Ukai et al. Arthritis Research & Therapy(2021) 23:227
https://doi.org/10.1186/s13075-021-02611-x

RESEARCH ARTICLE

Open AccessComparison of properties determined using
electromechanical assessment (ArthroBST™) with macroscopic and histologicalproperties in symptomatic human articularcartilage of the hip
Taku Ukai1,2, Masato Sato1,2* , Shiho Wasai1,2, Takumi Takahashi1,2, Haruka Omura1,2 and Masahiko Watanabe1,2Abstract
Background: Cartilage degeneration is assessed using various methods. Although macroscopic evaluation candirectly measure cartilage degeneration, it cannot accurately assess cartilage properties. Histological examination is
one of the most accurate methods for evaluating cartilage degeneration. However, it is invasive and requires
collection of cartilage tissue. In contrast, the Arthro-BST™ probe can assess cartilage properties noninvasively. This
study aimed to evaluate the effectiveness of the Arthro-BST in assessing cartilage degeneration by comparing
macroscopic (International Cartilage Repair Society [ICRS] classification) and histological evaluations (modified
Mankin score and Osteoarthritis Research Society International [OARSI] histological grade).
Methods: Fourteen femoral heads were excised from 13 patients during surgery to treat hip osteoarthritis orfemoral fracture. The ICRS score was used for macroscopic evaluation of cartilage degeneration. The Arthro-BST wasapplied at sites matching the areas of cartilage damage. The sites assessed using the ICRS classification and ArthroBST were evaluated histologically (modified Mankin score and OARSI histological grade), and these were comparedwith the Arthro-BST results.
Results: The ICRS classification identified significant differences between grades 1 and 3 (p < 0.01), between grades
1 and 4 (p < 0.01), between grades 2 and 3 (p < 0.01), and between grades 2 and 4 (p < 0.01). Significant
correlations were observed between the Arthro-BST results and the ICRS score, modified Mankin score (structure,
cellularity, matrix staining, total score), and OARSI histological grade.
Conclusions: In the assessment of hip osteoarthritis, the Arthro-BST results correlated with those of macroscopic
and histological evaluations. The Arthro-BST is useful for assessing hip osteoarthritis and may be helpful for
noninvasive assessment of cartilage degeneration.
Keywords: Osteoarthritis, Arthro-BST, ICRS classification, Modified Mankin score, OARSI histological system* Correspondence: sato-m@is.icc.u-tokai.ac.jp
1
Department of Orthopedic Surgery, Surgical Science, Tokai University Schoolof Medicine, 143 Shimokasuya, Bohseidai, Isehara, Kanagawa 259-1193, Japan
2
Center for Musculoskeletal Innovative Research and Advancement (C-MiRA),
Tokai University Graduate School, Shimokasuya, Isehara, Kanagawa 259-1193,
Japan© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to thedata made available in this article, unless otherwise stated in a credit line to the data.

Ukai et al. Arthritis Research & Therapy(2021) 23:227

Background
Osteoarthritis (OA) is a common form of arthritis
among older people, and the number of patients with
OA is increasing worldwide. Although OA is not a lifethreatening disease, it affects daily activities and qualityof life. Cartilage is one of the most difficult tissues to regenerate because of its avascular nature. Therefore, detecting early degeneration of articular cartilage isnecessary for the prevention and treatment of OA. Various diagnostic methods, such as radiography [1], macroscopic imaging [2], magnetic resonance imaging (MRI)[3], and histological evaluation [4, 5], are used for evaluating OA.
Although radiography is the most frequently usedtechnique for evaluating OA through assessment of joint
space and osteophyte formation, this method cannot be
used to evaluate the macroscopic changes and propertiesof articular cartilage. Arthroscopy is used widely fortreating cartilage degeneration, and although it can beused to assess cartilage degeneration directly, it cannot
be used to evaluate cartilage properties. MRI has recently been used for assessing cartilage degeneration.
We have focused on the noninvasive assessment of cartilage degeneration and have reported the usefulness of
MRI for assessing knee OA using T2 mapping and diffusion tensor imaging [3]. Although MRI can be used toassess cartilage degeneration noninvasively, it is difficult
to assess cartilage degeneration when the cartilage damage is of a mixed nature. Histological evaluation can beused to assess cartilage degeneration accurately, but it
involves the destruction of normal cartilage.
To overcome these disadvantages, nondestructive devices have been developed to assess cartilage degeneration [6–21]. We explored the literature on theassessment of cartilage degeneration that used laserinduced photoacoustic measurement (LIPA) instruments[21]. These devices can assess cartilage degeneration
without the need to collect tissue samples. We have previously compared LIPA with histological evaluation andreported that LIPA can be used to assess cartilage degeneration and viscoelastic properties [21].
Articular cartilage contains proteoglycans that haveelectromechanical properties [22]. Interstitial water contains positive mobile ions, such as Na+ and K+, whichbalance the fixed negative electric charge from proteoglycans [22]. The mechanical compression of articularcartilage generates streaming potentials induced bywater flowing out from articular cartilage [23], and thesestreaming potentials reflect cartilage integrity and degeneration [24–27]. Taking advantage of this property, theArthro-BST instrument (Biomomentum, Laval, QC,
Canada) was invented for assessing the streaming potentials of articular cartilage. This apparatus is used duringarthroscopy and induces streaming potentials using 37

