang, D., Lu, J., Yao, C., Haberstroh, K.M., Webster, T.J., 2008. The role of nanometer
and sub-micron surface features on vascular and bone cell adhesion on titanium.
Biomaterials 29, 970.
Koch, K., Bhushan, B., Barthlott, W., 2009. Multifunctional surface structures of plants: an
inspiration for biomimetics. Prog. Mater. Sci. 54, 137.
Kolle, M., Salgard-Cunha, P.M., Scherer, M.R., Huang, F., Vukusic, P., Mahajan, S.,
Baumberg, J.J., Steiner, U., 2010. Mimicking the colourful wing scale structure of the
Papilio blumei butterfly. Nat. Nanotechnol. 5, 511.
Kuhlmann, J., Bartsch, I., Willbold, E., Schuchardt, S., Holz, O., Hort, N., Höche, D.,
Heineman, W.R., Witte, F., 2013. Fast escape of hydrogen from gas cavities around
corroding magnesium implants. Acta Biomater. 9, 8714.
Lafuma, A., Quéré, D., 2003. Superhydrophobic states. Nat. Mater. 2, 457.
Lai, Y., Pan, F., Xu, C., Fuchs, H., Chi, L., 2013. In situ surface‐modification‐induced
superhydrophobic patterns with reversible wettability and adhesion. Adv. Mater. 25,
1682.
Launey, M.E., Buehler, M.J., Ritchie, R.O., 2010. On the mechanistic origins of toughness
in bone. Annu. Rev. Mater. Res. 40, 25.
Lazar, V., 2011. Quorum sensing in biofilms–how to destroy the bacterial citadels or their
cohesion/power? Anaerobe 17, 280.
Lee, C.H., Singla, A., Lee, Y., 2001. Biomedical applications of collagen. Int. J. Pharm.
221, 1.
Lee, H., Dellatore, S.M., Miller, W.M., Messersmith, P.B., 2007. Mussel-inspired surface
chemistry for multifunctional coatings. Science 318, 426.
Lee, J., Han, H., Han, K., Park, J., Jeon, H., Ok, M., Seok, H., Ahn, J., Lee, K.E., Lee, D.,
Yang, S., Cho, S., Cha, P., Kwon, H., Nam, T., Han, J.H.L., Rho, H., Lee, K., Kim, Y.,
Mantovani, D., 2016. Long-term clinical study and multiscale analysis of in vivo
biodegradation mechanism of Mg alloy. Proc. Natl. Acad. Sci. 113, 716.
LeGeros, R.Z., 1990. Calcium phosphates in oral biology and medicine. Monogr. Oral. Sci.
15, 1.
Leslie, D.C., Waterhouse, A., Berthet, J.B., Valentin, T.M., Watters, A.L., Jain, A., Kim, P.,
Hatton, B.D., Nedder, A., Donovan, K., Super, E.H., Howell, C., Johnson, C.P., Vu,
T.L., Bolgen, D.E., Rifai, S., Hansen, A.R., Aizenberg, M., Super, M., Aizenberg, J.,
Ingber, D.E., 2014. A bioinspired omniphobic surface coating on medical devices
prevents thrombosis and biofouling. Nat. Biotechnol. 32, 1134.
Li, G.Y., Lian, J.S., Niu, L.Y., Jiang, Z.H., Jiang, Q., 2006. Growth of zinc phosphate
coatings on AZ91D magnesium alloy. Surf. Coat. Technol. 201, 1814.
Li, P., Li, L., Wang, W., Jin, W., Liu, X., Yeung, K.W.K., Chu, P.K., 2014. Enhanced cor-
rosion resistance and hemocompatibility of biomedical NiTi alloy by atmospheric-
pressure plasma polymerized fluorine-rich coating. Appl. Surf. Sci. 297, 109.
Lichter, J.A., Rubner, M.F., 2009. Polyelectrolyte multilayers with intrinsic antimicrobial
functionality: the importance of mobile polycations. Langmuir ACS J. Surf. Colloids
25, 7686.
