Acta Biomaterialia 89 (2019) 14–32

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Acta Biomaterialia
journal homepage: www.elsevier.com/locate/actabiomat

Review article

Ion-substituted calcium phosphate coatings by physical vapor

deposition magnetron sputtering for biomedical applications: A review
Muhammad Qadir, Yuncang Li, Cuie Wen ⇑
School of Engineering, RMIT University, Bundoora, Victoria 3083, Australia

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

Article history: Coatings based on ion-substituted calcium phosphate (Ca-P) have attracted great attention in the scien-
Received 15 October 2018 tific community over the past decade for the development of biomedical applications. Among such Ca-P
Received in revised form 2 March 2019 based structures, hydroxyapatite (HA) has shown significant influence on cell behaviors including cell
Accepted 5 March 2019
proliferation, adhesion, and differentiation. These cell behaviors determine the osseointegration between
Available online 6 March 2019
the implant and host bone and the biocompatibility of implants. This review presents a critical analysis
on the physical vapor deposition magnetron sputtering (PVDMS) technique that has been used for ion-
Keywords:
substituted Ca-P based coatings on implants materials. The effect of PVDMS processing parameters such
Biocompatible coating
PVD magnetron sputtering
as discharge power, bias voltage, deposition time, substrate temperature, and post-heat treatment on the
Calcium phosphate surface properties of ion-substituted Ca-P coatings is elucidated. Moreover, the advantages, short com-
Hydroxyapatite coating ings and future research directions of Ca-P coatings by PVDMS have been comprehensively analyzed. It
is revealed that the topography and surface chemistry of amorphous HA coatings influence the cell
behavior, and ion-substituted HA coatings significantly increase cell attachment but may result in a
cytotoxic effect that reduces the growth of the cells attached to the coating surface areas. Meanwhile,
low-crystalline HA coatings exhibit lower rates of osteogenic cell proliferation as compared to highly
crystalline HA coatings developed on Ti based surfaces. PVDMS allows a close reproduction of bioapatite
characteristics with high adhesion strength and substitution of therapeutic ions. It can also be used for
processing nanostructured Ca-P coatings on polymeric biomaterials and biodegradable metals and alloys
with enhanced corrosion resistance and biocompatibility.

Statement of Significance

Recent studies have utilized the physical vapor deposition magnetron sputtering (PVDMS) for the depo-
sition of Ca-P and ion-substituted Ca-P thin film coatings on orthopedic and dental implants. This review
explains the effect of PVDMS processing parameters, such as discharge power, bias voltage, deposition
time, substrate temperature, and post-heat treatment, on the surface morphology and crystal structure
of ion-substituted Ca-P and ion-substituted Ca-P thin coatings. It is revealed that coating thickness, sur-
face morphology and crystal structure of ion-substituted Ca-P coatings via PVDMS directly affect the bio-
compatibility and cell responses of such structures. The cell responses determine the osseointegration
between the implant and host bone and eventually the success of the implants.
Ó 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2. Physical vapor deposition (PVD) method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.1. Ca-P and ion-substituted Ca-P coatings via PVD magnetron sputtering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.1. Morphology, crystallinity and Ca/P ratio of Ca-P and ion-substituted Ca-P based coatings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.2. Adhesion strength of Ca-P coating and their applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

⇑ Corresponding author.
E-mail address: cuie.wen@rmit.edu.au (C. Wen).

https://doi.org/10.1016/j.actbio.2019.03.006
1742-7061/Ó 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32 15

2.2. Biological assessments of HA and ion-substituted-HA PVDMS coatings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

2.2.1. Hydroxyapatite (HA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.2.2. Strontium-hydroxyapatite (Sr-HA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.2.3. Silicon-hydroxyapatite (Si-HA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.2.4. Magnesium-hydroxyapatite (Mg-HA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.2.5. Fluorine-hydroxyapatite (F-HA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.2.6. Silver-hydroxyapatite (Ag-HA). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.2.7. Carbonate-hydroxyapatite (C-HA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3. Summary and future prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

1. Introduction increases the risk of infection owing to bacterial adhesion at the

Metallic biomaterials such as commercially pure titanium (CP-
Ti) and some of its alloys are commonly used in healthcare prod-
ucts such as bone plates and screws used in surgery, artificial
joints, and other biomedical implants [1,2]. The spontaneous for-
mation of oxide layers on the Ti alloy surfaces promotes positive
biological cell responses in vivo [3]. However, there are limitations
with bare Ti based alloy implants because of their high corrosion
rate in the physiological environment, resulting in the release of
metal ions and accretion of wear debris. Poor implantation fixation
implantation sites and decreases its osteointegration. Moreover,
metallic implants without surface modification might become
encapsulated by fibrous tissue, which in turn not only prolongs
the healing time, but also leads to implant loosening and eventu-
ally premature failure of implantation [4].
Over the past decade, researchers have increasingly focused on
altering the surface characteristics of biomaterials to promote bone
healing during the early implantation period. Generally, the
surfaces of metallic implants interact with the host physiological
environment; therefore, the surface properties of implants directly

Fig. 1. A comparison of various deposition methods in depositing Ca-P coatings [25–35].

