The American Journal of Sports

Medicine http://ajs.sagepub.com/

Clinical Outcomes After Cell-Seeded Autologous Chondrocyte Implantation of the Knee: When Can
Success or Failure Be Predicted?
Jan M. Pestka, Gerrit Bode, Gian Salzmann, Mathias Steinwachs, Hagen Schmal, Norbert P. Sdkamp and Philipp
Niemeyer
Am J Sports Med 2014 42: 208 originally published online October 28, 2013
DOI: 10.1177/0363546513507768

The online version of this article can be found at:

http://ajs.sagepub.com/content/42/1/208

Published by:

http://www.sagepublications.com

On behalf of:
American Orthopaedic Society for Sports Medicine

Additional services and information for The American Journal of Sports Medicine can be found at:

Email Alerts: http://ajs.sagepub.com/cgi/alerts

Subscriptions: http://ajs.sagepub.com/subscriptions

Reprints: http://www.sagepub.com/journalsReprints.nav

Permissions: http://www.sagepub.com/journalsPermissions.nav

>> Version of Record - Jan 2, 2014

OnlineFirst Version of Record - Oct 28, 2013

What is This?

Downloaded from ajs.sagepub.com by guest on April 8, 2016

Clinical Outcomes After Cell-Seeded
Autologous Chondrocyte Implantation
of the Knee
When Can Success or Failure Be Predicted?
Jan M. Pestka,*y MD, Gerrit Bode,y MD, Gian Salzmann,y MD, Mathias Steinwachs,y MD,
Hagen Schmal,y MD, PhD, Norbert P. Sudkamp,y MD, PhD, and Philipp Niemeyer,y MD, PhD
Investigation performed at the Department of Orthopedic Surgery and Traumatology,
Freiburg University Hospital, Freiburg, Germany

Background: Autologous chondrocyte implantation (ACI) has been associated with satisfying results. Still, it remains unclear
when success or failure after ACI can be estimated.
Purpose: To evaluate the clinical outcomes of cell-seeded collagen matrixsupported ACI (ACI-Cs) for the treatment of cartilage
defects of the knee at 36 months and to determine a time point after ACI-Cs at which success or failure can be estimated.
Study Design: Cohort study; Level of evidence, 3.
Methods: A total of 80 patients with isolated full-thickness cartilage defects of the knee joint treated with ACI-Cs were prospec-
tively assessed before surgery as well as postoperatively by use of the International Knee Documentation Committee (IKDC) score
and Lysholm knee score.
Results: Preoperative IKDC and Lysholm scores increased from 49.6 and 59.5, respectively, to 79.1 and 83.5, respectively, at
36 months. Only half the patients (46.6%) with poor IKDC scores (ie, \70) at 6 months postoperatively showed continued
poor or fair scores at 36 months follow-up. The probability of poor scores at 36 months after surgery further increased to
0.61 and 0.81, respectively, when scores were persistent at 12 and 24 months. All 3 patients (100%) with good IKDC scores
(ie, 81-90) at 6 months after surgery showed constant or even improved scores at 36 months follow-up. Ninety-one percent
of patients with good and excellent scores at 12 months and 83% of patients with good and excellent scores at 24 months (a
total of 23 and 37 patients, respectively) were able to maintain these scores at 36 months follow-up. Similar results were obtained
for the Lysholm score.
Conclusion: With regard to the improvements in functional outcomes after ACI-Cs at 36 months after surgery, the technique
described here appears to lead to satisfying and stable clinical results. This study helps the treating physician to predict the like-
liness of further clinical improvements or constant unsatisfactory results after ACI. In patients with good/excellent scores shortly
after surgery, deterioration of the knees condition is rarely found. For patients with poor and fair postoperative scores, clinical
outcomes are more difficult to predict, especially during the first year after the procedure.
Keywords: autologous chondrocyte implantation; articular cartilage; knee joint; IKDC; Lysholm; success; failure

Autologous chondrocyte implantation (ACI) is a well-

*Address correspondence to Jan M. Pestka, MD, Department of
Orthopedic Surgery and Traumatology, Freiburg University Hospital,
Hugstetter Str. 55, D - 79095 Freiburg, Germany (e-mail: jan.pestka@
uniklinik-freiburg.de).
y
Department of Orthopedic Surgery and Traumatology, Freiburg Uni-
versity Hospital, Freiburg, Germany.
One or more of the authors has declared the following potential con-
flict of interest or source of funding: Funding was provided by Deutsche
Forschungsgesellschaft (DFG) and the AO Foundation Research Fund.
The American Journal of Sports Medicine, Vol. 42, No. 1
DOI: 10.1177/0363546513507768
2013 The Author(s)
established and accepted surgical procedure for the treat-
ment of cartilage defects of the knee joint.3,6,13 Short-
term and midterm results regarding this procedure have
been studied in depth and reveal satisfying outcomes.3,13
Over the years, the initial first-generation ACI technique
in which a periosteal flap was used to cover and seal the
defect has been modified because of harvest site morbidity
and graft hypertrophy.7,20 This led to the development of
second- and third-generation techniques in which in sec-
ond-generation ACI, a collagen membrane is used to cover
the cartilage defect after chondrocyte application to the

