Orthopaedics & Traumatology: Surgery & Research 104 (2018) 695–700

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Original article / Work of the Orthopaedics and Traumatology Society of Western France (SOO)

Treatment of large deep osteochondritis lesions of the knee by

autologous matrix-induced chondrogenesis (AMIC): Preliminary
results in 13 patients夽
Pierre Bertho a , Adrien Pauvert b , Thomas Pouderoux c , Henri Robert b,∗ , the Orthopaedics
and Traumatology Society of Western France (SOO)d
a
Service d’orthopédie, CHU Pontchaillou, 2, rue Le Guilloux, 35033 Rennes, France
b
Service d’orthopédie, centre hospitalier Nord-Mayenne, 229, boulevard Paul-Lintier, 53100 Mayenne, France
c
Service d’orthopédie, CHU, 4, rue Larrey, 49100 Angers, France
d
Société d’orthopédie de l’ouest (SOO), 18, rue de Bellinière, 49800 Trélazé, France

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

Article history: Background: Osteochondral defects due to advanced osteochondritis of the knee eventually cause
Received 26 January 2018 osteoarthritis. Autologous matrix-induced chondrogenesis (AMIC) may hold potential for overcoming
Accepted 17 May 2018 the treatment challenges raised by defects larger than 2 cm2 . The primary objective of this study was to
assess medium-term functional outcomes of AMIC. The secondary objective was to confirm the absence
Keywords: of adverse events.
Knee Hypothesis: AMIC significantly improves knee function in patients with osteochondritis responsible for
Osteochondritis
osteochondral defects grade III or IV in the International Cartilage Repair Society (ICRS) classification.
Autologous matrix-induced chondrogenesis
Chondro-Gide
® Material and methods: A total of 13 consecutive patients managed using AMIC between September 2011
Microfracture and November 2016 were included in a prospective, single-centre, single-surgeon study. There were 8
males and 5 females with a mean age of 29 years (range, 15–51 years). Among them, 9 had had previous
surgery. The ICRS grade was IV in 12 patients and III in 1 patient. The defects had a mean surface area of
3.7 cm2 (range, 2.2–6.9 cm2 ) and mean depth of 0.5 mm (range, 0.4–0.8). In each patient, knee function
was assessed by an independent examiner based on validated instruments (Knee injury and Osteoarthritis
Outcome Score [KOOS], subjective International Knee Documentation Committee [IKDC] score, and visual
analogue scale [VAS] pain score).
Results: After a median follow-up of 24 months (range, 12–42 months; minimum, 1 year), 11 patients
had significant improvements, with mean increases in the IKDC score and KOOS of 27 and 28 points,
respectively. The scores remained stable after the first year. Of the 2 patients with poorer outcomes, 1
had a history of multiple surgical procedures and the other was a 51-year-old female with a defect surface
area of 6.9 cm2 . No post-operative complications were recorded.
Conclusion: AMIC is a reliable single-stage method that is both reproducible and widely available. AMIC
significantly improves knee function scores in patients with large osteochondral defects due to advanced
osteochondritis of the knee.
Level of evidence: IV, prospective cohort study.
© 2018 Published by Elsevier Masson SAS.

1. Introduction

The treatment of extensive osteochondral defects of the knee

due to advanced osteochondritis dissecans (OCD) is challenging
and controversial [1,2]. The simultaneous loss of bone and car-
tilage complicates the repair process, precluding the isolated use
夽 Article issued from the Orthopedics and Traumatology Society of Western France
of bone marrow-stimulation techniques. For defects with surface
(SOO) – 2017 Tours meeting.
∗ Corresponding author. areas of less than 2 cm2 , mosaic osteochondral grafting produces
E-mail address: henri.robert@wanadoo.fr (H. Robert). good outcomes [3–5]. Defects larger than 2 cm2 , in contrast, require