Lin, J., Ozan, S., Li, Y., Ping, D., Tong, X., Li, G., Wen, C., 2016. Novel Ti-Ta-Hf-Zr alloys
with promising mechanical properties for prospective stent applications. Sci. Rep. 6,
37901.
Liu, K., Zhang, M., Zhai, J., Wang, J., Jiang, L., 2008. Bioinspired construction of Mg–Li
alloys surfaces with stable superhydrophobicity and improved corrosion resistance.
Appl. Phys. Lett. 92, 183103.
Liu, K., Yao, X., Jiang, L., 2010. Recent developments in bio-inspired special wettability.
Chem. Soc. Rev. 39, 3240.
Liu, Y., De, G.K., Hunziker, E.B., 2005. BMP-2 liberated from biomimetic implant coatings
induces and sustains direct ossification in an ectopic rat model. Bone 36, 745.
Liu, X., Chu, P., Ding, C., 2004. Surface modification of titanium, titanium alloys, and
related materials for biomedical applications. Mater. Sci. Eng.: R: Rep. 47, 49.
Longmore, R.B., Gardner, D.L., 1978. The surface structure of ageing human articular
cartilage: a study by reflected light interference microscopy (RLIM). J. Anat. 126,
353.
Lorenzetti, M., Dakischew, O., Trinkaus, K., Susanne Lips, K., Schnettler, R., Kobe, S.,
Novak, S., 2015. Enhanced osteogenesis on titanium implants by UVB photo-
functionalization of hydrothermally grown TiO2 coatings. J. Biomater. Appl. 30, 71.
Lynge, M.E., Schattling, P., Städler, B., 2015. Recent developments in poly (dopamine)-
based coatings for biomedical applications. Nanomedicine 10, 2725.
Ma, J., Sun, Y., Gleichauf, K., Lou, J., Li, Q., 2011. Nanostructure on taro leaves resists
fouling by colloids and bacteria under submerged conditions. Langmuir 27, 10035.
Ma, J., Thompson, M., Zhao, N., Zhu, D., 2014. Similarities and differences in coatings for
magnesium-based stents and orthopaedic implants. J. Orthop. Transl. 2, 118.
Ma, J., Zhao, N., Zhu, D., 2015a. Endothelial cellular responses to biodegradable metal
zinc. ACS Biomater. Sci. Eng. 1, 1174.
Ma, J., Zhao, N., Zhu, D., 2015b. Sirolimus-eluting dextran and polyglutamic acid hybrid
coatings on AZ31 for stent applications. J. Biomater. Appl. 30, 579.
Ma, J., Zhao, N., Zhu, D., 2016a. Biphasic responses of human vascular smooth muscle
cells to magnesium ion. J. Biomed. Mater. Res. 104, 347.
Ma, J., Zhao, N., Betts, L., Zhu, D., 2016b. Bio-adaption between magnesium alloy stent
and the blood vessel: a review. J. Mater. Sci. Technol. 32, 815.
Ma, J., Zhao, N., Zhu, D., 2016c. Bioabsorbable zinc ion induced biphasic cellular re-
sponses in vascular smooth muscle cells. Sci. Rep. 6, 26661.
Manabe, K., Kyung, K., Shiratori, S., 2015. Biocompatible slippery fluid-infused films
104
Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
composed of chitosan and alginate via layer-by-layer self-assembly and their an-
tithrombogenicity. ACS Appl. Mater. Inter 7, 4763.
Mani, G., Feldman, M.D., Patel, D., Agrawal, C.M., 2007. Coronary stents: a materials
perspective. Biomaterials 28, 1689.
Narushima, T., Mineta, S., Kurihara, Y., Ueda, K., 2013. Precipitates in biomedical Co-Cr
alloys. JOM-US 65, 489.
Nel, A.E., Mädler, L., Velegol, D., Xia, T., Hoek, E.M., Somasundaran, P., Klaessig, F.,
Castranova, V., Thompson, M., 2009. Understanding biophysicochemical interactions
at the nano–bio interface. Nat. Mater. 8, 543.