16 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
influence their osseointegration and osseoconductive properties
[5,6]. Hydroxyapatite (HA) is generally considered as a bioactive
coating material to increase the assimilation of implant material
and bone tissue [7]. HA is composed of calcium phosphate (Ca-P)
and has the chemical structure Ca10 (PO4)6 (OH)2); it is the main
chemical constituent of bone tissue (70 wt%). Ca-P formation cre-
ates a strong chemical bond between implants and surrounding
bone tissues [8]. An osteoconductive surface is one that permits
bone growth on the surface or down into the pores, channels, or
pipes of the implant [9]. Any formation of fibrous tissue between
the bone tissue and implant directly influences on osseointegra-
tion. Osseointegration is defined as direct contact between bone
and implant without the formation of fibrous tissue [10,11].
Various techniques have been adapted to develop the Ca-P coat-
ings on biomaterials surface; these include plasma spraying [12],
sol-gel coating [13], electrophoretic deposition (EPD) [14], micro-
arc oxidation (MAO) [15], chemical vapour deposition (CVD) [16],
ion beam assisted deposition (IBAD) [17], pulsed laser deposition
(PLD) [18], and physical vapor deposition magnetron sputtering
(PVDMS) [19]. Fig. 1 shows the advantages and disadvantages of
deposition methods for Ca-P coating. Recent progress on using
PVDMS method exhibited that it is an economical, simple and envi-
ronmentally friendly method to develop ion-substituted Ca-P coat-
ings on Ti and its alloys [20].
The composition, crystallinity, and thickness of Ca-P coatings on
implant surfaces are essential for cell attachment. Several articles
have reported on the effect of amorphous and crystalline Ca-P
coatings developed by various deposition methods on cell
proliferation, cell growth, and cell differentiation [21,22]. Pure
stoichiometrical HA is resistant to resorption and relatively insoluble
when contact with human body fluids; therefore, ion-substituted HA
with similar properties to bone minerals has been explored for
surface modifications [23,24]. In this review, the recent research pro-
gress in the development of Ca-P coating on biomaterials via PVDMS
is elucidated. The influences of surface morphologies, microstruc-
tures, and thicknesses of the various Ca-P and ion-substituted Ca-P
coatings on implant materials are highlighted.
2. Physical vapor deposition (PVD) method
Surface modification of a substrate by physical vapor deposition
(PVD) is an effective way to enhance the biocompatibility of metal
implants [36]. PVD coatings can provide a barrier between the cor-
rosive environment and metal to protect the surface of the sub-
strate, and achieve this protection through the presence of
corrosion-inhibiting chemicals doped in the coating materials. In
order to provide sufficient protection, the coating must be pore
free, uniform, and self-healing, and must increase the bonding
between bone tissue and metallic implant [37]. A variety of meth-
ods are available for the deposition of Ca-P coatings on dental or
Fig. 2. Progress of PVDMS coatings in biomedical applications.
orthopedic implants, such as conversion coatings, electrochemical
plating, organic coatings, anodizing, vapor-phase and hydride coat-
ings techniques. Due to its versatility, environmental friendliness,
and sustainability, PVD technology has received increasing atten-
tion over the recent decade [38]. PVD techniques are often classi-
fied into two groups: evaporation technique and magnetron
sputtering process [39]. This article focuses mainly on PVD mag-
netron sputtering, which has been explored for commercial use.
Earlier research on PVDMS coatings have shown significant con-
tributions towards the wear and corrosion resistance of bone
joints. Fig. 2 shows the progress of PVDMS coatings in biomedical
applications over the last few decades. The TiN coating was devel-
oped in total joint arthroplasty in the 1980s and was utilized for
clinical experiments of knee and hip arthroplasty during the
1990s [40,41].
Such coatings provided protection against wear and corrosion
on femoral components for total knee replacement (TKR) and total
hip replacement (THR) [42]. These previous studies achieved an
increase in the wear resistance of the counterparts of polyethylene
due to high chemical stability and low friction of TiN coating. The
first patent on TiN coating developed by PVD for biomedical appli-
cations was filed in 1997 [43]. However, various in vivo studies per-
formed on TiN coated biomaterials could not provide positive
results, and the research in this area demands further investigation
on the delamination behavior and wear properties [41,44]. In addi-
tion, studies on femoral heads retrieved from revision surgeries
found that the TiN coating was not adequate for such applications
[45]. Consequently, hard coatings including diamond-like carbon
(DLC), aluminum oxide (Al2O3), and silicon carbide (SiC) were
developed via PVDMS for enhanced wear and corrosion resistance
in TKR and THR [46–48]. On the other hand, cobalt-chrome alloy
implant coated with diamond-like carbon (DLC) exhibited low
wear and frictional performance as compared to uncoated sub-
strate [49]. After the early studies, the number of the
commercially-established applications of PVDMS coatings and
investigated material systems for biomedical applications has sig-
nificantly increased. It can be concluded that corrosion and wear
resistance are important research topics in surface modification
of metallic implants via PVDMS methods.
Ca-P coatings such as HA is mostly deposited in the form of thin
coatings via PVDMS for improving the bone formation and enhanc-
ing the bonding strength between the biomaterials and their sur-
rounding bones [50,51]. Another line of research which have
achieved promising results is the substitution of ions in the form
of nanoparticles in HA coatings. Researchers have investigated
the deposition of single and multiple layers of Ca-P based coatings
such as hydroxyapatite (HA) [52–55], silicon-HA [22,56,57],
carbonated-HA [58], strontium-HA [59], fluorine-HA [60],
magnesium-HA [61], and silver-HA [62–66] on implants materials
via PVDMS to attain the desired chemical, physical, biological and
anti-bacterial properties. Moreover, PVDMS technique allows for
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
Fig. 3. Schematic illustration of PVD magnetron sputtering for pure-HA and ion substituted-HA coatings.
the substitution of Ca and P ions on the surface of Ti alloys by
changing the processing parameters, e.g., discharge power, bias
voltage, deposition time, substrate temperature, and post-heat
treatment [53,67–72].
2.1. Ca-P and ion-substituted Ca-P coatings via PVD magnetron
sputtering
PVD magnetron sputtering (PVDMS) was discovered in the
1970s and is known for a high-rate vacuum coating method for
depositing a film on the surface of metallic materials with thick-
nesses in the range of 0.04–3.5 mm [39]. It is a kinetically controlled
process in which the source targets are bombarded with ions
derived from inert gas, and can be considered as a normally played
billiard game with ions and atoms. Positive ions (usually argon gas
is used in industrial processes) are derived through plasma which
ignites between the target (cathode) and substrate (anode). Schil-
ler et al. [73] has reported that electrons escaping from the catho-
dic region are accelerated in the electric field, and strike on the
surface of the target. The kinetic energy is transferred to the target
atoms, which in turn creates a thin film on the surface of the sub-
strate, as shown in Fig. 3. Several composite coatings such as oxi-
des and nitrides can be deposited by PVDMS, if reactive gas (e.g.
oxygen or nitrogen) is added to argon gas.
There were some problems which occurred during sputtering,
such as non-homogeneous ion current distribution across the tar-
get face, realization of desired film characteristics and high film
growth rate only in a non-stable transition mode of discharge, as
well as an increase in resistivity of current path [74]. Despite these
issues, solutions were able to be derived through improvement of
target utilization, reactive process stabilization in transition mode,
long term stable high rate deposition of dielectric films, enhanced
17
properties of coatings and higher rate of deposition. There are sev-
eral advantages accompanying magnetron sputtering: (1) high
purity films; (2) good uniformity on broad metallic surfaces; (3)
high deposition rate; (4) high adhesion strength of coatings; (5)
ease of automation; (6) ability to coat heat-sensitive substrates;
(7) effective coverage of steps and small features; and (8) ease of
sputtering many metals and alloys [39,75]. Owing to the many
advantages of the PVDMS method, calcium phosphate (Ca-P) and
ion-substituted Ca-P coatings on biomaterials for biomedical appli-
cation using this technique have been extensively investigated
[76–79].
2.1.1. Morphology, crystallinity and Ca/P ratio of Ca-P and ion-
substituted Ca-P based coatings
As discussed above, several processing parameters govern the
morphology of pure Ca-P and ion-substituted Ca-P coatings on
metallic implant surfaces during the PVDMS process. These
processing parameters include radio frequency (RF), power (W),
bias voltage (V), sputtering temperature (°C) and time (min), and
post-annealing conditions. Tables 1 and 2 summarize the relation-
ships between the processing parameters of PVDMS and the thick-
nesses of pure Ca-P and ion-substituted Ca-P coatings on CP-Ti and
Ti alloys, respectively.
According to previous studies, the surface morphology plays a
vital role in the achievement of a successful biomaterial [80]. Either
smooth or rough surface morphologies are required in particular
orthopedic cases. PVDMS can deposit uniform and dense coatings
without any bulk porosity or nano/micro cracks on metal implant
surfaces for medical trials. Moreover, PVDMS allows the maintain-
ing of an initial surface roughness of the substrate, which makes
the coatings beneficial in clinical trials where the initial surface
roughness of an implant should not be significantly influenced
18 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32

