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Accepted Manuscript
“The return of ceramic implants”: Rose stem inspired dual layered
modification of ceramic scaffolds with improved mechanical and
anti-infective properties
Chen Li, Fanrong Ai, Xinxin Miao, Hang Liao, Fengshun Li,
Mingzhuo Liu, Fen Yu, Lina Dong, Ting Li, Xiaolei Wang
PII:
DOI:
Reference:
S0928-4931(17)34684-2
doi:10.1016/j.msec.2018.08.044
MSC 8838
To appear in:
Materials Science & Engineering C
Received date:
Revised date:
Accepted date:
1 December 2017
6 July 2018
20 August 2018
Please cite this article as: Chen Li, Fanrong Ai, Xinxin Miao, Hang Liao, Fengshun Li,
Mingzhuo Liu, Fen Yu, Lina Dong, Ting Li, Xiaolei Wang , “The return of ceramic
implants”: Rose stem inspired dual layered modification of ceramic scaffolds with
improved mechanical and anti-infective properties. Msc (2018), doi:10.1016/
j.msec.2018.08.044
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ACCEPTED MANUSCRIPT
“The return of ceramic implants”: rose stem inspired
dual layered modification of ceramic scaffolds with
improved mechanical and anti-infective properties
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Chen Lia,#, Fanrong Aib,c,e,#, Xinxin Miaoa, Hang Liaoa, Fengshun Lib,
a
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Mingzhuo Liud, Fen Yu b, Lina Dong b, Ting Lib & Xiaolei Wanga,b*
Department of Orthopedic Surgery, The Second Affiliated Hospital of
b
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Nanchang University, Nanchang, Jiangxi, 330006, China.
Institute of
330031, China.
c
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Translational Medicine, Nanchang University, Nanchang, Jiangxi,
School of Mechanical & Electronic Engineering,
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Nanchang University, Nanchang, Jiangxi, 330031, China. d Department of
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Burns, The First Affiliated Hospital of Nanchang University, Nanchang,
Jiangxi, 330006, China. eKey Laboratory of Lightweight and high
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strength structural materials of Jiangxi Province, Nanchang University,
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Nanchang 330031, China. #These authors contributed equally to this
work.* Address correspondence to E-mail: wangxiaolei@ncu.edu.cn
Abstract
Nowadays, traditional ceramics for bone implants have considerably
replaced by metal based biomedical materials, attributing to the friability
of
ceramics.
However,
ceramic
implants
possess
excellent
biocompatibility and longtime abrasion resistance. They should be more
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desirable for long-term uses of implants in case their fragility had been
overcome. In the present work, inspired from natural rose, a
dual-layer-modified ceramic scaffold was constructed by coating a
superplastic layer of isocyanate (ISO) resin and a nano Zinc Oxide
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(nano-ZnO) layer on the ceramic scaffold. The ISO resin modification
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layer with 1 mm thickness, improved the mechanical properties of
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ceramic implants 2-3 times, and protect the ceramic implants from broken
even drop from 1 meter high. Moreover, such dual layered modification
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exhibited broad spectrum antibacterial behavior. In vivo biocompatible
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studies demonstrated that there was no obvious noticeable tissue damage
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in all major organs of mice after the implant surgeries.
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Keywords: Surface modification; Ceramic implants; 3D printing;
Antibacterial activity; Biomedical engineering
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1. Introduction
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Great progresses of biomaterials for bone implants has been made in
the past decades [1-4]. According to the bioactivities of biomaterials,
artificial bone implants can be mainly divided into three types: biotolerant
materials (titanium, tantalum, ceramic, etc), bioactive materials (bioglass,
hydroxylapatite, etc.) and reabsorbable biomaterials (polylactic acid,
polyglycolic polymers and processed bone grafts etc) [5]. However,
biotolerant materials are still the most widely used in clinic at present,
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attributing to their excellent mechanical properties and biocompatibility.
However, An ideal artificial bone implants for long-term use should
possess not only favorable mechanical properties and biocompatibility,
but high resistance to corrosion and friction [6, 7]. Metallic biomaterials
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such as titanium are the most used artificial bone implants in clinic [8, 9].
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However, debris generating from frequent friction are almost inevitable
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after long-term usage (around 10 years) of metallic implants. The
accumulation of these debris can easily lead to aseptic inflammation and
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implant-associated osteolysis, resulting in prosthesis-loosening which can
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only be solved through artificial joint revision surgery [10-12].