208
Downloaded from ajs.sagepub.com by guest on April 8, 2016
Vol. 42, No. 1, 2014
cartilage defect.7 In brief, in third-generation ACI, chondro-
cytes are embedded into the 3-dimensional collagen struc-
ture of the membrane, which is subsequently fitted into
the cartilage defect.8 In comparison with all 3 generations,
cell-seeded collagen matrixsupported ACI (ACI-Cs) repre-
sents a novel technical development. Use of a collagen-based
membrane avoids graft hypertrophy and reduces operative
time. In contrast to other third-generation ACI techniques,
the cells are seeded within the membrane, not beneath it.
Chondrocytes are transferred manually onto the membrane
just before implantation by the surgeon. As the seeded
membrane is initially attached mechanically while stable
onto the cartilage defect floor, it can progressively fill
the defect, while the construct can adapt to the local
topology.27,28
Only recently have preliminary 2-year results of 59 con-
secutive patients treated with ACI-Cs for cartilage defects
of the knee joint been reported.20 These are noteworthy, as
the technique resulted in a significant improvement in
patients clinical results after 24 months in comparison
with preoperative results. Absolute International Knee
Documentation Committee (IKDC) and Lysholm scores
were in the range of earlier reported data for the use of
ACI for full-thickness cartilage defects of the knee by dif-
ferent technical modifications.1,10,18 Furthermore, while
a number of studies reported on the dynamics of postoper-
ative results both from a histological as well as from a clin-
ical point of view up to 3 years after surgery, it was
uncertain if superior or inferior clinical results could be
expected over the course of the third year after ACI-
Cs.4,26 Therefore, the present study was initiated to evalu-
ate midterm outcomes including a total of 80 patients con-
secutively followed for a period of 36 months after ACI-Cs.
The aim of the present study was to present prospective
clinical results of a large cohort of 80 patients treated with
ACI-Cs and to further complete our previously presented
2-year results.20 Additionally, this study aimed to evaluate
different time points in the clinical course after ACI when
definite success or failure after ACI can be estimated. The
patients individual course was evaluated with regard to the
probability of final failure or success based upon IKDC and
Lysholm scores at different time points. This seems of high
clinical relevance, as it might support important decisions
during the clinical course after ACI such as indications for
revision surgery or patients return to physical activity.
MATERIALS AND METHODS
Patient Cohort
Between October 2005 and September 2008, 83 consecutive
patients with circumscribed, full-thickness cartilage defects
of the knee joint, graded III and IV according to the Interna-
tional Cartilage Repair Society (ICRS) classification,24 were
treated with ACI-Cs. All patients were enrolled in this study
before surgery and evaluated using the Lysholm16 and IKDC
scores.9 Previously defined subgroups for the IKDC score
were applied in which poor scores were \70, fair scores
ranged from 71 to 80, good scores ranged from 81 to 90,
Downloaded from ajs.sagepub.com by guest on April 8, 2016
Predicting Success or Failure of ACI at 36 Months 209
and scores were considered excellent if .90.9 Subgroups
for the Lysholm score consisted of poor scores of \65 points
to fair scores ranging from 65 to 83 points; good scores
were defined as 84 to 94 points, whereas excellent scores
were defined as 95 points.2 Follow-up evaluations were per-
formed at 6, 12, 24, and 36 months after surgery. At the time
of data collection, 80 patients had reached a follow-up of 36
months. Initial clinical results of 59 patients at 24 months
have been reported earlier.20 Complete preoperative and
postoperative data were available for 80 of 83 patients
(follow-up rate, 96.4%). Failure was defined as an improve-
ment in the IKDC and/or Lysholm score of less than 10%
or worsening knee function at 36 months follow-up in com-
parison with preoperative scores.
In all patients, indications for ACI were determined
during routine arthroscopic surgery of the affected knee
joint. Generally, ACI was performed in defects that were
greater than 3 cm2 in size, while in smaller defects, arthro-
scopic microfracturing was preferred. Exclusion criteria for
ACI-Cs in this study were corresponding (kissing) carti-
lage lesions, uncontained defects, and defects of the sub-
chondral bone plate exceeding a depth of 3 to 4 mm.
During arthroscopic surgery, chondrocytes were harvested
using a standardized cartilage biopsy tool (Storz, Tuttlin-
gen, Germany) from the intercondylar notch.20 In all
patients, ACI-Cs was performed as described earlier.27,28
In brief, between 1 and 2 million chondrocytes/cm2 per
defect (CartiGro Autologous Chondrocytes, MetreonBio-
products GmbH, Freiburg, Germany) were applied 5 to
10 minutes before transplantation to the rough side of
a porcine type I/III collagen membrane (Chondro-Gide,
Geistlich, Wolhusen, Switzerland). Details of the surgical
technique have been reported.28
After surgery, a standardized protocol11,20 was applied
that included continuous passive motion from day 1 after
surgery to 6 weeks postoperatively for up to 4 hours per
day. Limited weightbearing was recommended for 6 weeks
after ACI-Cs. Weightbearing was increased to full weight-
bearing 9 weeks after surgery. Individual limits of flexion
were additionally established depending on the exact
defect location to avoid early exposure of the regenerative
cartilage to axial compression and shear forces.
Statistical Analysis
Significant differences between individual time points of
the present study as well as cohorts of patients with
respect to the defect location (medial and lateral femoral
condyles, trochlea, and patella) were evaluated using
1-way analyses of variance (ANOVA) for all parametric
data (IKDC and Lysholm scores). The significance level
was P \ .05 for all analyses. P values for results after 36
months in comparison with different time points preopera-
tively and 6, 12, and 24 months postoperatively were calcu-
lated using the Wilcoxon signed-rank test to compare
paired samples. For all statistical analyses, the software
SPSS version 16.0 (IBM, Armonk, New York) was used
together with GraphPad Prism software (version 5, Graph-
Pad Software, La Jolla, California) and Microsoft Excel XP
(Microsoft, Redmond, Washington).
210 Pestka et al The American Journal of Sports Medicine