Table 1
PVDMS process parameters and thickness of Ca-P coatings on different biomaterials.

Substrate Phases Thickness RF power Bias Time Temperature Annealing condition Ref. no.
voltage
CP-Ti HA 20 nm 30 W 50 V 30 min 152 °C No annealing [53]
Si 75 nm 30 W 50 V 120 min 152 °C No annealing
135 nm 30 W 50 V 180 min 152 °C No annealing
100 nm 290 W 100 V 30 min 300 °C No annealing
650 nm 290 W 100 V 120 min 300 °C No annealing
CP-Ti HA 100 nm 30 W – 120 min – No annealing [54]
NiTi HA 100 nm 30 W – 120 min 130 °C No annealing [55]
600 nm 290 W - 300 °C No annealing
Ti6Al4V HA 1200 nm 500 W 25 V 60 min 500 °C No annealing [67]
Ti6Al4V HA 158 nm 150 W – 180 min 60 °C No annealing [72]
Polymethylme-tacrylate HA 144 nm 75 W – 120 min 80 °C No annealing [84]
(PMMA)
Si HA 450 nm 50 W 60 V 360 min 400 °C No annealing [85]
50 W 60 V 360 min 500 °C No annealing
50 W 60 V 360 min 600 °C No annealing
50 W 60 V 360 min 700 °C No annealing
50 W 60 V 360 min 800 °C No annealing
CP-Ti HA 2000 nm 800 W – 240 min – Annealing at 400 °C, 600 °C, 800 °C and 1000 °C for 2 h [86]
Ti6Al4V HA 500 nm 100 W – 60 min – Annealing at 600 °C for 2 h [87]
Ti6Al4V HA 320 nm 150 W – 300 min – Annealing at 500 °C, 600 °C, and 700 °C for 5 h. [88]
Ti6Al4V HA 580 nm 200 W – 120 min 100 °C No annealing [89]
960 nm 300 W 120 min 150 °C No annealing
Si HA 500 nm 130 W – 180 min 60 °C Annealing at 800 °C for 3 h [90]
Ti6Al4V HA 538 nm 150 W – 540 min 156 °C No annealing [91]
CP-Ti HA 170 nm 200 W – 60 min – No annealing [92]
250 nm 200 W – 120 min – No annealing
440 nm 200 W – 180 min – No annealing
CP-Ti HA 690 nm 500 W – 480 min – No annealing [93]
CP-Ti HA 500 nm 150 W – 300 min 500 °C No annealing [94]
Ti6Al4V HA 450 nm 50 W 60 V 360 min 400 °C No annealing [95]
50 W 60 V 360 min 500 °C No annealing
50 W 60 V 360 min 600 °C No annealing
50 W 60 V 360 min 700 °C No annealing
50 W 60 V 360 min 800 °C No annealing

Table 2
PVDMS process parameters and thickness of Ion-substituted Ca-P coatings on different biomaterials.

Substrate Coatings Thickness RF power Bias voltage Time Temperature Annealing condition Ref. no.
CP-Ti, Si Si-HA 700 nm 60 W – 180 min – Annealing at 660 °C for 3 h [22]
Si Si-HA 600 nm 60 W – 240 min 152 °C Annealing at 700 °C for 3 h [96]
CP-Ti Si-HA 250 nm 290 W – 60 min 200 °C No annealing [57]
490 nm 290 W – 120 min 200 °C No annealing
790 nm 290 W – 180 min 200 °C No annealing
CP-Ti Si-HA 600 nm – 50 V 180 min 200 °C No annealing [97]
680 nm 100 V 180 min 200 °C No annealing
CP-Ti C-HA 70 nm 44 W – 5 min – Annealing at 550 °C for 1 h [58]
CP-Ti Sr-HA 204 nm 150 W – 300 min Annealing at 500 °C for 2 h [98]
CP-Ti Sr-HA 321 nm 150 W – 600 min Annealing at 500 °C for 2 h [99]
CP-Ti F-HA 15 nm 110 W – 5 min – Annealing at 600 °C for 2 h [60]
30 nm 110 W – 10 min – Annealing at 600 °C for 2 h
135 nm 110 W – 45 min – Annealing at 600 °C for 2 h
180 nm 110 W – 60 min – Annealing at 600 °C for 2 h
315 nm 110 W – 105 min – Annealing at 600 °C for 2 h
540 nm 110 W – 180 min – Annealing at 600 °C for 2 h
CP-Ti Mg-HA 100 nm 130 W – 180 min No annealing [61]
CP-Ti Ag-HA 500 nm 500 W – – – No annealing [62]
Ti6Al4V Ag-Si-HA 250 nm 50 W 60 V – 700 °C No annealing [63]
Ti6Al4V Ag-HA 250 nm 0.9 W 60 V – 700 °C No annealing [64]
CP-Ti Ag-HA 10 nm 10 W – – – Annealing at 300 °C, 400 °C, 500 °C, and 700 °C for 2 h [65]
20 nm 30 W – –
ZrO2 Ag-HA 700–1000 nm 150 W – – – Annealing at 800 °C for 3 h [100]

