International Orthopaedics

https://doi.org/10.1007/s00264-020-04584-z

ORIGINAL PAPER

Effects of umbilical cord mesenchymal stem cells loaded

with graphene oxide granular lubrication on cytokine levels in animal
models of knee osteoarthritis
Xiao-dong Wang 1 & Xiao-chun Wan 1 & Ai-feng Liu 2 & Rong Li 3 & Qiang Wei 4

Received: 31 January 2020 / Accepted: 27 April 2020

# SICOT aisbl 2020

Abstract
Background The aim of this study was to use umbilical cord mesenchymal stem cells (UCMSCs) loaded with graphene oxide
(GO) granular lubricant to treat knee osteoarthritis (KOA) animal models and to analyze their effect on cytokine levels in the
articular cavity.
Methods Twenty-four New Zealand rabbit models of KOA were established by the modified Hulth and cartilage injury method,
and they were assigned to the blank group, the GO group, the UCMSC group, and the GO + UCMSC group, each group
containing six animal models. The GO and UCMSC groups were treated by a single intra-articular injection. The treatment was
started one month after surgical modeling, and the observation period was eight weeks. The expression levels of nitric oxide
(NO), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), glycosaminoglycan (GAG), and collagen-II (COL-II) in serum
and articular fluid after treatment were compared to analyze the efficacy.
Results The GO granular lubricant caused no significant improvement in the intra-articular environment of the knee joint, and
UCMSCs caused a certain degree of improvement in the inflammatory environment. The improvement results of NO, IL-6,
TNF-α, GAG, and COL-II were the best in the GO + UCMSC group, but the improvement results of inflammatory cytokine
levels in serum and articular fluid were not consistent, especially the differences in NO, IL-6, and TNF-α were greater.
Conclusion UCMSCs loaded with the GO granular lubricant can reduce the inflammatory level and improve the level of
biochemical environment in the articular cavity, and thus promote cartilage repair.

Keywords Knee osteoarthritis . Graphite oxide . Umbilical cord mesenchymal stem cell . Cartilage . Cytokine

Introduction achieved, none of these methods can restore the previous

Knee osteoarthritis (KOA) is a common chronic joint disease,
and middle-aged and old people are the most commonly af-
fected group [1]. Although there are many clinical treatment
methods for this disease and some curative effects have been
* Ai-feng Liu
312223648@qq.com
1
Department of Rehabilitation Medicine, Tianjin Medical University
General Hospital, Tianjin, China
2
Orthopaedics Department, First Teaching Hospital of Tianjin
University of Traditional Chinese Medicine, Tianjin 300193, China
3
Boya Stem Cell Technology Co., Ltd., Beijing, China
4
Materials Science and Engineering Department, Hebei University of
Technology, Tianjin, China
function of the joint very well. This is because it is difficult
to repair the articular cartilage after being damaged. It lacks a
vascular structure and is not conducive to cartilage regenera-
tion. Even if the structure is repaired, it is difficult to restore
the biomechanical and biochemical functions of the cartilage
[2, 3].
However, in recent years, the development of tissue engi-
neering has provided a new way to solve this problem. The
application of mesenchymal stem cells (MSCs) had always
been the focus in this field. Graphite oxide (GO), a new ma-
terial for tissue engineering, is gradually emerging in the med-
ical field. GO as a scaffold carries MSCs as seed cells, which
may inspire a new idea and a brand-new treatment method for
the treatment of KOA.
Umbilical cord mesenchymal stem cells (UCMSCs) are a
rich source of obtaining and more primitive. There is no ad-
verse effect on the mother and fetus when these cells are