TABLE 1 and significant increase in both the IKDC and Lysholm

Characteristics of Patients (N = 80) and Defects (N = 106)a scores was observed over time up to the studys end point
at 36 months. To objectify decreases or increases in scores
Mean 6 Standard during the course of observation, the Wilcoxon test was used.
n (%) Deviation Range

Sex, M/F 46/34 (57.5/42.5) IKDC and Lysholm Scores at Different Time Points
Age at ACI, y 37.9 6 8.7 17.7-57.6
BMI, kg/m2 24.2 6 3.3 18.3-35.2
in Relation to Defect Location
No. of defects
The IKDC and Lysholm scores were evaluated with respect
1 lesion 57 (71.3)
2 lesions 22 (27.5)
to various defect locations at different time points. Signifi-
.2 lesions 1 (1.3) cant differences with regard to the locations analyzed
Defect size, cm2 4.6 6 1.7 1.0-8.8 were found neither for the IKDC nor for the Lysholm score.
\2 5 (4.7) When differences in scores preoperatively and 36 months
2-4 44 (41.5) postoperatively with respect to defect location (D IKDC
.4 57 (53.8) and D Lysholm) were assessed, significant differences
Defect location were found (Figure 2). One-way ANOVA of D IKDC var-
MFC 43 (40.6) iances revealed significant differences between all locations
LFC 10 (9.4) analyzed (P \ .001). Similar results were obtained for D
Patella 31 (29.2)
Lysholm in which all locations analyzed showed significant
Trochlear groove 22 (20.8)
Defect origin
differences with the exception of the trochlea versus patella,
Degenerative 41 (51.3) where there was no statistical significance (P = .13).
Posttraumatic 26 (32.5)
Traumatic 13 (16.3)
Failure Rate
a
ACI, autologous chondrocyte implantation; BMI, body mass The failure rate was defined as an improvement in the
index; F, female; LFC, lateral femoral condyle; M, male; MFC,
IKDC and/or Lysholm score of less than 10% or worsening
medial femoral condyle.
knee function at 36 months follow-up in comparison with
preoperative scores. Immediate postoperative complica-
RESULTS tions (eg, infection) were not observed and therefore had
no effect on the failure rate. A minority of 10 patients
Patient Characteristics (12.5%) failed the procedure. The mean age of these
patients was 40.4 6 8.5 years, 50% were male, and all
A total of 80 patients were included in the present study. but 1 were nonsmokers. The mean defect size did not differ
The mean age at the time of surgery was 37.9 6 8.7 years, significantly from the entire cohorts, with a value of 4.3 6
with a majority of male patients (46 male vs 34 female). A 1.6 cm2 (P = .09). Six patients had singular defects; defects
significant number of patients were smokers (n = 16, were located at the patella in 3 cases, at the medial femoral
20.0%). In 80 patients, a total of 106 cartilage defects condyle in 2 cases, and in 1 case at the trochlear groove.
were treated with ACI-Cs, including 57 patients with a sin-
gle lesion, 22 patients with 2 lesions, and 1 patient with
more than 2 lesions. The mean defect size was 4.6 6 Probabilities for Constant or Improved Scores
1.7 cm2. Among those patients with isolated cartilage After 36 Months Follow-up
defects (n = 57), 23 patients suffered from defects located
To analyze if a time point could be estimated during our
on the medial femoral condyle (40.4%); in 22 cases, patellar
course of observation at which a steady state after ACI
defects were treated (38.6%); 8 defects were located on the
without further significant decreases or increases in sub-
lateral femoral condyle (14.0%); and in 4 patients, defects
jective scores was reached, the course of the patients indi-
of the trochlear groove were present (7.0%). In addition,
vidual IKDC and Lysholm scores was analyzed and
multiple defect locations were treated in 23 patients
assessed in relation to the scores obtained 36 months after
(28.8%). Detailed information on all patient characteristics
ACI. Not surprisingly, preoperative IKDC and Lysholm
is presented in Table 1.
scores were poor/fair. No patient had good or excellent
scores. A total of 35 (44.8%) of those cases failed to improve
Functional Clinical Outcomes as Assessed to good or excellent IKDC scores, whereas 41.3% of
by IKDC and Lysholm Scores patients maintained poor or fair Lysholm scores at the
end point of the study. Nearly half (46.6%) of the cases
A total of 83 patients were evaluated preoperatively. The with poor IKDC scores at 6 months after surgery did not
follow-up rate was 96.4%, with 80 patients evaluated at 6, improve to a higher score category when analyzed 36
12, 24, and 36 months after surgery by the IKDC and months after surgery. In 61.1% of all cases, patients with
Lysholm scores and included in this study according to the poor IKDC scores at 12 months after surgery still had
ICRS criteria at 36 months. Details of all scores can be found poor scores at 36 months after surgery. An improvement
in Tables 2 and 3 as well as Figure 1. In summary, a constant in IKDC scores between the time points of 24 and 36