[53–55,58,61,70]. Meanwhile, surface porosity of Ca-P coatings is
essential for bone growth; therefore it is important to control
porosity during the coating process. A micro-porous structure
and multi-sediment layer were observed on coating surfaces in
attaining bioactive implants [81,82]. In general, the porosity of
coatings is controlled through adjusting the working gas pressure
and substrate temperature during PVDMS process [83].
Surmeneva et al. [53] reported that the surface morphology of
coatings could be significantly influenced through altering the
processing parameters. It was observed that sphere-like islands
of Ca-P coatings produced by RF magnetron sputtering showed
very smooth and dense morphologies by using processing param-
eters of 290 W RF power, 100 V DC bias, 180 min deposition time,
constant working pressure, and argon gas. The SEM images and
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
Fig. 4. SEM images and histograms of the grain size distribution of the HA coating deposited via PVDMS at 290 W for (a,b) 15 min; and (c,d) 180 min. Reproduced with
permission from [53].
histograms of the grain size distribution of the HA coatings depos-
ited via PVDMS at 290 W are shown in Fig. 4(a) and (b) for 15 min
and Fig. 4(c) and (d) for 180 min, respectively. It can be seen that
the grain size was 65 nm at 15 min, and increased to 105 nm at
180 min. The surface roughness and morphology of HA coatings
can be changed if annealing is applied. The surface roughness,
thickness, and morphology of HA coatings dependent on the sput-
tering time and annealing temperature [86,101–104]. The conver-
sion from amorphous to crystalline coatings depends on the
annealing environment (presence or absence of water vapor) and
temperature in the chamber [102], for example, annealing at
450 °C in the presence of water vapor and at 500 °C in the
absence of water vapor have been reported for the development
of Ca-P coatings with 60–70% crystallinity which is normally
required for the coatings [101,105,106]. If the temperature was
excessive, cracks could be seen at the interface and delamination
may occur [107]. The increasing propagation of cracks and failure
of the interface at high temperature are attributable to the recrys-
tallization and are related to the change in the HA specific volume,
which results coating stresses.
PVDMS provides the development of Ca-P and ion-substituted
Ca-P coatings of either amorphous or crystalline structure of cer-
tain phase compositions. The crystallinity and Ca/P ratio of the
coatings affect their degradation behavior in vitro [53,59,68,70].
In general, amorphous phase or calcium phosphate compounds
form when using partially crystalline targets in RF magnetron
sputtering [53,68,70,84,108–113]. Therefore, it is important to con-
vert the amorphous coatings into crystalline HA or ion-substituted
19
HA of different degrees of crystallinity using annealing. Bramowicz
et al. [85] developed an HA coating using the MS method at con-
stant RF power of 50 W, negative bias voltage of 60 V, and sputter-
ing time of 360 min at different temperatures of 400, 500, 600, 700,
and 800 °C. It was observed that circular cavities around 430 nm in
diameter were exhibited at 400 °C and the average distance
between cavities was around 720 nm, as shown in Fig. 5(a). At
500 °C, the number of cavities increased and their average size
decreased to about 180 nm, with an average distance between
cavities reduced to around 500 nm (Fig. 5(b)). The average grain
size of the coating increased from 190 to 300 nm by increasing
the deposition temperature from 600 to 800 °C, as shown in
Fig. 5(c), (d), and (e). It can be concluded that the surface topogra-
phy of the HA coatings exhibited different length scales and diam-
eters of cavities; these were individually affected by the deposition
temperature.
Annealing in situ at 550 °C [58], and 297–527 °C [54,55], and
post-annealing at different temperatures of 320–700 °C in water
vapour, vacuum or air, and inert gas improved the crystallinity of
the coatings [68,86,87,114–116]. Crystalline HA coatings were
achieved with in situ annealing temperatures of 500 and 600 °C,
and also a hybrid HA coating at 700 °C [85,88]. The metallic
substrate was heated up to 700 °C under the influence of the RF-
plasma in all experiments. The temperature of the substrate was
controlled with a Pt/PtRh thermocouple which was placed close
to the substrate in the deposition chamber [54]. As-deposited HA
coatings with adequate crystallinity were developed through the
PVDMS method [53–55,117]. Fig. 6 shows the XRD patterns of an
20 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32

Fig. 5. AFM images and 3D projections of marked areas of HA coatings deposited via PVDMS at different temperatures. Reproduced with permission from [85].

Si-HA coating produced via PVDMS at different sputtering times.