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microelectrodes with the help of the spherical indenterof the tip. The effectiveness of the Arthro-BST for assessing the properties of articular cartilage of the knee has
been reported previously [28–31]. However, no study
has evaluated the effectiveness of the Arthro-BST for
assessing the hip by evaluating the macroscopic andhistological properties simultaneously.
This study aimed to evaluate the effectiveness of theArthro-BST for evaluating the hip by comparing its findings with macroscopic findings. We used the International Cartilage Repair Society (ICRS) classification
system [2] and histological findings such as the modified
Mankin histological score [32] and Osteoarthritis Research Society International (OARSI) histopathology assessment system [5].

Methods
Sample source

Tissue was obtained from patients who had been diagnosed with OA or femoral fracture of the hip and who
underwent total hip arthroplasty or bipolar hip arthroplasty at the authors’ institution. After resection of thefemoral head of the hip, 14 femoral heads of 13 patientswere evaluated (Table 1). This study was performed after
approval from the research review committee at the author’s institution (approval number: 18R-187). All patients provided written informed consent.
Assessment procedure

After resection of the femoral head, cartilage lesions
were assessed macroscopically using the ICRS classification [2]. The same sites of cartilage lesions were assessedhistologically using the modified Mankin score [32] andOARSI grade [5].
Macroscopic assessment

After dissection of the femoral head, the assessment
points were marked with the help of photographs(Fig. 1). Two experienced orthopedic surgeons separately performed a macroscopic assessment of 14 femoral heads. Sixty-one locations of the femoral head
were used to assess the ICRS classification (Table 2).
Each femoral head was assessed for cartilage degeneration on the day of surgery.
Electromechanical assessment

The Arthro-BST measures streaming potentials generated during rapid compression of the articular cartilage
with an array of 37 microelectrodes lying on a hemispherical indenter (effective radius of the tip = 3.18 mm,
5 microelectrodes/mm2) [29]. The device measures aquantitative parameter (QP), which corresponds to thenumber of microelectrodes in contact with the cartilage
when the sum of all electrode potentials reaches 100 mV

Ukai et al. Arthritis Research & Therapy(2021) 23:227

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Table 1 Patient demographics
Patient number

Age (years)

Sex

Body mass index (kg/m2)

Diagnosis

Kellgren–Lawrence classification

1

72

F

26.2

Osteoarthritis

3

2

57

F

24.4

Osteoarthritis

3

3

65

F

22

Osteoarthritis

3

4

60

F

34.9

Osteoarthritis

4

5

83

F

18.6

Osteoarthritis

4

6

74

F

23.7

Osteoarthritis

4

7

82

F

17.2

Femoral neck fracture

1

8

67

F

26

Osteoarthritis

3

9

84

F

23

Femoral neck fracture

1

10

64

F

23.1

Osteoarthritis

4

11

54

M

24.8

Osteoarthritis

4

12

70

F

27.4

Osteoarthritis

4

Femoral neck fracture

1

13

71
14

F
55

23.2
F

24.4

[30]. A high QP indicates strong electromechanicalproperties and normal cartilage, and a low QP indicatesweak electromechanical properties and degenerated
cartilage.
The resected femoral heads were placed onto a cylindrical platform and assembled into a testing chamberusing screws. A single electromechanical measurement
was performed manually at each position of the grid

Osteoarthritis

3

using the Arthro-BST. Measurements were performedon the day of surgery (Fig. 1).
Histological assessment

Twenty-five samples were used for histological assessment. Two experienced orthopedic surgeons separately
performed a histological assessment of each sample. The
tissue samples were cut into sections by making cuts