Downloaded from ajs.sagepub.com by guest on April 8, 2016

Vol. 42, No. 1, 2014 Predicting Success or Failure of ACI at 36 Months 211

TABLE 2
Number of Patients in Each Category for IKDC and Lysholm Scores Preoperatively
and at 6, 12, 24, and 36 Months Postoperativelya

Preoperatively 6 mo 12 mo 24 mo 36 mo

IKDC score
Poor (\70) 79 (95.2) 58 (72.5) 36 (45.0) 26 (32.5) 28 (35.0)
Fair (71-80) 4 (4.8) 19 (23.8) 21 (26.3) 17 (21.3) 11 (13.8)
Good (81-90) 0 (0) 3 (3.8) 19 (23.8) 23 (28.8) 23 (28.8)
Excellent (.90) 0 (0) 0 (0) 4 (5.9) 14 (17.5) 18 (22.5)
Lysholm score
Poor (\65) 52 (62.7) 19 (23.8) 20 (25.0) 11 (13.8) 8 (10.0)
Fair (65-83) 31 (37.3) 50 (62.5) 25 (31.3) 28 (35.0) 25 (31.3)
Good (84-94) 0 (0) 11 (13.8) 30 (37.5) 27 (33.8) 24 (30.0)
Excellent (.95) 0 (0) 0 (0) 5 (6.3) 14 (17.5) 23 (28.8)

a
Data are given as n (%). IKDC, International Knee Documentation Committee.

TABLE 3
IKDC and Lysholm Scores Preoperatively and at 6, 12, 24, and 36 Months Postoperativelya

Preoperatively 6 mo 12 mo 24 mo 36 mo

No. of patients 83 80 80 80 80
Follow-up rate, % 100.0 96.4 96.4 96.4 96.4
IKDC scoreb 49.6 6 13.8 64.1 6 13.3 70.0 6 16.3 75.5 6 14.6 79.1 6 14.6
(16.1-75.3) (30.5-84.3) (19.3-97.7) (40.2-95.4) (50.4-97.3)
P value vs 36 mo \.001 \.001 \.001 \.001
Lysholm scoreb 59.5 6 11.6 70.6 6 12.9 76.0 6 16.6 81.3 6 14.2 83.5 6 13.7
(14.0-83.0) (31.0-94.0) (25.0-100.0) (36.0-100.0) (40.0-100.0)
P value vs 36 mo \.001 \.001 \.001 .020

a
Significant differences between various time points were calculated using the Wilcoxon signed-rank test to compare paired samples. Sig-
nificance level was P \ .05 for all analyses. IKDC, International Knee Documentation Committee.
b
Data are expressed as mean 6 standard deviation (range).