Fig. 6. XRD patterns of Si-HA coatings fabricated via PVDMS at different sputtering
times. Reproduced with permission from [57].
The high intensity of the (0 0 2) peak at 25.78 °C 2H indicated
the preferred crystallographic orientations of the Si–HA film [57].
The (0 0 2) texture is a common phenomenon when PVDMS is used
[53,54,58,70,88,89,115]. HA coatings with highly thin crystalline
structures at the nano-meter scale were developed using PVDMS
[52,90].
The Ca/P ratio of Ca-P coatings is important in biomedical appli-
cations because natural bone matrix is mostly made up of a com-
posite material incorporating Ca-P. This similarity in the
chemical compositions of Ca-P coatings and natural bone offers
direct chemical bonding between surface coating and bone tissue.
According to representative energy dispersive X-ray spectroscopy
(EDS) and X-ray photoelectron spectroscopy (XPS) analyses, Ca-P
coatings typically exhibited oxygen, carbon, calcium, and phosphor
after RF magnetron sputtering [54,55,91]. An EDS graph analysis of
PVDMS-deposited coatings showed a homogeneous distribution of
Ca and P on the coating surface, exhibiting no segregation, which is
generally responsible for the formation of undesired second phases
[84]. The Ca/P ratio is influenced by the applied control parameters
during the deposition process [67,93,118]. The ratio Ca/P = 1.67 as
the average HA stoichiometric can be developed by the PVDMS
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
method [53,119]. Generally, the stoichiometry formation of HA
coatings from PVD magnetron sputtering of multiple targets was
varied from the bulk target. Snyders et al. [120] reported that the
phenomenon of Ca/P ratios from 1.53 ± 0.03 to 1.83 ± 0.03 exhib-
ited the formation of CaO and, Ca3(PO4)2 phases. The target compo-
nents, e.g. hydrogen, oxygen, and hydroxide, could not be entirely
transferred to the surface of the materials due to low pressure in
the vacuum.
Generally, high purity coatings can be achieved by PVDMS
[15,18]. However, the composition of coatings could be changed
from the composition of bulk target, depending on the deposition
parameters and the sputtering system [121]. In particular, the vari-
ations in Ca/P ratio between the sputtered coatings and the HA tar-
gets is the probable cause of the significant loss of P ions, or
preferential deposition of Ca ions, which may be pushed off before
attainment on the substrate surface or be re-sputtered out of the
growing films by incoming ions [68,86]. Another influence of the
Ca/P ratio is on the variation of sputtering rates for Ca and P from
targets. It was reported that there was an increase in Ca/P ratios
when the annealing temperature was increased [122]. Ergun
et al. [123] confirmed that osteoblast adhesion increased when
the Ca/P ratio was maximized (up to 2.5) in nano-particulate
Ca-P formulations, and this is an important step for consequent
osteoblast function such as new bone formation. Amorphous coat-
ing structures were observed at low deposition temperatures; the
Ca/P ratio increased from 1.41 to 1.69 with an increase in temper-
ature [85]. Feddes et al. [124] reported the effect of bias voltage on
the Ca/P ratio and coating crystallinity. It was observed that
calcium was considered as positively charged ions (i.e., Ca+ and
Ca2+) and radicals (i.e., CaO+) generated in the plasma. Further-
more, higher fluxes of CaO+ cations onto the surface were caused
by higher negative substrate bias and it became more difficult for
(PO4)3 anions to reach the substrate surface, resulting in higher
Ca/P ratios [97]. Researchers reported that Ca/P ratio increased
from 1.53 to 3.88 when the negative bias voltage increased from
50 to 100 [53].
Ozeki et al. [59] reported that post-annealing is required to
increase the crystallinity of Sr-substituted HA coatings after
PVDMS. Annealing of Sr–HA coatings may influence the
(Sr + Ca)/P ratio, surface morphology, adhesion strength between
the coating and substrate, and absence or presence of cytotoxic
Sr(OH)2 and CaO. The Ca/P and (Ca + Sr)/P ratios for deposited
coatings were recorded to be around 1.18 and 1.26, respectively.
Consequently, during the sputtering process, more Ca atoms were
sputtered compared to Sr, due to differences in their atomic
weights. Therefore, the Sr/(Sr + Ca) ratio after deposition tended
Fig. 7. SEM images showing the morphologies of the rapture surfaces of coated samples: (a) adhesive failure and (b) cohesive failure. Reproduced with permission from [127].
21
to be lower than that of the target, and the Sr ratio can be increased
through the post-annealing process [59,98].
2.1.2. Adhesion strength of Ca-P coating and their applications
The adhesion strength between Ca-P coating and implant (such
as CP-Ti, TiNi, and polytetrafluorethylene (PTFE)) determines the
overall success of the implant [54,125]. It plays an important role
in achieving high performance and long term fixation of the
implant in the physiological environments. Insufficient adhesion
strength of Ca-P coatings leads to adverse tissue responses and
micromotion of implant, and ultimately production of debris parti-
cles [126]. The morphology of rupture surfaces after cohesive and
adhesive failure of Ca-P coating are shown in Fig. 7 [127]. There
are various coating processes such as dip coating process [128],
pulsed laser deposition [129], magnetron sputtering [130], hot
iso-static pressing [131], plasma spray [132], sol-gel [133] and
thermal spray [134]. These processes produce Ca-P coatings with
different adhesion strength. Fig. 8 represented the adhesion
strengths of HA coatings produced by different methods. It can
be seen that the coatings developed by magnetron sputtering
method exhibited an adhesion strength of 80 MPa, which is higher
than that of hot iso-static pressing (14 MPa), pulsed laser deposi-
tion (16 MPa), MAO process (44 MPa), plasma spray (25 MPa),
sol–gel (26 MPa), dip coating (30 MPa), and thermal spraying
(33.2 MPa) [128–134].
Moreover, a linear relationship was observed between the aver-
age surface roughness of implant surface and the adhesion
strength of the coatings [135,136]; thus, highly roughened implant
surfaces exhibited high adhesion strength of HA coatings in
contrast to smooth surfaces [137]. Pre-treatment techniques are
commonly used to increase the surface roughness prior PVDMS
HA coating [54,138–140]. Various pre-treatment techniques such
as electron beam, glass, sand, and ceramic microspheres blasting,
acid chemical etching, and abrasive paper grinding are effective
processes for roughening implant surfaces. Nevertheless, pre-
treatments are not the only approach to assure high adhesion
strength coatings on implant surfaces. Recent studies reported that
the adhesion strength of the outer layer (e.g., nitrides, oxynitrides,
carbides, and carbonitrides) coatings to the implant surface could
be enhanced by deposition of a thin interlayer between substrate
and outer layer coatings and the interlayers can be Ti [141–143],
or Ta [144,145], or AlN [146], or SiC [147]. For bioactive HA coat-
ings, various types of interfacial layers were reported such as Ti
[125,148], TiO2 [122,149–151], SiO2 [152], SiC [153], TiN [154]
and TiAlVN [155] (Fig. 9). It can be seen that studies were focused
on the deposition of an interlayer of TiO2 nanotubes between the
22 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32

Fig. 8. The adhesion strength of HA coatings produced by different methods.

Fig. 9. Schematic of different types of interlayer coatings on implant surfaces before HA coating.

Fig. 11. Fluorescence micrographs of cell nuclei staining and actin cytoskeletal
organization of osteosarcoma cell growth on HA coatings deposited at different
temperatures (°C). Reproduced with permission from [95].