Theoretically, pure ceramic biomaterials possess a significant high
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abrasion resistance. They should be more desirable for long-term uses of
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various implants, especially for joint replacement implants. This have
confirmed by many literatures and clinical results in recent years [13-15].
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However, ceramic biomaterials have their intrinsic defective property of
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fragility, hampered their clinical application [16, 17]. Besides, since most
of ceramic biomaterials are difficult to be implanted through minimally
invasive surgery, the risk of post-operative infection also cannot be
ignored [18]. Significantly improved mechanical properties and broad
spectrum antibacterial capacity are still the challenges for ceramic
implant as an ideal implants.
Bioinspired from the structure of nature rose, a dual layered
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modified ceramic implant was constructed to overcome above drawbacks
of fully ceramic implants in present study. A superplastic layer of ISO
resin was modified on the surface of ceramic implants to enhance its
mechanical properties, and a nano-zinc oxide (ZnO) slices as the second
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layer were surface modified to prevent the implants from bacterial
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invasion. Microstructure and mechanical properties of the dual layered
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modified ceramic implant were performed. Moreover, in vitro and in vivo
Biocompatibility and antibacterial properties were investigated.
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2. Experimental Section
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2.1. Fabrication of ZnO-I&R dual layered modified ceramics.
Yttrium oxide-stabilized zirconium oxide (3Y-ZrO2) nano-powder
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was used to prepare two different shapes of ceramics by gel-casting
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method. Briefly, an aqueous mixture of 3Y-ZrO2 nano-powder and
ammonium citrate was prepared and pH was adjusted to 9 with ammonia.
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Then acrylamide, N,N'-methylene bisacrylamide, ammonium persulfate
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and tetramethylethylenediamine were added. The ceramic slurry was
slowly poured into 3D-printed molds which were realized by 3D software
CATIA and 3D printer (Makerbot Z18, America), followed with gelation
and drying at temperature of 55 ℃ for two days in vacuum. The obtained
green bodies were sintered at 1200 ℃ forming 3Y-ZrO2 ceramics. Then
ISO resin were uniformly coated on the ceramics by a thermal spray
coating process under pressure of 2000 psi and temperature of 65 ℃, with
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the thickness of the ISO resin layer was controlled at about 1mm.
Nano-zinc oxide solution was synthesized by adding 50 mM Zn(NO3)2﹒
6H2O, 80 mM NH3﹒H2O and 25 mM hexamine into 400mL deionized
water, followed by 85 ℃ water bath for 24 h. Then the nano-zinc oxide
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solution was dropped on ISO resin coated ceramics, forming the ZnO-
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ISO dual layered modified ceramics [19].
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2.2. Characterization
The crystalline patterns of ZrO2 nano-powder sintered at different
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temperatures (600 ℃, 800 ℃, 1000 ℃ and 1200 ℃, respectively) were
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analyzed by X-ray diffraction (Rigaku D/max 2550 , Japan). Then
DSC-TG analysis of ZrO2 ranging from 30 ℃ to 1300 ℃ was recorded
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using thermogravimetry (Netzsch STA, Germany). The morphology of
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unmodified ceramic, ISO resin coated ceramic and ZnO- ISO dual
layered modified ceramic were examined by scanning electron
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microscope (SEM) (Zeiss, Germany). And the nano-zinc oxide was
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analyzed by transmission electron microscopy (TEM) (Zeiss, Germany).
Mechanical properties of samples in bending test, tensile test and
compressive test were evaluated by a WDW series electronic universal
testing machine (Hualong, China). Impact mechanical property was
performed on a CBD series auto controlled impact testing machine
(Hualong, China) to accomplish the impact test.
2.3. Antibacterial Properties Assay in vitro
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Antibacterial properties of ISO resin coated ceramic and ZnO- ISO
dual layered modified ceramic were analyzed. Unmodified ceramics were
set as control group. All samples were sterilized by ethylene oxide before
test. This study was processed against two of the most common clinical
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strains: Staphylococcus aureus (S.aureus, gram positive, ATCC 25923)
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and Escherichia coli (E.Coli, gram negative, ATCC 25922). Five
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milliliters of Luria−Bertani broth, 100 μl of bacterium suspension and
sample were mixed in sterile tube and cocultured in an orbital shaker for
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24 h. After that, 100 μl of the coculture solution was taken out and diluted
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105 times. Then 50 μl of the media was used to coat on Petri dish which
was placed in a constant temperature incubator (37 °C) for 24 h. Plate
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samples [20].