Niinomi, M., Nakai, M., Hieda, J., 2012. Development of new metallic alloys for bio-
medical applications. Acta Biomater. 8, 3888.
Noviana, D., Paramitha, D., Ulum, M.F., Hermawan, H., 2016. The effect of hydrogen gas
evolution of magnesium implant on the postimplantation mortality of rats. J. Orthop.
Transl. 5, 9.
Oliveira, A.L., Mano, J.F., Reis, R.L., 2003. Nature-inspired calcium phosphate coatings:
present status and novel advances in the science of mimicry. Curr. Opin. Solid State
Mater. Sci. 7, 309.
Paital, S.R., Dahotre, N.B., 2009. Calcium phosphate coatings for bio-implant applica-
tions: materials, performance factors, and methodologies. Mater. Sci. Eng.: R: Rep.
66, 1.
Patankar, N.A., 2004. Mimicking the lotus effect: influence of double roughness structures
and slender pillars. Langmuir 20, 8209.
Pavlukhina, S.V., Kaplan, J.B., Li, X., Wei, C., Yu, X., Madhyastha, S., Yakandawala, N.,
Mentbayeva, A., Khan, B., Sukhishvili, S.A., 2012. Noneluting enzymatic antibiofilm
coatings. ACS Appl. Mater. Interfaces 4, 4708.
Peuster, M., Hesse, C., Schloo, T., Fink, C., Beerbaum, P., von Schnakenburg, C., 2006.
Long-term biocompatibility of a corrodible peripheral iron stent in the porcine des-
cending aorta. Biomaterials 27, 4955.
Planell, J.A., Navarro, M., Altankov, G., Aparicio, C., Engel, E., Gil, J., Ginebra, M.P.,
Lacroix, D., 2010. Materials surface effects on biological interactions. Adv. Regener.
Med. Role Nanotechnol. Eng. Princ. 233.
Poetes, R., Holtzmann, K., Franze, K., Steiner, U., 2010. Metastable underwater super-
hydrophobicity. Phys. Rev. Lett. 105, 166104.
Pogodin, S., Hasan, J., Baulin, V.A., Webb, H.K., Vi, K.T., The, H.P.N., Boshkovikj, V.,
Fluke, C.J., Watson, G.S., Watson, J.A., Crawford, R.J., Ivanova, E.P., 2013.
Biophysical model of bacterial cell interactions with nanopatterned cicada wing
surfaces. Biophys. J. 104, 835.
Puckett, S.D., Taylor, E., Raimondo, T., Webster, T.J., 2010. The relationship between the
nanostructure of titanium surfaces and bacterial attachment. Biomaterials 31, 706.
Qiu, M., Chyr, A., Sanders, A.P., Raeymaekers, B., 2014. Designing prosthetic knee joints
with bio-inspired bearing surfaces. Tribol. Int. 77, 106.
Ratner, B.D., Hoffman, A.S., Schoen, F.J., Lemons, J.E., 2004. Biomaterials Science: An
Introduction to Materials in Medicine. Academic Press, New York.
Ren, L., Tong, J., Li, J., Chen, B., 2001. SW—soil and water: soil adhesion and biomi-
metics of soil-engaging components: a review. J. Agric. Eng. Res. 79, 239.
Ritchie, R.O., 2011. The conflicts between strength and toughness. Nat. Mater. 10, 817.
Roach, P., Eglin, D., Rohde, K., Perry, C.C., 2007. Modern biomaterials: a review—bulk
properties and implications of surface modifications. J. Mater. Sci.: Mater. Med. 18,
1263.
Ronga, M., Fagetti, A., Canton, G., Paiusco, E., Surace, M.F., Cherubino, P., 2013. Clinical
applications of growth factors in bone injuries: experience with BMPs. Injury 44, S34.
Rosales-Leal, J.I., Rodríguez-Valverde, M.A., Mazzaglia, G., Ramon-Torregrosa, P.J., Diaz-
Rodriguez, L., Garcia-Martinez, O., Vallecillo-Capilla, M., Ruiz, C., Cabrerizo-Vilchez,
M.A., 2010. Effect of roughness, wettability and morphology of engineered titanium
surfaces on osteoblast-like cell adhesion. Colloids Surf. A: Physicochem. Eng. Asp.