Over the last decade, the mechanical properties of Ca-P coating

Fig. 10. Cell viability of uncoated and HA coatings formed at different temperatures
after 3, 5, and 7 days of culture. Reproduced with permission from [95].
implant substrates and the HA coatings developed by PVDMS. It
can be concluded that pre-treatment techniques and an interfacial
layer particularly a TiO2 nanotubular layer on the implant surfaces
can significantly increase the adhesion strength of the PVDMS
pure-HA and ion-substituted HA coatings.
have received increasing research interest to achieve satisfactory
bone healing in the early stage of implantation. The mechanical
properties of Ca-P coatings are affected by their crystallinity. An
amorphous structure of Ca-P coating is not desired because it
exhibited a high dissolution rate in SBF [53,70]. Therefore, it is
important to convert the amorphous phase to a crystalized struc-
ture or ion-substituted HA coatings with certain degrees of crys-
tallinity, and a crystalline HA coating can be achieved via either
annealing or depositing at high temperature (700–800 °C).
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
2.2. Biological assessments of HA and ion-substituted-HA PVDMS
coatings
Cell behaviors within a metal implant biomaterial are very
complex chemical as well as biological procedures, associated with
various surface properties [156]. It was revealed that the biological
properties of Ti and its alloys, polymers and Mg alloys, were con-
siderably improved by a thin Ca-P coating on the substrates
[84,94,157]. A pure HA stoichiometry is resistant to resorption
and relatively insoluble when in contact with human fluids; there-
fore, ion-substituted Ca-P coatings with similar properties to bone
minerals are preferred [23,24]. Strontium (Sr), manganese (Mn),
calcium (Ca), phosphates (PO34 ), and magnesium (Mg) substitu-
tions for silicates (SiO44 ) can be found in human mineralized
tissues [58,98,158]. This new approach of using ion-substituted
Ca-P coatings created via PVDMS is beneficial for biomedical
applications, as discussed below.
2.2.1. Hydroxyapatite (HA)
A previous study reported that the biological properties of Ti
and its alloys were considerably improved by thin Ca-P coating
[94]. Vladescu et al. [95] assessed the in vitro cell viability, which
was analyzed after 3, 5, and 7 days of culture with a human
osteosarcoma cell line (MG-63). The results are presented in
Fig. 10. It was revealed that after 7 days of culture, the cells showed
significant attachment, spreading as well as growing on the coating
surface at various deposition temperature levels. Fig. 11 shows flu-
orescence micrographs of the cell nuclei staining and actin
cytoskeletal organization of the osteosarcoma cell growth on the
HA coatings deposited at different temperatures (°C). It can be seen
that a higher density of cell nuclei (blue shading) was observed on
the Ca-P coating developed at 700 and also 800 °C compared to the
coatings deposited at 400, 500, and 600 °C, with a thick cytoskele-
tal F-actin and enhanced proliferation. Furthermore, numerous
cells with a spindle shape attached well and spread out over the
entire coated surface area, showing suitable biocompatibility. This
Fig. 12. Fluorescence microscopy (SYTO-9) showing morphologies of HA coatings at different thicknesses after 3 days of culture. Reproduced with permission from [92].
23
behavior is due to the increase in deposition temperature, which
resulted in an increase in the surface roughness of the coating
[95]. After implantation, the first contact of the implant surface
area is with proteins, which are referred to as promoters of the pro-
liferation and spreading of osteoblasts, resulting in a reliable
implantation [159]. The proteins stick much better to a rough
and porous surface because of a larger surface–cell interface [160].
Surmeneva et al. [92] conducted an in vitro assay of the HA coat-
ings with dental pulp stem (DPS) cells. Fig. 12 shows fluorescence
micrographs of the cell morphologies after 3 days of culture on HA
coatings with different thicknesses. Compared with the uncoated
Ti surface, enhanced cell attachment as well as cell spreading were
observed on the Ca-P coated surface areas, indicating significant
cell proliferation and matrix synthesis [92]. Moreover, after 3 days
of DPS cell culture, Ca-P coatings with different thicknesses
showed a similar effect in promoting DPS cell attachment and pro-
liferation. Fluorescent staining showed inadequate cell attachment
and non-homogeneous distribution of DPS cells on the Ti surface,
as they exhibited a tendency to accumulate into large cell clusters.
In comparison, DPS cells seeded on the Ca-P coating were homoge-
neously dispersed, well spread out, and also flattened with numer-
ous filopodia from the cell membrane layers.
Nowadays, HA film as protective surface layers on the surface of
biodegradable magnesium (Mg) alloys has attracted significant
attention. HA coatings on Mg alloys can improve both their corro-
sion resistance and biocompatibilty [157,161–163]. Kleinhans et al.
[157] investigated the in vitro performance of nanostructured HA
coatings deposited on a biodegradable AZ91D Mg alloy using
PVDMS. The nanostructured HA coating with a thickness of
700 nm was demonstrated to significantly improve the cell behav-
ior as compared with the uncoated Mg alloy. Moreover, an
enhanced initial cell attachment of human mesenchymal stem
cells (hMSCs) and a higher ALP level were observed on a Ca-P
coated surface after 1 day of cell culture (Fig. 13). Mukhametka-
liyev et al. [161] investigated the corrosion behavior, biomineral-
ization and bioactivity of biodegradable AZ91 Mg alloy with a
24 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32

Fig. 13. Cell adhesion on (a, b) uncoated and (c, d) HA-coated AZ91D alloy at day 1 by fluorescence staining for vinculin (green) and actin (red) that are components of focal
adhesions. Cells were either kept in (a, c) proliferation medium, or (b, d) osteogenic medium. Reproduced with permission from [157]. (For interpretation of the references to
colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 14. AFM images of annealed Sr–HA coatings at 500 °C with different Sr concentrations: (a) 5% Sr-HA; and (b) 13% Sr-HA. Reproduced with permission from [99].