Fig. 1 Cartilage tissue assessment. A The ICRS classification was used to assess the cartilage of the femoral head (see Table 1 for the definition of
the grades). B Schematic drawing of the Arthro-BST. The Arthro-BST induces streaming potentials using 37 microelectrodes. C The Arthro-BST wasused to assess the same points assessed by the ICRS classification. D Cartilage sections were made by cutting perpendicular to the same points
assessed using the ICRS classification and Arthro-BST

Ukai et al. Arthritis Research & Therapy(2021) 23:227

Table 2 ICRS classification as described by Mainil-Varlet et al. [2]GradeProperty

1

Superficial lesions, fissures and cracks, soft indentation2

Defects that extend to less than 50% in depth

3

Defects that extend to more than 50% in depth

4Complete loss of cartilage thickness, bone only

perpendicular to the cartilage surface and then fixed in 4%
paraformaldehyde for 1 month. After decalcification for 2
months using distilled water (pH 7.4) containing 10% ethylenediaminetetraacetic acid, the tissue was embedded inparaffin wax and sectioned perpendicularly through thecenter of the cartilage damage. Each section was stainedwith Safranin O dye for histological evaluation of glycosaminoglycans [33]. For histological assessment, sections
stained with Safranin O were assessed using the modified
Mankin score [32] and the OARSI histopathology assessment system (grade 0, surface intact, cartilage morphology
intact; grade 1, surface intact; grade 2, surface discontinuity; grade 3, vertical fissures (clefts); grade 4, erosion; grade
5, denudation; grade 6, deformation) [5]. Two orthopedic
surgeons of the Japanese Orthopedic Association independently performed the histological assessment. The
modified Mankin score was determined by adding thescores of the parameters (structure, cellularity, matrix
staining, and tidemark integrity), with 0 as the lowest
score and 15 as the highest score (Table 3).
Statistical analysis

Kruskal–Wallis followed by the Bonferroni post hoc test
was used to compare the ICRS grade and Arthro-BST result (QP). Spearman’s rank correlational analysis was used
to identify significant relationships between the Arthro-

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BST QP and the ICRS grade, modified Mankin score, andOARSI histological grade. Interobserver reliability wastested using intraclass correlation coefficients (ICCs), andtheir 95% confidence intervals (CIs) were used to assess thereliability of the macroscopic and histological assessments.
All tests were performed at a significance level of p < 0.05.
Analyses were performed using IBM SPSS Statistics for
Windows version 26 (IBM Corp., Armonk, NY, USA).

Results
Comparison between the Arthro-BST and themacroscopic assessment results

The ICRS grades of the cartilage lesion for all samples
were grade 1 (n = 23), grade 2 (n = 18), grade 3 (n = 13),and grade 4 (n = 7). The interobserver reliability of the
ICRS classification was 0.973 (95% CI, 0.956–0.984)(Additional file 1). The QPs for the grades were as follows: grade 1, 14.1 ± 5.5; grade 2, 15.6 ± 3.4; grade 3, 7.8± 3.2; and grade 4, 2 ± 2.5. Significant differences wereobserved between grades 1 and 3 (p < 0.01), between
grades 1 and 4 (p < 0.01), between grades 2 and 3 (p <0.01), and between grades 2 and 4 (p < 0.01) (Fig. 2).
Relationship between the Arthro-BST QP and themacroscopic assessment

The QP decreased as the ICRS grade increased, and thecorrelation between these variables was significant (p <0.01) (Fig. 3).
Relationship between the Arthro-BST and the histologicalassessment
Modified Mankin score: structure

The values for the structure parameter of the modified
Mankin score were 0 (n = 3), 1 (n = 8), 2 (n = 6), 3 (n =Table 3 Modified Mankin score for evaluation of articular cartilage degeneration as described by Henson and Vincent [32]Score

Structure

Cellularity

Matrix staining

Tidemark
integrity

Score
0

Smooth surface

Normal arrangement

Normal staining

Normal andintactClustering in the superficial layer or loss of cells up
to 10%

Slight loss of stain

Disrupted

Disorganization or loss up to 25%

Moderate loss ofstain

Normal appearance
Score
1
Score
2

Roughened surface
Single crack or area of delamination
Multiple cracks
Moderate delamination