365, 222.
Roy, R.K., Lee, K.R., 2007. Biomedical applications of diamond‐like carbon coatings: a
review. J. Biomed. Mater. Res. Part B: Appl. Biomater. 83, 72.
Shadanbaz, S., Dias, G.J., 2012. Calcium phosphate coatings on magnesium alloys for
biomedical applications: a review. Acta Biomater. 8, 20.
Shaw, B.A., Kelly, R.G., 2006. What is corrosion? Interface-electrochemical. Society
15, 24.
Shen, X., Ma, P., Hu, Y., Xu, G., Zhou, J., Cai, K., 2015. Mesenchymal stem cell growth
behavior on micro/nano hierarchical surfaces of titanium substrates. Colloids Surf. B:
Biointerfaces 127, 221.
Shi, Z., Neoh, K.G., Kang, E.T., Poh, C.K., Wang, W., 2009. Titanium with surface-grafted
dextran and immobilized bone morphogenetic protein-2 for inhibition of bacterial
adhesion and enhancement of osteoblast functions. Tissue Eng. Part A 15, 417.
Shi, Z., Neoh, K.G., Kang, E.T., Poh, C.K., Wang, W., 2009. Surface functionalization of
titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-
2 for enhanced osseointegration. Biomacromolecules 10, 1603.
Shin, S., Seo, J., Han, H., Kang, S., Kim, H., Lee, T., 2016. Bio-inspired extreme wetting
surfaces for biomedical applications. Materials 9, 116.
Shirtcliffe, N.J., McHale, G., Newton, M.I., Perry, C.C., Pyatt, F.B., 2006. Plastron prop-
erties of a superhydrophobic surface. Appl. Phys. Lett. 89, 104106.
Siebers, M.C., Walboomers, X.F., Leewenburgh, S.C., Wolke, J.C., Boerman, O.C., Jansen,
J.A., 2006. Transforming growth factor-beta1 release from a porous electrostatic
spray deposition-derived calcium phosphate coating. Tissue Eng. 12, 2449.
Silva-Bermudez, P., Rodil, S.E., 2013. An overview of protein adsorption on metal oxide
coatings for biomedical implants. Surf. Coat. Technol. 233, 147.
Singh, R.A., Yoon, E., Kim, H.J., Kong, H., Park, S., Jeong, H.E., Suh, K.Y., 2007.
Enhanced tribological properties of lotus leaf-like surfaces fabricated by capillary
force lithography. Surf. Eng. 23, 161.
Sobocinski, J., Laure, W., Taha, M., Courcot, E., Feng, C., Simon, N., Addad, A., Martel, B.,
Haulon, S., Woisel, P., 2014. Mussel inspired coating of a biocompatible cyclodextrin
based polymer onto CoCr vascular stents. ACS Appl. Mater. Interfaces 6, 3575.
Y. Su et al.
Song, W., Mano, J.F., 2013. Interactions between cells or proteins and surfaces exhibiting
extreme wettabilities. Soft Matter 9, 2985.
Song, Y., Shan, D., Chen, R., Zhang, F., Han, E., 2009. Formation mechanism of phosphate
conversion film on Mg–8.8Li alloy. Corros. Sci. 51, 62.
Staiger, M.P., Pietak, A.M., Huadmai, J., Dias, G., 2006. Magnesium and its alloys as
orthopedic biomaterials: a review. Biomaterials 27, 1728.
Su, Y., Li, G., Lian, J., 2012. A chemical conversion hydroxyapatite coating on AZ60
magnesium alloy and its electrochemical corrosion behaviour. Int. J. Electrochem. Sc.
7, 11497.
Su, Y., Niu, L., Lu, Y., Lian, J., Li, G., 2013. Preparation and corrosion behavior of calcium
phosphate and hydroxyapatite conversion coatings on AM60 magnesium alloy. J.