nanostructured HA coating using PVDMS. It was observed that the
HA coating led to a significantly reduced corrosion current density
(icorr) from 80.88 to 0.35 lA/cm2. The HA coating also enhanced the
polarization resistance (Rp) in vitro, which confirmed the ability of
the HA coating in decreasing the corrosion rate of the Mg alloy.
Moreover, an HA coating can promote the Ca-P precipitation on
the Mg surface in vitro. Thus, it can be concluded that HA coating
on Mg alloys via PVDMS can not only effectively improve the bio-
compatibility, but also slow down the corrosion rate of Mg alloys in
the physiological environment.
2.2.2. Strontium-hydroxyapatite (Sr-HA)
Strontium (Sr) has recently drawn attention in view of it being a
‘‘bone-seeking element” of biological relevance. Sr substitutions
are widely investigated because it is used as a treatment for osteo-
porosis. The introduction of an Sr element as a drug can reduce
bone resorption by inhibiting the number of active osteoclasts
and boosting the pool of active osteoblasts [24,59,164]. The
influence of Sr on osteoblasts is because it is directly involved with
their Ca-sensing receptors, therefore increasing the cell division to
interact with the mitogenic signals in the proteins kinase [98]. Sr
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
Fig.15. TEM rings showing the spotty nanocrystalline structure of Si-HA coating.
Reproduced with permission from [57].
treatment of osteoporosis resulted in a dose-dependent increase in
the mechanical strength and architecture of bone [165].
In vitro performance of Sr-substituted HA depends on its con-
centration; when there is an increase in the Sr concentration, the
osteoclast proliferation decreases [166]. The optimum concentra-
tion of Sr substitution has been reported to be around 3–7% [98].
Boyd et al. [99] deposited Sr–HA coatings onto a silicon surface
using the PVDMS method. Fig. 14 shows AFM images of Sr–HA
coatings annealed at 500 °C with different Sr concentrations: (a)
5% Sr–HA; and (b) 13% Sr–HA. It was observed that the surface
roughness (Ra) increased with an increase in the Sr concentration
from 5% to 13%.
The annealed high-purity 13% Sr–HA coating could be expected
to improve both in vitro and in vivo performance, as compared to
pure HA [99]. It has also been reported that standard Ca–P materi-
als (namely HA) offer bioactivity due to the actions of free Ca2+ ions
Fig. 16. SEM images showing the cellular morphology of human osteoblast-like
cells (MG-63 cell line) growth after 1 and 7 days culture on uncoated and coated
with Si-HA coating via PVDMS. Reproduced with permission from [97].
25
[167]. HA coatings with increased percentage of Sr content, such as
the annealed Sr-HA surface are more prone to dissolution in the
physiological environment due to the increased ionic radius of Sr
and the associated lattice expansion [168–170]. This results in an
increase in the lattice parameters, with the Ca site thought to be
the preferred site for Sr substitution [23]. These factors play a vital
role both in vitro and in vivo through improving the cell differenti-
ation, osteoblast activity (proliferation) and reducing osteoclast
activity [171].
2.2.3. Silicon-hydroxyapatite (Si-HA)
The silicon (Si) element plays an important role in bone growth.
Hence, the addition of Si in the HA matrix (in the form of silicates)
is expected to successfully promote the bioactivity of implant
materials [166]. The significant influences of Si in HA coatings
are that it decreases the HA crystal size, promotes the formation
of amorphous phases, increases its solubility, makes the surface
more electronegative, and increases the adhesion strength [166].
Surmeneva et al. [57] developed a nanostructured Si–HA coat-
ing on a CP-Ti substrate through the PVDMS process using different
parameters such as RF power (290 W), substrate temperature
(200 °C), and time (60 min). It was observed that the nanocrys-
talline structure of Si–HA coatings exhibited amorphous regions,
as shown in Fig. 15. After being implanted, the crystalline and
amorphous structures were progressively resorbed inside the
human body, and induced new bone formation by releasing Ca
and P ions into the biological medium. The amorphous structure
of the coating increased with increasing the percentage of Si con-
tent [172].
Pichugin et al. [56] reported that, without increasing the Si con-
tent of coatings, the required crystallinity can be achieved by a
post-deposition annealing process. It was suggested that annealed
coatings showed suitable biological activity and surface mineral-
ization. In vitro studies have shown that Si–HA coatings created
via PVDMS enhanced cell proliferation, osteoblast attachment,
and cell differentiation [56,57,96].
Surmeneva et al. [97] assessed biocompatibility by cell culture
with human osteoblast-like cells (MG-63 cell line) on Si–HA coat-
ings. In vitro assessment revealed that the cells preserved their nat-
ural spindle-like morphology and spread out well, as shown in
Fig. 16. The cells covered the entire HA-coated surface and all sam-
ples exhibited rapid bonding of cells on the surface area, showing
no significant toxicity.
Fig. 17. SEM image showing the morphology of Si-HA coating after immersion in
SBF for 14 days. Reproduced with permission from [96].
26 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
Fig. 18. Osteoblast proliferation on Ti substrates coated with (a) HA; (b) Mg5%-HA after cell culture for 4 days. Reproduced with permission from [61].
Fig. 19. GIXRD spectra of F-HA coatings deposited at various times: (a) 45 min, (b)
60 min, (c) 90 min and (d) 180 min. Reproduced with permission from [60].
Thian et al. [96] investigated the in vitro biocompatibility of sil-
icate, consisting of HA coatings in SBF. Fig. 17 shows the surface
morphology of the Si–HA coating after immersion in SBF. After
14 days of immersion, a dense and uniform porous, lamellar-like
structure was noted. Si–HA coatings created via PVDMS have the
ability to form carbonate-containing Ca-P, which could be a good
candidate for hard tissue replacement [96].
2.2.4. Magnesium-hydroxyapatite (Mg-HA)
The magnesium (Mg) element is used as a dopant because it is
found in small concentrations in human bone (0.72 wt%), enamel
(0.44 wt%), and dentin (1.23 wt%) [166]. Mg influences the
metabolic activity of bone growth, osteoblasts, and osteoclast cell
activity, and Mg deficiency can cause fragility or osteopenia
[173]. Substitution of calcium (Ca) for Mg in the crystal lattice
increases HA solubility and crystallinity [174].
Hong et al. [61] studied Mg-doped HA (Mg–HA) coatings depos-
ited on CP-Ti by the PVDMS process using RF power of 130 W for
180 min. Biological assessment of the sputtered Mg–HA coating
showed high cell viability and osteoblast adhesion, but no signifi-
cant difference was observed in cell attachment as compared to
HA, as shown in Fig. 18. Moreover, the Mg–HA coating was found
to be highly amorphous in nature and induced fast dissolution,
leading to similar biological responses as with HA coatings.
2.2.5. Fluorine-hydroxyapatite (F-HA)
Fluorine (F) is required for the prevention of dental caries and
osteoporosis treatment. The HA crystal lattice shows lower
symmetry as compared to fluorapatite (FA); therefore, it has lower
solubility and higher stability in body fluids [23,175]. In vitro, F
content showed a positive influence on cell proliferation and cell
differentiation [158].
Lopez et al. [60] produced an F-substituted HA (F–HA) coating
on Ti and Si surfaces using PVDMS with different times. Before
F–HA deposition, heating of the substrates was carried out at dif-
ferent temperatures of 100, 200, and 300 °C to attain a crystalline
coating. Suitable crystallinity of F–HA thin coatings can be
achieved by pre-deposition heating at 300 °C [60]. As shown in
Fig. 19, the grazing incidence X-ray diffraction (GIXRD) pattern
exhibited disordered nanocrystalline HA phases at a short sputter-
ing time of 45 min; whereas a highly crystallized F–HA coating was
achieved by increasing the time to 180 min, as shown in Fig. 19(d).
The GIXRD pattern exhibited weak diffraction peaks of (1 0 0),
(0 0 2), (1 2 1), and (0 0 3) HA phases at a lower film thickness
(135 nm); these peaks were superimposed on the broad peaks,
indicating the initial stage of the crystallization process. The broad
peaks were continuously decreased by increasing film thickness,
although the crystalline contribution became dominant [60].
Generally, for an ion substitution in HA, fluoride decreased the
solubility of the produced apatite due to increases in crystallinity
and crystal size at a concentration less than 20% [23]. The formula
Ca10(PO4)6(OH)F was shown to give the best stimulating influence
on cell proliferation and differentiation as compared with higher
and lower amounts of F [176]. F–HA has also been shown to have
antibacterial properties compared with stoichiometric HA [177].
2.2.6. Silver-hydroxyapatite (Ag-HA)
In biomedical applications, silver (Ag) has been known for its
antibacterial properties and also its ability to increase osseointe-
gration [62]. Researchers have recently given attention to
Ag-containing HA (Ag–HA) composite coatings because the combi-
nation of Ag and HA in coatings provided bacterial inhibition and
enhancement of the osteoblast functions of implant materials
[178,179]. Incorporation of Ag ions into HA has been investigated
as a possible solution to infection, with promising results
[180,181]. Ivanova et al. [62] studied the physico-chemical charac-
terization of Ag–HA coatings acquired via PVDMS. The thickness of
the deposited Ag–HA coatings was 500 ± 30 nm. Fig. 20 presents
SEM images of a typical cross-section view, and the morphology
possesses the columnar structure of the Ag–HA coating. Moreover,
it was also observed that the content of Ag in HA coatings was
lower than the initial Ag concentration in the sputter targets
[62]. It was considered that the PVDMS deposition parameters
had significant effects on Ag concentration.
It was reported that the concentration of released silver ions (up
to 3 wt%) in HA coatings can promote antibacterial properties
 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32 27

Fig. 20. SEM micrographs of Ag-HA coatings deposited on (a) CP-Ti; and (b) Si. Reproduced with permission from [62].