Score
3

Fragmentation in cartilage or severedelamination

Cell rows absent or loss up to 50%

Severe loss of stain

Score
4

Loss of fragments

Very few cells present

No stain present

Score
5

Complete erosion to tidemark

Score
6

Erosion beyond tidemark

Ukai et al. Arthritis Research & Therapy(2021) 23:227

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Fig. 2 Arthro-BST assessment and ICRS classification. The QP decreased as the ICRS grade increased. Significant differences were observed for
ICRS grades 1 and 3 (p < 0.01), grades 1 and 4 (p < 0.01), grades 2 and 3 (p < 0.01), and grades 2 and 4 (p < 0.01)

5), 4 (n = 1), 5 (n = 0), and 6 (n = 2). The interobserver
reliability of the score for structure was 0.877 (95% CI,
0.725–0.946) (Additional file 2). The QPs for the scores
were as follows: score 0, 18 ± 2.6; score 1, 17.9 ± 3.3;score 2, 16 ± 2.6; score 3, 9.8 ± 4.4; score 4, 14; andscore 6, 9.5 ± 3.5. The QP decreased as the structure
score increased, and the correlation between these wassignificant (p < 0.01) (Fig. 4).
Cellularity

The values for the cellularity parameter of themodified Mankin score were 0 (n = 1), 1 (n = 10), 2(n = 5), 3 (n = 6), and 4 (n = 3). The interobserver
reliability of the cellularity score was 0.9 (95% CI,
0.775–0.956) (Additional file 2). The QPs for thescores were as follows: score 0, 16; score 1, 16.7 ±

4.4; score 2, 17.6 ± 2.2; score 3, 11.1 ± 4; and score4, 11.7 ± 4.5. The QP decreased as the cellularity
score increased, and the correlation between thesewas significant (p < 0.01) (Fig. 4).
Matrix staining

The values for the matrix staining parameter of themodified Mankin score were 0 (n = 2), 1 (n = 10), 2(n = 8), 3 (n = 2), and 4 (n = 3). The interobserver
reliability for the matrix staining score was 0.874(95% CI, 0.717–0.944) (Additional file 2). The QPs forthe score were as follows: score 0, 20 ± 4.2; score 1,
15.9 ± 4; score 2, 14 ± 5; score 3, 13.5 ± 3.5; andscore 4, 11.7 ± 4.5. The QP decreased as the matrix
staining score increased, and the correlation between
these was significant (p < 0.01) (Fig. 4).

Fig. 3 Scatter plot of the correlation between the Arthro-BST results and the ICRS classification. Each diamond represents the QP according to
the ICRS grade in an individual hip. A significant strong correlation was observed between the Arthro-BST and the ICRS classification (R2 = 0.4527)

Ukai et al. Arthritis Research & Therapy(2021) 23:227

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Fig. 4 Scatter plot of the correlations between the Arthro-BST and the modified Mankin score. Each diamond represents the QP values for the
structure, cellularity, matrix staining, tidemark, and total score in an individual hip. The Arthro-BST result correlated significantly with structure (R2= 0.4034), cellularity (R2 = 0.2403), matrix staining (R2 = 0.1803), and total score (R2 = 0.2589)

Tidemark

The values for the tidemark parameter of the modified
Mankin score were 0 (n = 15) and 1 (n = 10). The interobserver reliability for the tidemark score was 0.868(95% CI, 0.704–0.942) (Additional file 2). The QPs forthe scores were as follows: score 0, 15.1 ± 5.1; score 1,
14.7 ± 3.9. The correlation between the QP and the tidemark score was not significant (Fig. 4).
Total score

The interobserver reliability of the total score was 0.93
(95% CI, 0.844–0.969) (Additional file 2). The QP decreased as the total modified Mankin score increased,
and the correlation between these was significant (p <0.01) (Figs. 4 and 5).
OARSI histological grade

The OARSI grades of cartilage lesions were as follows:
grade 0 (n = 2), grade 1 (n = 6), grade 2 (n = 8), grade 3(n = 1), grade 4 (n = 0), and grade 5 (n = 8). The interobserver reliability for the OARSI histological grade was
0.903 (95% CI, 0.782–0.957) (Additional file 3). The QPs

for the grades were as follows: grade 0, 16.5 ± 0.7; grade
1, 17.3 ± 4.2; grade 2, 17.6 ± 1.9; grade 3, 7; and grade 4,
11 ± 3.8. The QP decreased as the OARSI grade increased, and the correlation between these was significant (p < 0.01) (Fig. 6).