months was only observed in a minority of 19.2% of
patients. Detailed data on decreases or increases in
IKDC scores are presented in Table 4.
If patients already had good (81-90) and excellent (.90)
IKDC scores as early as 6 months after surgery, no
decrease in scores until the end point of this study at 36
months was found. A majority of patients (90.6%) with
good and excellent scores at 12 months showed constant
scores, whereas between 24 and 36 months, 82.6% of
patients had similar or improved scores at the time of
follow-up. Results obtained for the Lysholm scores over
the time course of this study showed similar trends as
observed for the IKDC scores (Table 4).
In summary, if scores were poor or fair at 6 months post-
operatively, only half the number of cases managed to further
improve their scores toward the end point of this study. If
poor or fair scores were still present at 12 and 24 months after
surgery, the majority of cases failed to further improve their
scores. Detailed results can be found in Table 4.
DISCUSSION
This study represents a prospective case series of 80 con-
secutive patients who were followed up to 36 months after
ACI for cartilage defects of the knee. Patients were evalu-
ated by means of the Lysholm and IKDC scores, which
have been validated for patients who have undergone car-
tilage repair and are recommended as appropriate outcome
parameters in these patients by the ICRS.5
Previous to ACI-Cs, matrix-associated ACI (MACI) had
been performed. In this procedure, chondrocytes are
seeded on a collagen membrane several days before sur-
gery. During the operation, the membrane is cut to size
and implanted into the defect area.1 However, at first
glance its easy application can be associated with a number
of disadvantages. Cell viability and the differentiation
state of the chondrocytes cannot be monitored after appli-
cation of the cells to the membrane. Additionally, cutting
an appropriate size and manipulation of the cell-seeded
membrane may result in a loss of chondrocytes or
decreased cell viability. Therefore, ACT-Cs was introduced
to combine the technical attractiveness of MACI with opti-
mal cell quality, easy handling, and easy application.
In the current study, ACI-Cs resulted in satisfying clin-
ical outcomes at 36 months follow-up, with a significant
increase in both IKDC and Lysholm scores from before sur-
gery. The failure rate was 12.5%, which is slightly higher
than in our previous analysis, where 5.9% of all patients
failed the procedure.20 Still, these results are in line with

Downloaded from ajs.sagepub.com by guest on April 8, 2016

212 Pestka et al The American Journal of Sports Medicine

A A
* 50
* * *
*
*
* 40
100

- IKDC
30
80
IKDC score (%)

20
60
10
40
0
20 MFC LFC Patella Trochlea

0 B
0 6 12 24 36
50 * * *
Follow up time (in months)
40 n. s.
B *
* - Lysholm
30
*
*
100 20
Lysholm score (points)

80 10

60
40
20
0 from preoperative to postoperative IKDC scores was
0 6 12
Follow up time (in months)
Figure 1. (A) A significant improvement in the International
Knee Documentation Committee (IKDC) score was observed
preoperatively as well as after 6, 12, and 24 months when
compared with 36 months follow-up. (B) Lysholm scores
constantly increased from preoperatively to 6, 12, and 24
months postoperatively and were significantly different from
scores at 36 months follow-up. *Significant differences
(P  .01) between individual time points.
0
MFC LFC Patella Trochlea
Figure 2. D International Knee Documentation Committee
(IKDC) and D Lysholm: mean differences between scores
before surgery and at 36 months after surgery with respect
to various defect locations. (A) The greatest improvement
24 36 observed for cases with defects located at the lateral femoral
condyle (LFC). These were significantly different (P \ .05)
when compared with other defect locations such as the
trochlea, patella, or medial femoral condyle (MFC). Compar-
ison between the MFC and patella or trochlea showed signif-
icant differences (P \ .05). Significant differences between
the defect locations at the trochlea and patella were addition-
ally found (P \ .05). (B) Analysis of D Lysholm similarly
revealed significant differences (all P \ .05) between all
locations analyzed with the exception of the trochlea
versus patella, where there was no statistical significance
(P = .13).

those of other studies in which failure rates were reported
to be as low as 7.7%, and 80% to 90% of patients reported
satisfying results postoperatively.8,17
Concerning the overall results of the present study, sig-
nificant improvements in knee function as measured by
the IKDC and Lysholm scores were found between 12
and 24 months after surgery as well as between 24 and
36 months after ACI. These findings are noteworthy, as
additional increases in knee function might be supported
by the certainty that ACI-Cs is a biological procedure in
which differentiation and maturation of regenerating car-
tilage last for a significant period of time. A possible expla-
nation for these clinical findings can be found in an
experimental cartilage study that was able to show that
after chondrocyte implantation, regenerated tissue under-
goes a process of maturation that in the majority of cases