Fig. 21. Differentiation of human mesenchymal stem cells (hMSCs) on CHA–Q deposited films versus control materials with and without osteogenic factors: (A) intracellular
ALP activity after culture for 7, 14, and 21 days; (B) quantification of relative ALP activity after 21 days’ culture. Reproduced with permission from [58].

without showing significant cytotoxicity [62,66,182,183]. Park
et al. [100] studied Ag-doped HA coatings deposited on an Si sub-
strate via the PVDMS method. It was found that Ag+ ions in the HA
were replaced by Ca2+ ions. Therefore, the modulus of elasticity
and hardness decreased with an increase in the Ag ion concentra-
tion. Ciuca et al. [64] developed Ag-doped HA coatings deposited
on a Ti6Al4V substrate via PVDMS at RF power of 0.9 W, bias volt-
age of 60 V, and substrate temperature of 700 °C. It was observed
that the incorporation of Ag ions (2.1 wt%) was sufficient to pro-
mote an antifungal effect in the HA coating, without formation of
the stoichiometric HA phases.
Badea et al. [63] investigated the influence of different levels of
Ag content in HA coatings deposited on a Ti6Al4V alloy using
PVDMS at RF power of 50 W, bias voltage of 60 V, and substrate
temperature of 700 °C. It was revealed that HA with the incorpora-
tion of Ag (0.7 wt%) improved the protection from bacterial attack
28 M. Qadir et al. / Acta Biomaterialia 89 (2019) 14–32
(such as Streptococcus pyogenes, Staphylococcus aureus, and Sal-
monella typhimurium) without any effect on microstructural,
micro-chemical, or anticorrosive properties [63].
2.2.7. Carbonate-hydroxyapatite (C-HA)
Carbonate is highly diffusing in biological apatite [184]. In fact,
biological apatite is involved in carbonated apatite (CA), with
different concentrations of carbon dioxide (CO2) from 3.5 to 7.4
(wt%). Sima et al. [58] developed a carbonated HA coating on a
fused Si substrate (CHA–Q) using PVDMS at RF power of 44 W
for a time of 5 min. High adhesion strength of the coating was
attained with a Ca/P ratio of 1.8. A post-deposition annealing
process was used to increase the degree of crystallinity to 90% of
the as-deposited amorphous coating. Sputtered C–HA coatings
showed high proliferation and viability of osteoblasts without
any cytotoxic effect on bone cells [58]. Fig. 21(a) shows the differ-
entiation of human mesenchymal stem cells (hMSCs) with and
without osteogenic factors after cell culture for 7, 14, and 21 days.
To further support this observation, relative alkaline phosphatase
(ALP) activity was observed after 21 days; cells were grown on
CHA–Q due to dexamethasone in contrast to Ti, and biomet
eternity (BE) (Fig. 21(b)). The ALP activity on CHA–Q was four
times greater than that of industrial BE with and without
osteogenic factors.
3. Summary and future prospects
Coatings based on ion-substituted calcium phosphate (Ca-P)
have attracted great attention over the last past for dental and
orthopedic applications. PVDMS is a recently explored technique
for the deposition of pure Ca-P and ion-substituted Ca-P thin
coatings on the surface of metallic implants. This method is
cost-effective and can be used for the preparation of dense,
homogenous, and high-adhesion-strength thin coatings. Research-
ers have recognized various governing aspects which directly
determine the chemical and physical properties of ion-
substituted Ca-P coatings by PVDMS. These aspects include
discharge power, bias voltage, deposition time, substrate tempera-
ture, and post-deposition annealing treatment.
The osseointegration and biocompatibility of metallic implants
can be improved by changing the microstructure, surface morphol-
ogy, and thickness of the Ca-P and ion-substituted Ca-P coatings. A
reduced dissolution rate was observed for coatings with higher
crystallinity (or a lower fraction of amorphous phases). In addition,
amorphous Ca-P thin coatings rapidly induce bone formation,
while releasing Ca ions. It was observed that the topography and
surface chemistry of amorphous HA coatings and ion-substituted
HA coatings significantly increase the cell attachment, but
obstructs the growth of cells attached to the coating surface areas
because of a cytotoxic effect. At the same time, low-crystalline HA
coatings exhibit lower rates of osteogenic cell proliferation as com-
pared to highly crystalline HA coatings developed on a Ti surface.
There are still concerns on the actual benefits of ion-substituted
coatings, particularly the assessment of the advantages resulted
from ion incorporations. The influence of ion substitution is often
unclear because the substitution of ions in the HA lattice is not suf-
ficiently investigated. Under the same PVDMS parameters, no com-
parative study has been carried out on the properties of Ca-P and
ion-substituted Ca-P coatings. There are also other issues related
to PVDMS produced ion-substituted HA coatings for clinical
applications such as that the results reported by different groups
of researchers were based on different PVDMS parameters and
annealing conditions, which pose difficulties for analysis.
Although, PVDMS produced ion-substituted HA coatings
could improve the bone cell attachment, proliferation, growth,
osseointegration and antibacterial properties. The above-mentioned
pitfalls are the barriers to their commercialization. A comprehensive
understanding of the detailed chemical, morphological and structural
characteristics of ion-substituted Ca-P coatings is required. Future
research directions include in vivo assessments on the ion-
substituted HA coatings and standard PVDMS procedures to achieve
the optimal surface properties of coatings.
Overall, PVDMS allows a close reproduction of bioapatite
characteristics with high adhesion strength and incorporation of
therapeutic ions. This process can also be used for processing
nanostructured ion-substituted Ca-P coatings on polymeric bioma-
terials and biodegradable metals such as Mg-based alloys with
enhanced corrosion resistance and biocompatibility. These fea-
tures are promising and can broaden the spectrum of the clinical
applications in coming years.
Acknowledgements
The authors acknowledge the financial support for this research
by the National Health and Medical Research Council (NHMRC),
Australia, through grant GNT1087290; and the Australian Research
Council (ARC) through the discovery grant DP170102557. YL is also
supported through an ARC Future Fellowship (FT160100252).
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