Electrochem. Soc. 160, C536.
Su, Y., Lu, Y., Su, Y., Hu, J., Lian, J., Li, G., 2015. Enhancing the corrosion resistance and
surface bioactivity of a calcium-phosphate coating on a biodegradable AZ60 mag-
nesium alloy via a simple fluorine post-treatment method. RSC Adv. 5, 56001.
Su, Y., Li, D., Su, Y., Lu, C., Niu, L., Lian, J., Li, G., 2016a. Improvement of the biode-
gradation property and biomineralization ability of magnesium–hydroxyapatite
composites with dicalcium phosphate Dihydrate and hydroxyapatite coatings. ACS
Biomater. Sci. Eng. 2, 818.
Su, Y., Su, Y., Lu, Y., Lian, J., Li, G., 2016b. Composite microstructure and formation
mechanism of calcium phosphate conversion coating on magnesium alloy. J.
Electrochem Soc. 163, G138.
Su, Y., Guo, Y., Huang, Z., Zhang, Z., Li, G., Lian, J., Ren, L., 2016c. Preparation and
corrosion behaviors of calcium phosphate conversion coating on magnesium alloy.
Surf. Coat. Technol. 307, 99.
Sun, T., Tan, H., Han, D., Fu, Q., Jiang, L., 2005. No platelet can adhere—largely im-
proved blood compatibility on nanostructured superhydrophobic surfaces. Small 1,
959.
Surmenev, R.A., Surmeneva, M.A., Ivanova, A.A., 2014. Significance of calcium phos-
phate coatings for the enhancement of new bone osteogenesis – a review. Acta
Biomater. 10, 557.
Talha, M., Behera, C.K., Sinha, O.P., 2013. A review on nickel-free nitrogen containing
austenitic stainless steels for biomedical applications. Mater. Sci. Eng.: C 33, 3563.
Teng, S.H., Lee, E.J., Park, C.S., Choi, W.Y., Shin, D.S., Kim, H.E., 2008. Bioactive na-
nocomposite coatings of collagen/hydroxyapatite on titanium substrates. J. Mater.
Sci.: Mater. Med. 19, 2453.
Tepe, G., Schmehl, J., Wendel, H.P., Schaffner, S., Heller, S., Gianotti, M., Claussen, C.D.,
Duda, S.H., 2006. Reduced thrombogenicity of nitinol stents—in vitro evaluation of
different surface modifications and coatings. Biomaterials 27, 643.
Thevenot, P., Hu, W., Tang, L., 2008. Surface chemistry influences implant biocompat-
ibility. Curr. Top. Med Chem. 8, 270.
Tiller, J.C., Liao, C., Lewis, K., Klibanov, A.M., 2001. Designing surfaces that kill bacteria
on contact. Proc. Natl. Acad. Sci. 98, 5981.
Vaquette, C., Ivanovski, S., Hamlet, S.M., Hutmacher, D.W., 2013. Effect of culture
conditions and calcium phosphate coating on ectopic bone formation. Biomaterials
34, 5538.
Voevodin, A.A., Zabinski, J.S., 2000. Supertough wear-resistant coatings with 'chameleon'
surface adaptation. Thin Solid Films 370, 223.
Vojtěch, D., Kubásek, J., Šerák, J., Novák, P., 2011. Mechanical and corrosion properties
of newly developed biodegradable Zn-based alloys for bone fixation. Acta Biomater.
7, 3515.
Walczak, J., Shahgaldi, F., Heatley, F., 1998. In vivo corrosion of 316L stainless-steel hip
implants: morphology and elemental compositions of corrosion products.
Biomaterials 19, 229.
Wang, A., Essner, A., Polineni, V.K., Stark, C., Dumbleton, J.H., 1998. Lubrication and
wear of ultra-high molecular weight polyethylene in total joint replacements. Tribol.
Int. 31, 17.
Wang, F., Shi, L., He, W., Han, D., Yan, Y., Niu, Z., Shi, S., 2013. Bioinspired micro/nano
fabrication on dental implant–bone interface. Appl. Surf. Sci. 265, 480.