Downloaded from ajs.sagepub.com by guest on April 8, 2016

Vol. 42, No. 1, 2014
TABLE 4
Probabilities of Constant IKDC and Lysholm Scores
at 36 Months in Relation to Clinical Results
at 6, 12, and 24 Months Postoperativelya
Probability at 36 mo
IKDC Score Lysholm Score
Poor/fair scores
Preoperatively 0.44 0.41
6 mo 0.51 0.46
12 mo 0.61 0.60
24 mo 0.81 0.77
Good/excellent scores
Preoperatively 0.00 0.00
6 mo 1.00 0.91
12 mo 0.91 0.83
24 mo 0.89 0.93
a
IKDC, International Knee Documentation Committee.
takes longer than 18 months to complete.4,22 During this
time, fibrous cartilage needs to be replaced by hyaline-
like tissue. Differentiation of cartilage replacement tissue
usually takes up to 24 months.22 After 5 years, complete
filling and integration of the graft as measured by mag-
netic resonance imaging (MRI) could be found in the major-
ity of patients.17 Here, good clinical function appeared to be
associated with sufficient knee function. With regard to the
assessment of clinical and subjective knee function after
complete cartilage differentiation, further improvement
in knee function has been observed for a short interval
between 24 and 36 months postoperatively.26,29 In addi-
tion, transplantation of articular chondrocytes has been
associated with good clinical short-term and midterm
results.
In contrast to patients with initial good and excellent
scores after ACI are those who reported poor and fair
scores as early as 6 months after surgery. Over the course
of the following 30 months, nearly 50% failed to improve
their knee function. This might distinguish the clinical
course of patients after ACI with the clinical course after
alternative techniques such as arthroscopic microfractur-
ing, which is generally recommended for smaller cartilage
defects measuring less than 2 to 4 cm2.19 Data obtained for
microfracturing show that clinical results seem to deterio-
rate between 24 and 36 months after surgery.19 In the cur-
rent study, the mean defect size measured 4.6 cm2, which
was well above the size recommended for microfracturing.
Inferior results have been reported for microfracturing in
defects of such a size.15 However, a total of 5 patients
(4.7%) had cartilage lesions smaller than 2 cm2. It is an
ongoing debate as to whether ACI is the best treatment
for these patients or if, in cases of failure, they are likely
to fail other cartilage regenerative treatments as well.
Interestingly, only 1 of those 5 patients with a single carti-
lage lesion of the medial femoral condyle reported a good
Lysholm score and excellent IKDC score at 36 months after
surgery. The remaining 4 patients all had cartilage lesions
in 2 locations, of which 3 patients showed poor or fair
Downloaded from ajs.sagepub.com by guest on April 8, 2016
Predicting Success or Failure of ACI at 36 Months 213
scores and only 1 patient showed a good score at 36 months
after surgery. Numerous individual factors such as age at
the time of implantation, sex, and defect origin, together
with general risk factors such as smoking and defect size,
have been identified that might possess an influence on
outcomes after cartilage repair.14,21,24 Additionally, it has
recently been reported that overweight and obesity are
negatively associated with satisfying results after ACI.12
However, no single factor can be associated with poor
clinical outcomes after cartilage regenerative surgery. It
therefore appears most likely that a combination of multi-
ple factors influences regeneration after ACI in general
and clinical outcomes in particular. However, as clinical
results of both the IKDC and Lysholm scores significantly
improved from 6 to 36 months after surgery, the ACI
procedure appears to be a success for the majority of
patients.
This is especially important as most patients wish to
receive information early after the operation regarding
general expectations toward success or failure. With the
help of this study, there may now be a possibility to discuss
such probabilities with the patient. It is therefore our gen-
eral recommendation to carefully assess and collect indi-
vidual scores at set intervals of 6, 12, 24, and 36 months.
In this context, it has been shown that clinical results after
this time appear to reach a plateau, with no significant fur-
ther changes either in knee function or patient satisfac-
tion.29 In addition, satisfactory results at 2 to 3 years
after ACI appear to be associated with good long-term
results.24,25 Therefore, from our point of view, the midterm
results up to 3 years after surgery presented in this study
can be used to appraise a first careful prognosis after ACI.
Of course, more extensive follow-up data such as 5-year
results will be necessary to provide further insight into
the clinical course after ACI-Cs and to allow solid
predictions.
On the basis of our data, patients with poor or fair
scores at 6 months after ACI might be informed that at
this early stage after surgery, chances of further improve-
ment in knee function and overall satisfaction can be esti-
mated at approximately 50%. For patients with good and
excellent scores at 6 months after surgery, on the other
hand, a significant deterioration in clinical results is
unlikely to occur over the course of the following 30
months. As the number of patients in this study with
good and excellent scores at 6 months after surgery was
low (n = 3) and as a 50% chance of improvement after ini-
tial poor ACI results resembles that of tossing a coin, it is
doubtful that such a discussion with the patient is profit-
able. It is therefore our recommendation to discuss the
chances of success or failure at 1 year after surgery at
the earliest. With respect to our data, giving a prognosis
at 1 year after surgery appears more reliable and less vari-
able. Most importantly, decision making regarding revi-
sion surgery should be postponed to 1 year after surgery
at the earliest.
Taken together, our overall recommendation is to dis-
cuss the individual chances of success or failure at 1 year
after surgery at the earliest. As early as 6 months after
surgery, patients with poor and fair scores show
214 Pestka et al
improvements, whereas the numbers of patients with good
and excellent scores are too low to give a reliable prognosis.
As early as 12 months or as late as 24 months after sur-
gery, this discussion can be much more goal oriented.
Concerning the limitations of this study, the lack of
a control group treated with a different technique and
the relatively short follow-up of only 36 months must be
considered. Therefore, only limited conclusions can be