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counting method was used to compare antibacterial potency of different
2.4. Cytotoxicity Assay
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Cytotoxicity of ISO resin was analyzed by cell counting kit-8
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(CCK-8) assay. Briefly, sterile ISO resin coated ceramic was soaked into
cell culture medium as a ratio of 1cm2 material to 1mL cell culture
medium according to the standard procedures in ISO10993. The mixture
was incubated in a cell culture incubator containing 5% CO2 at 37 ℃.
After 24 h, the solution was collected as extract concentrate and diluted
by the cell culture medium to ratios of 1/2, 1/4, 1/8, 1/16. Then rat bone
marrow mesenchymal stem cells (rBMMSCs) were seeded in 96-well
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plate at an initial density of 5×103 cells/well and cultured in different
concentrations of the extracts. The extracts were changed in every two
days. The cell culture medium without extract addition was used as blank
group. rBMMSCs were continuously cultured for 7 d and CCK-8 assay
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was applied to detect cell OD values at time point of 1, 3 and 7 d
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respectively according to manufacturer's instructions. Enzyme-linked
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immunosorbent assay microplate reader (Synergy 2, Bio-TEK) was used
to measure OD value of each well at a wavelength of 450 nm which
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reflected the number of alive cells [21].
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2.5. In Vivo Biocompatibility Studies
The toxicity of ISO resin was conducted by directly contacting with
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mouse tissue (24 h toxicity test) and tail vein injecting of ISO resin
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extract solution with PBS (14 d toxicity test). All animal use procedures
were according to the NIH guide for the Care and Use of Laboratory
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Animals and were approved by the local Care Committee.
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24 h toxicity test: All surgeries were performed under aseptic
conditions, with sterile surgical instruments and operating table. After 8 h
fasting period, the mice were given anesthesia intraperitoneally with 3%
pentobarbital sodium solution (Sigma) at a dosage of 1.0 mL/kg [22]. A
full thickness incision (length = 1.0 cm) was created from the dorsum on
each mouse. Sterile ISO resin (10 mm × 10 mm × 2.5 mm) was placed
subcutaneously, directly contacting with skin and muscle in experimental
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group while the control group was taken operation only. After 24 h, all
mice were sacrificed by cervical dislocation. The tissues of surgical site
were removed for further histological analysis (hematoxylin and eosin
staining, H&E staining). The specimens dehydrated with a graded series
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of ethanol were embedded in paraffin and sectioned (approximately 5 m
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thickness), stained with hematoxylin and eosin, then analyzed under a
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light microscope [23, 24].
14 d toxicity test [25]: Sterile ISO resin was soaked into fresh
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phosphate buffered solution (PBS) as the proportion of 1 cm2/mL for 24 h.
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The extract (0.1 mL) was directly injected into experimental group mice
by caudal vein injection once a day, lasting for 14 d while the control
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group were injected with PBS (0.1 mL) only. The mice were carefully fed
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for 14 d, afterwards, all mice were anesthetized with ether. Blood samples
obtained by cardiac puncture were collected for biochemical test. Then
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the mice were sacrificed by cervical dislocation and immediately
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eviscerated. The hearts, livers, spleens, lungs and kidneys removed from
the mice were fixed in 10 % neutral buffered formalin for further
histological analysis (H-E staining). Blood samples were immediately
sent to be done biochemical analyses.
3. Results and Discussion
3.1 Preparation of ZnO- ISO dual layer modified ceramic
In order to improve the mechanical and antibacterial properties of
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ceramic implants, a ZnO- ISO dual layer modified ceramic implant was
constructed bioinspired from the structure of nature rose. As depicted in
Figure 1A, some relative slender parts which are similar with the inner
parts of rose stem are easy to be damaged (As shown Figure 1B). While
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this brittle area of rose was protected by a dual layered coverage: rose
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cortex and rose thorn. The rose cortex can remarkably improve the
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physical strength of the stem, and the thorns can effectively protect the
rose from biological attacks. Based on this inspiration, a similar dual
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layered modification was constructed for slender ceramic rod (Figure 1C):
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the most fragile area of ceramic was firstly coated with a plastic layer of
ISO resin to enhance mechanical properties of ceramic implants. Then
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nano-zinc oxide (ZnO) slices were surface modified, as the second layer,
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preventing the implants from bacterial invasion.