Wang, G., Li, J., Lv, K., Zhang, W., Ding, X., Yang, G., Liu, X., Jiang, X., 2016. Surface
thermal oxidation on titanium implants to enhance osteogenic activity and in vivo
osseointegration. Sci. Rep. 6, 31769.
Wang, J., Tang, J., Zhang, P., Li, Y., Wang, J., Lai, Y., Qin, L., 2012. Surface modification
of magnesium alloys developed for bioabsorbable orthopedic implants: a general
review. J. Biomed. Mater. Res. Part B: Appl. Biomater. 100B, 1691.
Wang, P., Zhang, D., Lu, Z., 2015a. Slippery liquid-infused porous surface bio-inspired by
pitcher plant for marine anti-biofouling application. Colloid Surf. B 136, 240.
Wang, P., Lu, Z., Zhang, D., 2015b. Slippery liquid-infused porous surfaces fabricated on
aluminum as a barrier to corrosion induced by sulfate reducing bacteria. Corros. Sci.
93, 159.
Wang, P., Zhang, D., Lu, Z., Sun, S., 2016. Fabrication of slippery lubricant-infused porous
surface for inhibition of microbially influenced. Corros. ACS Appl. Mater. Interfaces
8, 1120.
105
Journal of the Mechanical Behavior of Biomedical Materials 77 (2018) 90–105
Wang, S., Liu, K., Yao, X., Jiang, L., 2015. Bioinspired surfaces with superwettability: new
insight on theory, design, and applications. Chem. Rev. 115, 8230.
Wang, Y., Robertson, J.L., Spillman Jr, W.B., Claus, R.O., 2004. Effects of the chemical
structure and the surface properties of polymeric biomaterials on their biocompat-
ibility. Pharm. Res-Dordr. 21, 1362.
Webb, H.K., Hasan, J., Truong, V.K., Crawford, R.J., Ivanova, E.P., 2011. Nature inspired
structured surfaces for biomedical applications. Curr. Med. Chem. 18, 3367.
Wei, J., Yoshinari, M., Takemoto, S., Hattori, M., Kawada, E., Liu, B., Oda, Y., 2007.
Adhesion of mouse fibroblasts on hexamethyidisiloxane surfaces with wide range of
wettability. J. Biomed. Mater. Res B 81B, 66.
Wei, Y., Ji, Y., Xiao, L., Lin, Q., Xu, J., Ren, K., Ji, J., 2013. Surface engineering of car-
diovascular stent with endothelial cell selectivity for in vivo re-endothelialisation.
Biomaterials 34, 2588.
Wong, T., Kang, S.H., Tang, S.K.Y., Smythe, E.J., Hatton, B.D., Grinthal, A., Aizenberg, J.,
2011. Bioinspired self-repairing slippery surfaces with pressure-stable omniphobicity.
Nature 477, 443.
Wu, J.H., Phillips, B.S., Jiang, W., Sanders, J.H., Zabinski, J.S., Malshe, A.P., 2006. Bio-
inspired surface engineering and tribology of MoS2 overcoated cBN–TiN composite
coating. Wear 261, 592.
Xu, L., Pan, F., Yu, G., Yang, L., Zhang, E., Yang, K., 2009. In vitro and in vivo evaluation
of the surface bioactivity of a calcium phosphate coated magnesium alloy.
Biomaterials 30, 1512.
Yan, Y., Neville, A., Dowson, D., 2007. Tribo-corrosion properties of cobalt-based medical
implant alloys in simulated biological environments. Wear 263, 1105.
Yang, Y., Kim, K.H., Ong, J.L., 2005. A review on calcium phosphate coatings produced
using a sputtering process – an alternative to plasma spraying. Biomaterials 26, 327.
Yang, Y., Lai, Y., Zhang, Q., Wu, K., Zhang, L., Lin, C., Tang, P., 2010. A novel electro-
chemical strategy for improving blood compatibility of titanium-based biomaterials.