drawn concerning the long-term outcomes of patients trea-
ted with ACI-Cs. This, however, we consider to be a general
limitation of most ACI studies in which few long-term
follow-ups are available. Unlike studies on implantation
in hip arthroplasty, for example, where follow-up data
average 7 years, ACI in general and ACI-Cs in particular
are relatively new techniques with consequently rather
limited follow-up times.23
An important general limitation of studies on cartilage
treatment, which can also be found in this study, is the
lack of objective assessments, such as MRI and histology.
Therefore, only subjective clinical results are presented.
It is certainly important to encourage the use of objective
outcomes, but as shown in this study, the use of the
IKDC and Lysholm scoring systems provides sufficient
data to predict the clinical course after ACI.
CONCLUSION
In conclusion, the 3-year prospective clinical follow-up data
of 80 consecutive patients after ACI-Cs show promising
results and a minimal failure rate. Timely sequential
data enabled us to compare clinical results at different
postoperative time points. Poor clinical findings (IKDC
\70) at 6 months postoperatively are associated with an
almost 50% chance of constant poor results. Patients
with good or excellent results (IKDC .81-100) at 6 months
after surgery generally maintain them, with a very high
probability (.80%) at 36 months after intervention. This
information can be beneficial for the treating physician
when taking care of postoperative ACI patients. As satisfy-
ing results after ACI can be predicted with a higher accu-
racy, they might be discussed earlier with the patient than
cases of suspected failure.
REFERENCES
1. Behrens P, Bitter T, Kurz B, Russlies M. Matrix-associated autolo-
gous chondrocyte transplantation/implantation (MACT/MACI): 5-
year follow-up. Knee. 2006;13:194-202.
2. Briggs KK, Steadman JR, Hay CJ, Hines SL. Lysholm score and
Tegner activity level in individuals with normal knees. Am J Sports
Med. 2009;37:898-901.
3. Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L.
Treatment of deep cartilage defects in the knee with autologous
chondrocyte transplantation. N Engl J Med. 1994;331:889-895.
4. Brun P, Dickinson SC, Zavan B, Cortivo R, Hollander AP, Abatangelo
G. Characteristics of repair tissue in second-look and third-look biop-
sies from patients treated with engineered cartilage: relationship to
symptomatology and time after implantation. Arthritis Res Ther.
2008;10:R132.
Downloaded from ajs.sagepub.com by guest on April 8, 2016
The American Journal of Sports Medicine
5. Collins NJ, Misra D, Felson DT, Crossley KM, Roos EM. Measures of
knee function: International Knee Documentation Committee (IKDC)
Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Out-
come Score (KOOS), Knee Injury and Osteoarthritis Outcome Score
Physical Function Short Form (KOOS-PS), Knee Outcome Survey
Activities of Daily Living Scale (KOS-ADL), Lysholm Knee Scoring
Scale, Oxford Knee Score (OKS), Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC), Activity Rating Scale
(ARS), and Tegner Activity Score (TAS). Arthritis Care Res (Hoboken).
2011;63 Suppl 11:S208-S228.
6. Erggelet C, Sittinger M, Lahm A. The arthroscopic implantation of
autologous chondrocytes for the treatment of full-thickness cartilage
defects of the knee joint. Arthroscopy. 2003;19:108-110.
7. Gooding CR, Bartlett W, Bentley G, Skinner JA, Carrington R, Flana-
gan A. A prospective, randomised study comparing two techniques
of autologous chondrocyte implantation for osteochondral defects
in the knee: periosteum covered versus type I/III collagen covered.
Knee. 2006;13:203-210.
8. Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan
DC. Failures, re-operations, and complications after autologous
chondrocyte implantation: a systematic review. Osteoarthritis Carti-
lage. 2011;19:779-791.
9. Hefti F, Muller W, Jakob RP, Staubli HU. Evaluation of knee ligament
injuries with the IKDC form. Knee Surg Sports Traumatol Arthrosc.
1993;1:226-234.
10. Henderson IJ, Tuy B, Connell D, Oakes B, Hettwer WH. Prospective
clinical study of autologous chondrocyte implantation and correlation
with MRI at three and 12 months. J Bone Joint Surg Br. 2003;
85:1060-1066.
11. Hirschmuller A, Baur H, Braun S, Kreuz PC, Sudkamp NP, Niemeyer
P. Rehabilitation after autologous chondrocyte implantation for iso-
lated cartilage defects of the knee. Am J Sports Med. 2011;
39:2686-2696.
12. Jaiswal PK, Bentley G, Carrington RW, Skinner JA, Briggs TW. The
adverse effect of elevated body mass index on outcome after autol-
ogous chondrocyte implantation. J Bone Joint Surg Br. 2012;
94:1377-1381.
13. Jones DG, Peterson L. Autologous chondrocyte implantation. J Bone
Joint Surg Am. 2006;88:2502-2520.
14. Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Sudkamp NP,
Niemeyer P. Autologous chondrocyte implantation for treatment of
cartilage defects of the knee: what predicts the need for reinterven-
tion? Am J Sports Med. 2012;40:58-67.
15. Knutsen G, Drogset JO, Engebretsen L, et al. A randomized trial
comparing autologous chondrocyte implantation with microfracture:
findings at five years. J Bone Joint Surg Am. 2007;89:2105-2112.
16. Lysholm J, Gillquist J. Evaluation of knee ligament surgery results
with special emphasis on use of a scoring scale. Am J Sports Med.
1982;10:150-154.
17. Marlovits S, Aldrian S, Wondrasch B, et al. Clinical and radiological
outcomes 5 years after matrix-induced autologous chondrocyte
implantation in patients with symptomatic, traumatic chondral
defects. Am J Sports Med. 2012;40:2273-2280.
18. McNickle AG, LHeureux DR, Yanke AB, Cole BJ. Outcomes of autol-
ogous chondrocyte implantation in a diverse patient population. Am
J Sports Med. 2009;37:1344-1350.
19. Mithoefer K, Williams RJ 3rd, Warren RF, et al. The microfracture
technique for the treatment of articular cartilage lesions in the
knee: a prospective cohort study. J Bone Joint Surg Am. 2005;
87:1911-1920.
20. Niemeyer P, Lenz P, Kreuz PC, et al. Chondrocyte-seeded type I/III
collagen membrane for autologous chondrocyte transplantation: pro-
spective 2-year results in patients with cartilage defects of the knee
joint. Arthroscopy. 2010;26:1074-1082.
21. Niemeyer P, Salzmann G, Steinwachs M, et al. Presence of subchon-
dral bone marrow edema at the time of treatment represents a nega-
tive prognostic factor for early outcome after autologous
chondrocyte implantation. Arch Orthop Trauma Surg. 2010;
130:977-983.
Vol. 42, No. 1, 2014 Predicting Success or Failure of ACI at 36 Months 215