Figure 1. Schematic of a dual layered modification of ceramic
scaffolds. (A) Integrative ceramic biomaterial has many advantages, but
some slender parts of it are too fragile, limited its further use. (B) The
idea of the proposed dual layered modified ceramic was inspired from
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rose. Cortex and thorns, the dual layered structure of rose, protected inner
rose stem. (C) Due to the rose inspiration, dual layered modified ceramic
was constructed. The first layer was ISO Resin, organic coating on
ceramic. Then nano-ZnO slices as the second layer covered on the surface
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of ISO modified ceramic.
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Zirconia ceramics are biocompatible and have been shown to have
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higher fracture toughness and bending strength than other ceramics,
making them suitable as materials for bone implants or dental implants.
good clinical outcomes
[26]. Hence, we chose yttrium
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with
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They have extensively been used as ball heads in total hip replacements
oxide-stabilized zirconium oxide (3Y-ZrO2) ceramics as the ceramic
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implants for dual layered modification. 3Y-ZrO2 ceramics with different
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shapes were fabricated by gel-casting method, and then sintered at
different temperature. To ensure the stability of this ceramic biomaterial,
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DSC-TG analysis (Figure S1A) was used to study its changes at different
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heating stages (ranging from 0 ℃ to 1300 ℃). As a result, no significant
variation on the TG value of ZrO2 was observed during the entire heating
process. On the other hand, the volatilization of organic components and
water led TG value falling down from 100 % to 97.95 % which illustrated
ZrO2 involved in this experiment was stable. There was a peak within the
range of 300-400 ℃, indicating crystal transformation of ZrO2 occurred.
Afterward, different ZrO2 samples sintered at 600 ℃, 800 ℃, 1000 ℃ and
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1200 ℃ were then analyzed through XRD respectively (Figure S1B).
Results revealed the uniform and well crystal growth of ZrO2. No extra
crystalline phase was found. Therefore, the sintering temperature of 1200 ℃
was selected for ZrO2 samples preparation.
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3D printed technique was employed to construct appropriate shaped
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slot molds (Figure 2A), and then uniform columnar and rod-like ceramics
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were accordingly fabricated by gel-casting process (Figure 2B) for
mechanical tests. Figure 2B and Figure 2C indicated all ceramics had
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smooth appearance. Then ISO resin layers were modified on the surfaces
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of two different shaped ceramics (Figure 2D and Figure 2E), respectively.
It is worthy to note that ISO resin material possessed high quality, certain
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elasticity and smooth surface without peculiar smell. The thickness of
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subsequent tests.
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ISO resin material on ceramics was set as approximately 1mm for the
Figure 2. Different optical images show that the fabricated samples
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were uniform. (A) 3D-printed long slot molds. (B) Rod-shaped ceramics.
(C) Columnar ceramic. (D) Rod-shaped ceramics sprayed with ISO resin
layer. The coating thickness was adjusted to approximate 1mm. (E)
Columnar ceramics sprayed with ISO resin layer.
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The relative mechanical properties on 3Y-ZrO2 ceramics and ISO
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resin modified ceramics were summarized in Figure 3. Four different
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groups of the tests were carried out, including impact test (Figure 3A),
bending test (Figure 3B), tensile test (Figure 3C) and compressive test
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(Figure 3D). Impact test showed that, after merely 1mm modification,
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ISO resin modified ceramics (1.47±0.11 J) could withstand two times
more impact force than the unmodified ceramics (0.62±0.09 J) (Figure
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3A). In bending test, the ISO resin modified ceramics (23.72±9.01 N) had
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three times higher bending force resistance than unmodified ceramics
(7.10±2.48 N) (Figure 3B and Figure S2). Tensile test also revealed the
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ISO resin modified ceramics (18.03±0.76 Mpa) had more anti-tensile
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capacity than unmodified ceramics (11.56±1.70 Mpa) (Figure 3C and
Figure S2). Another straightforward demonstration was provided in the
form of an interesting video section: both unmodified ceramic and ISO
resin modified ceramic were dropped from hands of a robot
simultaneously. The control group shattered into different pieces of
various shapes while the experimental group was undamaged (The video
segment was provided in the supplementary information). Above results
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proved that the mechanical properties of ISO resin modified ceramics
were significant enhanced. It was worth noting that in impact test, the
unmodified ceramics had (Figure 3F, f) not only exhibited worse
mechanical properties, but also showed sharply irregular fracture section.