collected. They can be easily separated, and they have good
amplification ability and immune regulation ability.
Meanwhile, they can express some embryonic markers [4].
Research shows that UCMSCs have the potential to differen-
tiate into cartilage, improve the microenvironment of osteoar-
thritis, and promote cartilage regeneration by secreting a vari-
ety of cytokines [5–11].
GO can be prepared as a reticular three-dimensional struc-
ture, and this structure is obviously superior to the two-
dimensional structure in MSC culture [12]. Moreover, it has
the electrostatic adsorption effect, which can aggregate cells
well or locate them in the damaged area. In addition, GO itself
has the ability to promote the proliferation and differentiation
of MSCs.
The influence on the environment can cause the linkage
reaction of chondrocytes themselves, so as to achieve the pur-
pose of cartilage repair. The knee joint-cartilage-cartilage ex-
ternal environment is regarded as an organic whole rather than
a separate structure [13]. Although the MSCs are a hot topic in
research, there are few studies on their combined scaffold
materials [14]. At present, there is no report on the combina-
tion of GO and MSCs in a living animal model for three-
dimensional culture. The application of this combination in
the treatment of KOA to observe its effect on cytokine levels
in the model has never been studied.
Therefore, 24 New Zealand rabbits were selected for this
study. Method of using modified Hulth and cartilage injury
induced animal models of KOA and applied UCMSC loaded
with GO granular lubrication in the treatment and revealed its
effect on cytokine levels.
Methods
Experimental equipment
UCMSCs were purchased from Beijing Boya Stem Cell
Technology Co., Ltd. The following selected reagents and
drugs were obtained from the animal experimental centre of
Tianjin University of Traditional Chinese Medicine and
Tianjin Institute of Orthopaedics integrated with Chinese
and Western Medicine: nitric oxide (NO) kits (USA,
Cranford, CCC company), IL-6 kits (USA, Cranford, CCC
company), TNF-α kits (USA, Cranford, CCC company),
GAG kits (USA, Cranford, CCC company), COL-II kits
(USA, Cranford, CCC company); micro-CT (Germany,
Siemens Company), centrifuge (USA, Thermo Fisher
Scientific Company), and Microplate Reader (USA, Thermo
Fisher Scientific).
A total of 24 animals were selected for the experiment. The
animals were 12-week male New Zealand white rabbits pro-
vided by the animal experimental center of Tianjin University
of Traditional Chinese Medicine (Tianjin, scxk-JIN 2016-
International Orthopaedics (SICOT)
0001), with a body mass of about two kg and a clean level
cultured environment [15–17].
UCMSC cultured
The UCMSC used in the experiment was from Boya Stem
Cell Technology Co., Ltd. It was isolated, cultured, and tested
in its laboratory. To select UCMSC from generation P0 to P7,
when the cell fusion rate reached 70–80%, the living morphol-
ogy of USMSC was directly observed under an inverted mi-
croscope and photographed. The tested standard is based on
the MSC definition standard recommended by the
International Society for Cellular Therapy (ISCT) in 2006
[18] (Fig. 1).
GO granular lubrication
GO granules were mixed into sodium hyaluronic acid (HA)
injection separately for ultraviolet sterilization. Then, GO and
HA were mixed, and the syringe containing the mixture was
repacked into the original packaging and sealed with a sealing
film (Fig. 2).
The preliminary experiment of this study confirmed that
the GO granular lubrication had a repairing effect on the
KOA model established by rats [19]. The GO granular lubri-
cation demonstrated an apparent antifriction effect on the joint
surface, providing a stable environment for cartilage repair.
The adjustment of microenvironment between the cartilage
friction interfaces might contribute to the treatment of osteo-
arthritis through ecological restoration. In addition, the exper-
iment also confirmed the GO granular lubrication has good
biosafety.
Modified Hulth and cartilage injury model
According to the review of the animal experiment center of
Tianjin University of Traditional Chinese Medicine, the ani-
mal experiment scheme and related materials involved in the
project meet the ethical requirements of experimental animal
welfare and animal experiment. This was a surgical method
modeling, and the specific steps were as follows [20]: The
animal was induced by inhalation of 5% ether followed by
intramuscular injection of a combination of xylazine
five mg/kg and ketamine 35 mg/kg. All surgical procedures
were performed with all efforts to minimize suffering. The
skin over the right knee joint was prepared and disinfected
after anesthesia. The animal was placed on the operating table,
and the limbs were fixed. Under aseptic conditions, a medial
longitudinal incision of about two cm in length was made on
the right knee joint. The cavity of the knee joint was exposed
layer by layer. Then, the anterior cruciate ligament was
resected, the medial meniscus was resected, and the model
of joint instability was created (Fig. 3). After the operation,
International Orthopaedics (SICOT)

Fig. 1 UCMSC surface marker detection

each model was administered one ml of four U gentamicin for
three days to prevent infection. Animals were free to move
and eat, and their injured limbs were not fixed.
Detection of the KOA model
following three groups: GO granule lubrication treat-
ment group (GO group), UCMSC treatment group
(UCMSC group), and the UCMSCs loaded with GO
granule lubrication (GO + UCMSC group). Each group
consisted of six rabbits and 18 rabbits in total.