22. Ossendorf C, Kaps C, Kreuz PC, Burmester GR, Sittinger M, Erggelet
C. Treatment of posttraumatic and focal osteoarthritic cartilage
defects of the knee with autologous polymer-based three-
dimensional chondrocyte grafts: 2-year clinical results. Arthritis Res
Ther. 2007;9:R41.
23. Perka C, Ludwig R, Stern S. [Total endoprosthetic management of
the hip joint after failed osteosynthesis of para-articular hip fracture].
Z Orthop Ihre Grenzgeb. 2000;138:39-45.
24. Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lin-
dahl A. Two- to 9-year outcome after autologous chondrocyte trans-
plantation of the knee. Clin Orthop Relat Res. 2000;374:212-234.
25. Peterson L, Vasiliadis HS, Brittberg M, Lindahl A. Autologous chon-
drocyte implantation: a long-term follow-up. Am J Sports Med.
2010;38:1117-1124.
26. Saris DB, Vanlauwe J, Victor J, et al. Characterized chondrocyte
implantation results in better structural repair when treating symp-
tomatic cartilage defects of the knee in a randomized controlled trial
versus microfracture. Am J Sports Med. 2008;36:235-246.
27. Steinwachs M. New technique for cell-seeded collagen-matrix-supported
autologous chondrocyte transplantation. Arthroscopy. 2009;25:208-211.
28. Steinwachs M, Peterson L, Bobic V, Verdonk P, Niemeyer P. Cell-
seeded collagen matrixsupported autologous chondrocyte trans-
plantation (ACT-CS): a consensus statement on surgical technique.
Cartilage. 2012;3:5-12.
29. Vanlauwe J, Saris DB, Victor J, Almqvist KF, Bellemans J, Luyten FP.
Five-year outcome of characterized chondrocyte implantation versus
microfracture for symptomatic cartilage defects of the knee: early
treatment matters. Am J Sports Med. 2011;39:2566-2574.

For reprints and permission queries, please visit SAGEs Web site at http://www.sagepub.com/journalsPermissions.nav

Downloaded from ajs.sagepub.com by guest on April 8, 2016