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As a comparison, the fracture section of experimental group (Figure 3E, e)
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was smooth and regular. This phenomenon was also shown in bending
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test and tensile test. This phenomenon is main caused by the superplastic
properties of ISO resin layer. Owning to the intrinsic fragility of ceramics,
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they tend to be broken instantly and show a sharp fracture section when
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subject to impact force. After the modification of superplastic ISO resin,
the impact force can be absorbed by ISO resin layer quickly and then then
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gradually released on the ceramics, resulting a smooth fracture section
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and higher force resistance of ISO resin modified ceramics. Considering
ceramic artificial joint might be fractured by some serious accidents,
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there is a potential risk to take difficult revision surgery in clinic when
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several small sized pieces of implant were remained in the surrounding
tissue. ISO resin material modified ceramics with improved mechanical
properties and regular fracture section could be a better alternative.
Another interesting phenomenon was observed in compressive test.
Although, there was no significant difference between two groups in
compressive test (Figure 3D). The main reason might be ISO resin
material couldn’t provide supportive force. But the ceramics in control
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group (Figure 3H) were instantly fractured leading numerous ceramic
pieces. If this process occurred in human, the tissues surrounding
ceramics would be damaged severely. On the other hand, the inner
ceramics in experimental group (Figure 3G) were also completely
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compressed into pieces, but the outer ISO resin layer kept the integrity of
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the ceramic shapes and ceramic pieces were not harmful to the
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surroundings.
Figure 3. Mechanical tests. (A-D) Four kinds of mechanical tests were
implemented: impact test (p***<0.001), bending test (p*<0.05), tensile
test (p***<0.001) and compressive test (p>0.05). (E-F) Cross sections of
the ceramics after impact test. (e-f) The inserts images are the high
magnification of the red circle selected area. The purple arrows in inserts
image (f) point to irregular cross section in control group. (G-H) Optical
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images of different group ceramics after compressive test.
3.2 Antibacterial properties of dual layered modified ceramic
In order to endow ceramic implants with antibacterial properties,
nano-ZnO surface modification was further preformed. Figure 4A-C
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showed the SEM morphology of unmodified ceramic, I&R material
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coated ceramic and ZnO- ISO dual layered modified ceramic respectively.
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It is demonstrated that the ceramic was well coated by ISO resin and the
nano-ZnO slices were evenly distributed on the surface of ISO resin
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coated ceramic. TEM image of the nano-ZnO slices (Figure 4D) showed
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the average size of as-synthesized nano-ZnO slices was about 100nm.
Wafers were selected as the model substrates to quantitatively investigate
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the antibacterial performance of ISO resin modified ceramics and
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ZnO-ISO dual layered modified ceramic, and unmodified ceramic was set
as control group. ISO resin shows no inhibition on the growth of both
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S.aureus (gram positive bacteria) and E.Coli (gram negative bacteria) at
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all (Figure 4E, F and S3). No obvious different was found on the numbers
of bacterial colonies between ISO resin modified ceramic and unmodified
ceramic. In contrast, ZnO-ISO dual layer modified ceramic exhibited
excellent antibacterial activities against both S.aureus and E.Coli (Figure
4G, H and S3). Almost no bacterial colonies formed when bacteria were
treated with ZnO-ISO dual layered modified ceramic.
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Figure 4. Morphology of modified ceramics and antibacterial
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properties assay in vitro. SEM images of unmodified ceramic (A), ISO
resin modified ceramic (B) and ZnO-ISO dual layered modified ceramic
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(C). The images were processed by pseudo color, and each color
represented different composition: yellow (ceramic), green (ISO resin),
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red (ZnO nanoslices). (D) TEM image of ZnO nanoslices. (E-H)
Antibacterial studies of different ceramic coatings against E.coli and
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S.aureus in vitro, for ISO resin modified ceramic (p>0.05) and ZnO-ISO
dual layered modified ceramic (p***<0.001).
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3.3 Biocompatibility Studies of dual layered modified ceramic
Since ceramic is known to have well biocompatibility and zinc oxide
is the only nano-sized antibacterial material certified by the FDA in vivo
[27, 28], the present cytotoxicity study was mainly focused on the
biocompatibility of ISO resin layer. Cytotoxicity test (CCK-8) revealed
the rat bone marrow mesenchymal stem cells could be suppressed only
under 7 days’ continuous culture in high concentrations of extracts (50%
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and 100%), while other conditions no obvious influence on cell growth
was found (Figure 5A). But such extreme condition would not occur in
human body as normal metabolism of body fluid existed. 24 h toxicity
test of ISO resin to mice was further studied in vivo (Figure 5B-D).