Colloids Surf. B: Biointerfaces 79, 309.
Yang, Z., Tu, Q., Zhu, Y., Luo, R., Li, X., Xie, Y., Maitz, M.F., Wang, J., Huang, N., 2012.
Mussel-inspired coating of polydopamine directs endothelial and smooth muscle cell
fate for re-endothelialization of vascular devices. Adv. Healthc. Mater. 1, 548.
Yao, X., Song, Y., Jiang, L., 2011. Applications of bio-inspired special wettable surfaces.
Adv. Mater. 23, 719.
Ye, W., Shi, Q., Hou, J., Jin, J., Fan, Q., Wong, S., Xu, X., Yin, J., 2014. Superhydrophobic
coating of elastomer on different substrates using a liquid template to construct a
biocompatible and antibacterial surface. J. Mater. Chem. B 2, 7186.
Zhang, D., Wang, L., Qian, H., Li, X., 2016. Superhydrophobic surfaces for corrosion
protection: a review of recent progresses and future directions. J. Coat. Technol. Res.
13, 11.
Zhang, X., Shi, F., Niu, J., Jiang, Y., Wang, Z., 2008a. Superhydrophobic surfaces: from
structural control to functional application. J. Mater. Chem. 18, 621.
Zhang, X., Shi, F., Niu, J., Jiang, Y., Wang, Z., 2008b. Superhydrophobic surfaces: from
structural control to functional application. J. Mater. Chem. 18, 621.
Zhang, Z., Zhang, M., Chen, S., Horbett, T.A., Ratner, B.D., Jiang, S., 2008. Blood com-
patibility of surfaces with superlow protein adsorption. Biomaterials 29, 4285.
Zhao, G., Raines, A.L., Wieland, M., Schwartz, Z., Boyan, B.D., 2007. Requirement for
both micron- and submicron scale structure for synergistic responses of osteoblasts to
substrate surface energy and topography. Biomaterials 28, 2821.
Zhao, L., Chu, P.K., Zhang, Y., Wu, Z., 2009. Antibacterial coatings on titanium implants.
J. Biomed. Mater. Res. Part B: Appl. Biomater. 91, 470.
Zhao, N., Zhu, D., 2014. Collagen self-assembly on orthopedic magnesium biomaterials
surface and subsequent bone cell attachment. PloS One 9, e110420.
Zhao, N., Watson, N., Xu, Z., Chen, Y., Waterman, J., Sankar, J., Zhu, D., 2014. In vitro
biocompatibility and endothelialization of novel magnesium-rare earth alloys for
improved stent applications. PloS One 9, e98674.
Zheng, Y.F., Gu, X.N., Witte, F., 2014. Biodegradable metals. Mater. Sci. Eng.: R: Rep.
77, 1.
Zhou, H., Chen, L., Wang, W., Ren, L.Q., Shan, H.Y., Zhang, Z.H., 2005. Abrasive particle
wear behavior of 3Cr2W8V steel processed to bionic non-smooth surface by laser.
Mater. Sci. Eng.: A 412, 323.
Zhou, H., Sun, N., Shan, H., Ma, D., Tong, X., Ren, L., 2007. Bio-inspired wearable
characteristic surface: wear behavior of cast iron with biomimetic units processed by
laser. Appl. Surf. Sci. 253, 9513.
Zhu, D., Su, Y., Young, M., Ma, J., Zheng, Y., Tang, L., 2017. Biological responses and
mechanisms of human bone marrow mesenchymal stem cells to Zn and Mg bioma-
terials. ACS Appl. Mater. Interfaces.
Zinger, O., Zhao, G., Schwartz, Z., Simpson, J., Wieland, M., Landolt, D., Boyan, B.,
2005a. Differential regulation of osteoblasts by substrate microstructural features.
Biomaterials 26, 1837.
Zinger, O., Zhao, G., Schwartz, Z., Simpson, J., Wieland, M., Landolt, D., Boyan, B.,
2005b. Differential regulation of osteoblasts by substrate microstructural features.
Biomaterials 26, 1837.