Discussion
Our results demonstrated that the Arthro-BST can distinguish between ICRS grades 1 and 3, between grades 1
and 4, between grades 2 and 3, and between grades 2
and 4. There was a significant correlation between the
Arthro-BST QP and the ICRS grades as well as between
the Arthro-BST QP and the modified Mankin scores(structure, cellularity, matrix staining, total score) andOARSI histological grade.
Various methods are used for the evaluation of cartilage degeneration. MRI has recently been used for theevaluation of OA. We have previously reported that
Outerbridge grades correlate with MRI variables such as
diffusion tensor imaging and T2 mapping [3]. Although
the biggest advantage of MRI is its ability to assess cartilage degeneration noninvasively, it is not capable ofUkai et al. Arthritis Research & Therapy(2021) 23:227

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Fig. 5 Histological assessment: representative Safranin O-stained sections for four parameters of the modified Mankin score and thecorresponding QP. A The modified Mankin score of the cartilage section was 1 (structure, 1; cellularity, 0; matrix staining, 0; tidemark, 0; total, 1).
The QP of the same point was 23. B The modified Mankin score of the cartilage section was 5 (structure, 0; cellularity, 2; matrix staining, 2;
tidemark, 1; total, 5). The QP of the same point was 16. C The modified Mankin score of the cartilage section was 9 (structure, 4; cellularity, 3;matrix staining, 2; tidemark, 0; total, 9). The QP of the same point was 13. D The modified Mankin score of the cartilage section was 15 (structure,
6; cellularity, 4; matrix staining, 4; tidemark, 1; total, 15). The QP of the same point was 7

assessing cartilage properties; hence, other methods thatcan evaluate cartilage properties without the need tosample cartilage tissue are needed.
Some studies have reported that the Arthro-BST QP
correlates with the ICRS grade [29, 30, 34, 35] and Mankin score [29, 30]. Although the Arthro-BST could not
distinguish ICRS grade 1 from 2 and grade 3 from 4 inour results, the QP correlated significantly with the ICRS
grade. Similarly, Hadjab et al. [28] reported that the QP
did not correlate significantly between ICRS grades 0

and 2, which seems reasonable because the ICRS grading
system cannot distinguish small differences in cartilage
damage [36] and because tissues affected by OA canhave lesions with mixed grades of cartilage degeneration.
We did not measure cartilage thickness in this study,
and we found no significant differences between ICRS
grades 1 and 2 or between grades 3 and 4. However, acomparison of the Arthro-BST results and the ICRS
score is important. The Arthro-BST must be used underarthroscopy because the embedded sensors must be in

Fig. 6 Scatter plot of the correlation between the Arthro-BST results and the OARSI histopathological score. Each diamond represents the QP
according to the OARSI grade in an individual hip. A significant correlation was observed between the Arthro-BST results and the OARSI
histopathological score (R2 = 0.3868)

Ukai et al. Arthritis Research & Therapy(2021) 23:227

direct contact with the cartilage. Although the ArthroBST could not distinguish between ICRS grades 1 and 2
or between grades 3 and 4 in our study, we consider that
this apparatus would be useful for hip OA because it candistinguish early OA (ICRS grade 1) from moderate OA(ICRS grade 2), early OA from severe OA (ICRS grade 3or 4), and moderate OA from severe OA.
Cartilage tissue is classified into articular or hyaline
cartilage and fibrous cartilage. Healthy articular cartilage
comprises mainly hyaline cartilage, fibrous cartilage
comprises mainly type I collagen, and hyaline cartilage
comprises mainly type II collagen. Fibrous cartilage isfrequently seen after injury and in degenerated cartilage
tissue. The deposition of fibrous cartilage in place of articular cartilage is an inferior change that can lead tosecondary OA. Distinguishing between fibrous and hyaline cartilage is difficult when using only the ICRS classification, but assessing the composition of regenerative
tissue is necessary to prevent secondary OA. Chondrocyte proliferation appears during the early stages of OA[37], and the proteoglycan content decreases before collagen content decreases [37–39]. These changes induce
fibrillation and fissures, which affect the mechanicalstrength of articular cartilage [40, 41]. Therefore, it isimportant to determine whether the Arthro-BST resultscorrelate with the histological data.
As for the results of the histological assessment, someauthors have reported that the QP correlates significantly with the total Mankin score [29, 30]. The Mankinscore includes five parameters (structure, cellularity,
matrix staining, tidemark, total score), and most reports
have assessed only the QP and total score. We foundthat the total score and other parameters correlated significantly with the QP (Fig. 4). We have previously studied the effectiveness of LIPA [21]. LIPA is based on theuse of photoacoustic waves and can assess viscoelastic
properties without sampling cartilage tissue. We previously reported that the LIPA results correlated strongly
with the ICRS grade, although we found no correlation
between the LIPA results and the overall Mankin score[21]. Compared with LIPA, the Arthro-BST QP had
stronger correlations with the total score as well as withstructure, cellularity, and matrix staining. Therefore, we
believe that the Arthro-BST is preferable to the LIPA for
assessing cartilage degeneration.
Pritzker et al. [5] were the first to report the OARSI
histological system. Some studies have reported excellent
correlations between the Mankin score and the OARSI
histological grade [42–46]. Compared with the modified
Mankin score, the OARSI histological grade focuses
more on structural parameters. The Mankin score does
not have a staging component [42] and has limited usefulness for assessing mild and moderate OA [47]. In
contrast, the OARSI system can distinguish between