After establishment of the KOA animal model, observa-

tion was conducted for four weeks, including survival
and activity. After the observation, the experimental rab-
bits were killed by ear vein air embolization. Then, the
right knee joint cavity was opened and resected, and the
redundant muscle and ligament were removed by an
aseptic operation. The changes in the cartilage and
synovium were observed and recorded.
Using the preclinical small animal PET/SPECT/CT sys-
tem, a micro-CT scan was performed on the right knee spec-
imens of the animal model with a thickness of 80 μm. The
injury to the articular cartilage and subchondral bone was
evaluated (Fig. 4).

Experimental grouping

There were a total of 24 animal models, without any animal

death, and the modeling process was successful. The
animal models were divided into a blank control group
of six rabbits and a treatment experimental group of 18
rabbits. According to the different treatment methods,
the experimental group was further divided into the
Fig. 2 GO solid particle lubricant
 International Orthopaedics (SICOT)

Fig. 3 Establishment of
improvement Hulth + cartilage
injury mode

Therapeutic method
The concentrations of GO granular lubrication and
UCMSCs were selected by referring to the previous
research and relevant literature conclusions [6, 19,
21–24] (Figs. 5 and 6).
cytokines, such as NO, GAG, and COL-II in serum and artic-
ular fluid, was determined by ELISA [25].
Micro-CT was used to scan the animal model specimens of
each group after treatment, the thickness of the section was
80 μm, and evaluate the damage of articular cartilage and
subchondral bone.

a. In the GO group, 0.5 ml of the GO granule lubrication was Statistical methods

injected into the right knee cavity of the animal model
with a one ml syringe at a concentration of 30 μg/ml SPSS19.0 software was used for statistical analysis. The mea-
GO + 0.25% HA. surement data were expressed as x ± s and compared by the t
b. In the UCMSC group, 0.5 ml of the UCMSCs was test. Results before and after treatment were compared by an
injected into the lumen of the right knee of the animal ANOVA, α = 0.05.
model with a one ml syringe at a concentration of five ×
106 cells/ml.
c. In the GO + UCMSC group, 0.5 ml of the UCMSCs
loaded with GO granule lubrication was injected into the
right knee joint cavity of the animal model. The concen-
tration of GO granule lubrication was 30 μg/ml GO +
0.25% HA, and the concentration of UCMSCs was five ×
106 cells/ml.

Observation index

Four weeks after the model was established, treatment was

initiated, during which there was no restriction of water supply
and free movement.
After eight weeks of treatment, five ml of venous blood
was extracted from the KOA animal model under aseptic con-
ditions and injected into a heparinized centrifuge tube. The
serum was centrifuged at 3000 r/minutes for ten minutes for
collection, and it was stored at − 20 °C. Meanwhile, 0.5 ml of
the articular fluid was extracted from the knee joint cavity of
the KOA animal model (normal saline was injected into the
right knee cavity with a one ml syringe and extracted to collect
the articular fluid), and centrifuged at 5000 r/minutes for ten
minutes. Then, 150 μl of the supernatant was taken from the
pipper and stored at − 20 °C as standby. The content of Fig. 4 Surgical model
International Orthopaedics (SICOT)

Fig. 5 American Blood Bank Association AABB Certification

Results The difference between the GO + UCMSC group and the

NO results
The NO serum results of the model are as follows: 22.097 ±
0.352 ng/ml in the blank group, 21.436 ± 0.031 ng/ml in the
GO group, 21.020 ± 0.026 ng/ml in the UCMSC group, and
17.624 ± 0.127 ng/ml in the GO + UCMSC group.
blank group was highly statistically significant (P < 0.01). The
differences among the GO group, UCMSC group, and blank
group were not statistically significant (P > 0.05). The differ-
ence between the GO + UCMSC group and the UCMSC
group was not statistically significant (P > 0.05).
The NO articular fluid results of the model were as follows:
27.667 ± 0.485 ng/ml in the blank group, 26.627 ±
0.339 ng/ml in the GO group, 25.981 ± 0.305 ng/ml in the
UCMSC group, and 21.733 ± 0.135 ng/ml in the GO +
UCMSC group.
The differences between the GO + UCMSC group and
blank group and the UCMSC group were highly statistically
significant (P < 0.01). The difference between the UCMSC
group and the blank group was statistically significant
(P < 0.05). The difference between the GO group and the
blank group was not statistically significant (P > 0.05).
The differences between the results of NO in serum and
articular fluid were statistically significant in each group
(P < 0.05; Table 1).