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Results showed that, after contacting with ISO resin for 24 h, there was
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no macroscopic abnormalities such as swelling, hemorrhage, necrosis in
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skin or muscle (Figure 5D).
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Figure 5. Cytotoxicity assay and 24 h toxicity test. (A) Cytotoxicity of
ISO resin material was analyzed by CCK-8 assay. (B-D) The optical
diagram of mice in 24 h toxicity test. (E-H) The tissues (skin and muscle)
around the ISO resin implant materials were stained by H&E method in
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24 h toxicity test.
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Furthermore, skin and muscle of mice were sliced and stained by
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H&E for pathological examination. Results in Figure 5E-H further
revealed that there was no noticeable tissue abnormality. Additionally, as
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showed in Figure 6, within 14 days’ continuous observation, mice of both
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experimental group and control group showed normal daily activities and
diets. There was no significant difference in H&E histologic analysis of
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major organs (heart, liver, spleen, lung and kidney) (Figure 6 A-J) and
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blood tests (TBIL, ALT, AST, ALP, UREA and CREA) (Figure 6 K-P).
All the results proved that ISO resin material had excellent
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biocompatibility for contacting tissues and important organs, without
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influencing morphology and function of them.
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Figure 6. 14 d toxicity test. (A-J) The mice organs (heart, liver, spleen,
lung and kidney) were stained by H&E method in 14 d toxicity test. (K-P)
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Biochemical analyses (TBIL, ALP, CREA, UREA, ALT, AST) of mice
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blood samples were shown in 14 d toxicity test
4. Conclusions
Infection is still a critical problem affecting the therapeutic effects of
ceramic implants. Meanwhile, fragility is a key problem for the wide use
of ceramics. Aiming to overcome these two disadvantages, we inspired
from natural rose and developed ZnO-ISO dual layered modification on
3Y-ZrO2 ceramics implants. Further experimental results demonstrated
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that, the proposed dual layered modification could not only enhance
mechanical properties, but also endow antibacterial ability. Considering
the great biocompatibility of this dual layered modification, we believe
the current study could promote the revival of several ceramic based
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biomaterials. However, the long-term effects of ZnO-ISO dual layered
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modified ceramic implant in the body, are still unknown. More systematic
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in vivo study of ZnO-ISO dual layered modified ceramic is needed before
further clinical application.
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Acknowledgments
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This work was supported by the National Natural Science Foundation of
China (No.21461015 to Wang Xiaolei); the Science Foundation of
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Jiangxi Provincial Department of Education (No.KJLD14010 and
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20153BCB23035 to Wang Xiaolei); the major program of Natural
Science Foundation of Jiangxi Province (No.20161ACB21002 to Wang
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Xiaolei); the Foundation of Health and Family Planning Commission of
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Jiangxi Province (No. 20155246 to Li Chen); the Science Foundation
Jiangxi Provincial Department of Traditional Chinese Medicine (No.
2013A243 to Li Chen); the Foundation of The Second Affiliated Hospital
of Nanchang University (No. 2016YNZJ12007 to Li Chen); China
Postdoctoral Science Foundation (No. 2017M610402 to Ai Fanrong);
Postdoctoral Science Foundation of Jiangxi Province (No. 2017KY06 to
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Ai Fanrong); LINE-X(CHINA) Company is appreciated for the technical
support for ISO resin surface modification.
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Author Contributions
X.L.W. conceived and designed the experiments. C.L. and F.R.A.
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performed the sample fabrication involved in this experiment,
characterization, cytotoxicity assay and data analysis and wrote the
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manuscript. X.X.M. and H.L. accomplished the mechanical tests. F.S.L.
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and M.Z.L. accomplished the antibacterial properties assay in vitro. F.Y.
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and L.N.D. contributed to biocompatibility studies in vivo. T.L. revised
the paper. X.L.W. is corresponding author. All authors discussed the
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results and commented on the manuscript.
Additional information
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Supplementary information accompanies this paper.
Conflict of interest: The authors declare no conflicts of interest for this
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article.
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Graphical Abstract
Inspiration of the dual layered modification of ceramic scaffolds from
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natural rose
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Highlights:
Inspired from natural rose, a dual-layer-modified ceramic scaffold was
constructed by coating isocyanate resin and nano Zinc Oxide layers on the ceramic
scaffold.
The proposed dual-layer-modification significantly improved their mechanical
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properties and their broad spectrum antibacterial capacity.
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