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early and moderate OA [2]. Subchondral bone changes
occur during the first stage of OA [48, 49], and thesechanges affect the pathogenesis of OA [50–53]. Finnilä
et al. [54] reported a high correlation between the
OARSI grade and subchondral plate thickness. Therefore, we used both histological scores in this study to assess each stage of OA accurately. We found a significant
correlation between the QP and the OARSI histologicalgrade and that the Arthro-BST was able to assess all
grades of OA. Therefore, we believe that the ArthroBST is useful for the simultaneous evaluation of macroscopic and cartilage properties. This device may also
help in decision-making about the best method for cartilage regeneration and for assessing regenerating tissue.
There are some limitations to this study. First, someauthors have already reported an association between
the Arthro-BST results and the measures of OA. However, some of these authors have used cartilage fromgoats [31] or from human knees for evaluation [27–30].
To our knowledge, no studies have reported on the associations between the Arthro-BST results and OA measures in human cartilage of the hip. In addition, otherauthors have used human cartilage that underwent
freeze–thaw cycles, which may have influenced themacroscopic appearance and histological properties of
the cartilage tissue. Second, the assessments of the ICRS
classification score, modified Mankin score, and OARSI
histological score varied somewhat, which may have affected the results. However, the assessments were performed by two different evaluators, and all ICCs were >0.7, which indicates high reproducibility.

Conclusions
The Arthro-BST can distinguish between ICRS grades 1
and 3, grades 1 and 4, grades 2 and 3, and grades 1 and3. The Arthro-BST findings correlated with the macroscopic and histological assessment results. This apparatus may be helpful for performing macroscopic andhistological assessments simultaneously, which may be
useful for the noninvasive diagnosis of OA.
Abbreviations
CI: Confidence interval; ICC: Intraclass correlation coefficient;
ICRS: International Cartilage Repair Society; LIPA: Laser-induced pulse
acoustic; MRI: Magnetic resonance imaging; OA: Osteoarthritis;OARSI: Osteoarthritis Research Society International; QP: Quantitative
parameter

Supplementary Information
The online version contains supplementary material available at https://doi.
org/10.1186/s13075-021-02611-x.
Additional file 1. Individual scoring data of the ICRS classification.
Additional file 2. Individual scoring data of the modified Mankin score.
Additional file 3. Individual scoring data of the OARSI histopathologicalsystem.

Ukai et al. Arthritis Research & Therapy(2021) 23:227

Acknowledgements
The authors wish to acknowledge the Support Center for Medical Researchand Education of Tokai University Hospital for technical assistance. The
authors wish to acknowledge Professor Hiroyuki Kobayashi for statisticalanalysis advice.
Authors’ contributions
MS contributed to the conception and design of the study. TU, SW, and HO
acquired and analyzed the data. TU and SW performed the orthopedic
surgery and graded the cartilage damage. SW and TT operated the ArthroBST. TU, SW, and TT contributed to the interpretation of the data. TU wrote
the first version of the manuscript, and all other authors revised it criticallyfor important intellectual content. All authors have read and approved thefinal manuscript. All authors agreed to be accountable for all aspects of thework.
Funding
This work was supported by a grant from the Japan Orthopaedics andTraumatology Research Foundation (no. 458).
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.

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9.

10.

11.

12.

13.

Declarations
14.
Ethics approval and consent to participate
This study was performed in accordance with the Declaration of Helsinki andits later amendments. The study was approved by the ethics committee of
the Institutional Review Board (18R-187). Written informed consent was
obtained from all participants.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.

15.

16.

17.

Received: 18 February 2021 Accepted: 20 August 2021
18.
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