Table 1 Serum and articular fluid NO results after treatment (x ± s,

ng/ml)

Group Serum Articular fluid P

Blank group 22.097 ± 0.352 27.667 ± 0.485 0.000

GO group 21.436 ± 0.0311 26.627 ± 0.3394 0.007
UCMSC group 21.020 ± 0.0262 25.981 ± 0.3055 0.006
GO + UCMSC group 17.624 ± 0.1273 21.733 ± 0.1356 0.042
1–6
Compared with the blank group, P values were 0.192, 0.064, and
Fig. 6 Fifteen micrograms per milliliter of GO particle lubricant 0.008; 0.130, 0.038, and 0.001, respectively
 International Orthopaedics (SICOT)

Table 2 Serum and articular fluid IL-6 results after treatment (x ± s, Table 4 Serum and articular fluid COL-II results after treatment (x ± s,
ng/ml) ng/ml)

Group Serum Articular fluid P Group Serum Articular fluid P

Blank group 16.082 ± 0.323 10.303 ± 0.240 0.000 Blank group 13.475 ± 0.342 8.308 ± 0.133 0.000
GO group 10.957 ± 0.3431 9.327 ± 0.2544 0.028 GO group 14.127 ± 0.1021 9.391 ± 0.3504 0.030
UCMSC group 9.668 ± 0.1942 7.377 ± 0.3455 0.013 UCMSC group 15.589 ± 0.0632 11.652 ± 0.7015 0.109
GO + UCMSC group 7.426 ± 0.2943 4.034 ± 0.4266 0.015 GO + UCMSC group 19.372 ± 0.0633 14.127 ± 0.1026 0.001
1–6
Compared with the blank group, P values were 0.000, 0.000, and 1–6
Compared with the blank group, P values were 0.123, 0.005, and
0.000; 0.088, 0.025, and 0.000, respectively 0.000; 0.101, 0.042, and 0.000, respectively

IL-6 results TNF-α results

The IL-6 serum results of the model are as follows: 16.082 ±
0.323 ng/ml in the blank group, 10.957 ± 0.343 ng/ml in the
GO group, 9.668 ± 0.194 ng/ml in the UCMSC group, 7.426
± 0.294 ng/ml in the GO + UCMSC group.
The differences among the GO + UCMSC group, the
UCMSC group, the GO group, and the blank group were
highly statistically significant (P < 0.01).The difference be-
tween the GO + UCMSC group and the UCMSC group was
highly statistically significant (P < 0.01).
The IL-6 articular fluid results of the model are as follows:
10.303 ± 0.240 ng/ml in the blank group, 9.327 ± 0.254 ng/ml
in the GO group, 7.377 ± 0.345 ng/ml in the UCMSC group,
4.034 ± 0.426 ng/ml in the GO + UCMSC group.
The differences among the GO + UCMSC group and blank
group and the UCMSC group were highly statistically signif-
icant (P < 0.01). The difference between the UCMSC group
and the blank group was statistically significant (P < 0.05).
The difference between the GO group and the group was not
statistically significant (P > 0.05).
The difference between the results of IL-6 in serum and
articular fluid was as follows: The difference was highly sta-
tistically significant in the blank group (P < 0.01). The differ-
ences were statistically significant in the GO group, the
UCMSC group, and the GO + UCMSC group (P < 0.05;
Table 2).
The TNF-α serum results of the model are as follows: 9.466 ±
0.177 ng/ml in the blank group, 8.447 ± 0.113 ng/ml in the
GO group, 6.109 ± 0.044 ng/ml in the MSC group, 5.139 ±
0.183 ng/ml in the GO + MSC group.
The differences among the GO + UCMSC group, UCMSC
group, GO group, and blank group were highly statistically
significant (P < 0.01). The difference between the GO +
UCMSC group and the UCMSC group was highly statistical-
ly significant (P < 0.01).
The TNF-α articular fluid results of the model were
as follows: 11.627 ± 0.104 ng/ml in the blank group,
10.897 ± 0.124 ng/ml in the GO group, 8.462 ±
0.095 ng/ml in the MSC group, 5.401 ± 0.086 ng/ml in
the GO + UCMSC group.
The differences among the GO + UCMSC group and blank
group and the UCMSC group were highly statistically signif-
icant (P < 0.01). The difference between the UCMSC group
and the blank group was statistically significant (P < 0.05).
The difference between the GO group and the blank group
was not statistically significant (P > 0.05).
The difference between the results of TNF-α in serum and
articular fluid was as follows: The difference was highly sta-
tistically significant in blank group (P < 0.01).The differences
were statistically significant in the GO group, the UCMSC
group, and the GO + UCMSC group (P < 0.05; Table 3).

Table 3 Serum and articular fluid TNF-α results after treatment (x ± s, Table 5 Serum and synovial fluid GAG results after treatment (x ± s,
ng/ml) ng/ml)

Group Serum Articular fluid P Group Serum Articular fluid P

Blank group 9.466 ± 0.177 11.627 ± 0.104 0.000 Blank group 23.832 ± 0.891 30.269 ± 0.329 0.004
GO group 8.447 ± 0.1131 10.897 ± 0.1244 0.043 GO group 26.342 ± 1.0421 31.085 ± 0.0374 0.008
UCMSC group 6.109 ± 0.0442 8.462 ± 0.0955 0.026 UCMSC group 29.022 ± 0.9732 31.223 ± 0.0915 0.153
GO + UCMSC group 5.139 ± 0.1833 5.401 ± 0.0866 0.039 GO + UCMSC group 37.439 ± 2.1553 35.865 ± 1.5376 0.447
1–6
Compared with the blank group, P values were 0.010, 0.000, and 1–6
Compared with the blank group, P values were 0.111, 0.017, and
0.000; 0.063, 0.031, and 0.000, respectively 0.001; 0.042, 0.025, and 0.007, respectively
International Orthopaedics (SICOT)
COL-II results
The COL-II serum results of the model are as follows: 13.475
± 0.342 ng/ml in the blank group, 14.127 ± 0.102 ng/ml in the
GO group, 15.589 ± 0.063 ng/ml in the UCMSC group, and
19.372 ± 0.063 ng/ml in the GO + UCMSC group.
The differences among the GO + UCMSC group, UCMSC
group, and blank group were highly statistically significant
(P < 0.01). The difference between the GO + UCMSC group
and the UCMSC group was highly statistically significant
(P < 0.01). The difference between the GO group and the
blank group was not statistically significant (P > 0.05).
The COL-II articular fluid results of the model are as fol-
lows: 8.308 ± 0.133 ng/ml in the blank group, 9.391 ±
0.350 ng/ml in the GO group, 11.652 ± 0.701 ng/ml in the
UCMSC group, and 14.127 ± 0.102 ng/ml in the GO +
UCMSC group.
The difference between the GO + UCMSC group and the
blank group was highly statistically significant (P < 0.01). The
differences among the GO group, UCMSC group, and blank
group were statistically significant (P < 0.05). The difference
between the GO + UCMSC group and the UCMSC group was
not statistically significant (P > 0.05).
The differences between the results of COL-II in serum and
articular fluid were as follows: the difference was highly sta-
tistically significant in the blank group and the GO + UCMSC
group (P < 0.01). The difference in the GO group was
Fig. 7 Micro-CT results after
treatment
statistically significant (P < 0.05). The difference in the
UCMSC group was not statistically significant (P > 0.05;
Table 4).
GAG results
The GAG serum results of the model are as follows: 23.832 ±
0.891 ng/ml in the blank group, 26.342 ± 1.042 ng/ml in the
GO group, 37.439 ± 2.155 ng/ml in the UCMSC group,
19.372 ± 0.063 ng/ml in the GO + UCMSC group.
The differences between the GO + UCMSC group and
blank group and the UCMSC group were highly statistically
significant (P < 0.01). The difference between the UCMSC
group and the blank group was statistically significant
(P < 0.05). The difference between the GO group and the
blank group was not statistically significant (P > 0.05).
The GAG articular fluid results of the model are as follows:
30.269 ± 0.329 ng/ml in the blank group, 31.085 ±
0.037 ng/ml in the GO group, 31.223 ± 0.091 ng/ml in the
UCMSC group, and 35.865 ± 1.537 ng/ml in the GO +
UCMSC group.
The difference between the GO + UCMSC group and the
blank group was highly statistically significant (P < 0.01). The
differences among the UCMSC group, GO group, and blank
group were statistically significant (P < 0.05). The difference
between the GO + UCMSC group and the UCMSC group was
statistically significant (P < 0.05).

The differences between the results of GAG in serum and
articular fluid were as follows: The differences were highly
statistically significant in the blank group and the GO group
(P < 0.01). The differences were not statistically significant in
the UCMSC group and the GO + UCMSC group (P > 0.05;
Table 5).
GO granular lubricant has no significant improvement in
the intra-articular environment of knee joint, and UCMSC has
a certain degree of improvement on improving inflammation
environment. The improvement results of NO, IL-6, TNF-α,
GAG, and COL-II were the best in the GO + MSC group, but
the improvement results of inflammatory cytokine levels in
serum and articular fluid were not consistent, especially the
differences of NO, IL-6, and TNF-α were greater.
Micro-CT scan results
The micro-CT scan results showed that although the articular
surface damage in each treatment group was repaired to a
certain extent, the trabecular bone growth was slightly loose.
New cartilage appeared in the defect area, but the cartilage
was thin and irregular. According to the results, the GO +
UCMSC group was the most effective in articular surface
repair. The effect of the UCMSC group was relatively deviat-
ed, and the cartilage morphology was irregular, while that of
GO group was even worse (Fig. 7).
Discussion
KOA is a type of aseptic inflammation. GAG and COL-II are
specific substances secreted by the cartilage, which can ex-
plain the recovery of cartilage function to a certain extent. The
control of the inflammatory reactions is also an important part
of the treatment of KOA. Changes in the cartilage can lead to
increased levels of inflammatory factors in the articular cavity.
IL-6, TNF-α, and NO are indicators of the inflammation level
[26–28]. According to the results, GO granular lubrication has
no effect on improving the intra-articular environment, and
UCMSCs have the effect of reducing the inflammatory factors
to a certain extent, but the improvement results of inflamma-
tory factors in the serum and joint fluid are not unified.
However, in terms of the overall trend, their results are con-
sistent. Similar to the treatment results of GAG and COL-II,
which are secreted by the cartilage, IL-6, TNF-α, and NO
levels were the most decreased in the GO + UCMSC group.
The GO + UCMSC group was the most effective group.
After treatment, the change in the inflammation level in the
articular cavity was consistent with the degree of cartilage
repair, which indicated that UCMSCs could improve the in-
flammation level and stabilize the intra-articular environment.
Although GO granular lubrication did not have a therapeutic
effect on the articular cartilage and biochemical environment,
International Orthopaedics (SICOT)
it could promote the therapeutic effect of UCMSCs as
scaffold-carrying material.
This research is still in the initial stage of exploration. At
present, only the biocompatibility of UCMSCs loaded with
GO granular lubrication and its therapeutic effect on the
KOA animal model has been proved. There were no adverse
reactions, no animal model death, and no tumour in the joint.
First of all, the research still lacks evaluation of the me-
chanical condition of the cartilage surface; therefore, the finite
element model can be used for comparative analysis, com-
bined with the biochemical level results to comprehensively
analyze the treatment with this method. Combined with the
biochemical level results, the treatment with this method can
be comprehensively analyzed. Secondly, the KOA model is
not perfect, and therefore, we should aim to simulate more
closely to the real clinical KOA patients to achieve more ac-
curate research results. Finally, further research should be
conducted on cartilage ion metabolism channels and mRNA
in the future [29, 30] to further understand the pathogenesis
and treatment of KOA, as well as the gait before and after
treatment and pain scores of animals, to understand the recov-
ery of knee function after treatment.
Conclusion
UCMSCs loaded with GO granular lubrication are a new com-
posite scaffold system for tissue engineering research, which
was established by combining the advantages of both
UCMSCs and GO. We hope to find a way to effectively delay
the onset age of KOA and even reverse its pathological
process.
Acknowledgments We thank LetPub for its linguistic assistance during
the preparation of this manuscript.
Authors’ contributions WX participated in all experiments and was a
major contributor in writing of the manuscript. WC provided theoretical
guidance for experiments. LA was the main designer of the experiment.
LR was responsible for the supply and detection of UCMSCs. WQ was
responsible for providing the GO granular lubricant. All authors read and
approved the final manuscript.
Funding information This work was supported by the National Natural
Science Foundation of China (project name: Research on mechanisms of
Kidney and Blood stasis KOA cartilage repair based on 3D GO nanoscale
scaffold culture of umbilical cord derived MSC 8187150461).
Data availability The datasets analyzed during the current study are avail-
able from the corresponding author on reasonable request.
Compliance with ethical standards According to the review
of the animal experiment center of Tianjin University of Traditional
Chinese Medicine, the animal experiment scheme and related materials
involved in the project meet the ethical requirements of experimental
animal welfare and animal experiment.
International Orthopaedics (SICOT)
Conflict of interest The authors declare that they have no conflict of
interest.
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