https://doi.org/10.1016/j.otsr.2018.05.008
1877-0568/© 2018 Published by Elsevier Masson SAS.
696 P. Bertho et al. / Orthopaedics & Traumatology: Surgery & Research 104 (2018) 695–700
complex and expensive techniques such as third-generation autol-
ogous chondrocyte grafting or fresh autologous osteochondral
grafting [6–10]. An appealing technique for large, deep defects
is autologous matrix-induced chondrogenesis (AMIC), which was
developed based on work by Gille et al. [11,12] and first described
by Behrens in 2005 [13]. This single-stage treatment is affordable
and available in France. It involves microfracturing the osteochon-
dral lesion, filling the defect with autologous cancellous bone and,
finally, suturing or gluing a membrane made of natural collagen
over the defect [13]. Thus, AMIC combines microfractures and
coverage of the defect with a collagen matrix to treat the osteochon-
dral lesion. After microfracturing, mesenchymal stem cells migrate
into the fibrin clot. However, the fibro-cartilaginous repair tissue,
thus produced cannot withstand the compression and shear forces
applied to the joint. The collagen matrix stabilises the fibrin clot and
creates a micro-environment conducive to stem-cell metaplasia
(‘biological chamber’) [14].
The primary objective of this study was to assess medium-term
functional outcomes of AMIC therapy. The secondary objective was
to confirm the absence of adverse events. The working hypothesis
was that AMIC significantly improves knee function in patients with
OCD responsible for osteochondral defects grade III or IV in the
International Cartilage Repair Society (ICRS) classification.
2. Material and method
2.1. Population
The 18 consecutive patients treated between September 2011
and November 2016 were included in a single-centre, single-
surgeon (HR), prospective study (Table 1). All patients who had OCD
responsible for defects seen by magnetic resonance imaging (MRI)
to be larger than 2 cm2 and grade III or IV in the ICRS classifica-
tion were included. Exclusion criteria were osteochondral fracture,
OCD with joint line narrowing (Ahlbäck grade 1), defect smaller
than 2 cm2 , juvenile OCD, isolated cartilage defect, inflammatory
disease, avascular necrosis, and follow-up shorter than 1 year. Five
patients were excluded, for follow-up shorter than 1 year (n = 3)
or for simultaneous femoral osteotomy to correct valgus defor-
mity > 5◦ on the long-leg radiograph (n = 2). This left 13 patients
for the study, 8 males and 5 females, with a mean age of 29 years
(range, 15–51 years). There were 7 right and 6 left knees. The medial
condyle was involved in 8 patients, lateral condyle in 4 patients,
and patella in 1 patient. Mean defect surface area measured intra-
operatively was 3.7 cm2 (range, 2.2–6.9 cm2 ) and mean depth was
0.5 cm (range, 0.4–0.8 cm). Of the 13 defects, 12 were ICRS grade IV;
the remaining defect was a condylar stage III lesion with an in situ
sequestrum pedicled on the synovium of the notch. Nine patients
had a history of OCD surgery consisting in removal of osteochondral
fragments (n = 6) or screw fixation of fragments (n = 3). All patients
gave written informed consent to study participation including,
regular post-operative follow-up visits.
2.2. Operative technique
The first step was arthroscopic freshening of the bed of the defect
down to compact epiphyseal bone and resection of any unstable
edges. A graduated hook was then used to measure the width,
height, and depth of the lesion. Multiple drill holes were then cre-
ated using a bit 1.5 to 2 mm in diameter, down to 20 mm, until blood
issued from each orifice (Fig. 1a–c). A minimally invasive arthro-
tomy was performed for the second step. Cancellous bone grafts
were placed within the defect to restore the native convexity of
®
the femoral condyle. The collagen matrix (Chondro-Gide , Geistlich
Pharma, Wolhusen, Switzerland) was stitched using braided suture
(Vicryl 5.0) applied onto the peripheral healthy cartilage (Fig. 1d).
In a minority of cases, the sutures were reinforced with biologi-
®
cal glue (Tissucol , Baxter, Vienna, Austria). In the patient with a
patellar defect, all the steps of the procedure were performed on
the everted patella, through an arthrotomy incision.
2.3. Post-operative care
Mobilisation of the knee was unrestricted, increasing gradually
from 0◦ to 90◦ , with no splint. Limited weight bearing (10–15 kg)
was encouraged during the first month, followed by a gradual tran-
sition to full weight bearing. The patient with a patellar defect wore
a splint that limited flexion at 30◦ for 1 month, but was allowed to
bear full weight immediately after the procedure.
2.4. Assessment methods
All 13 patients were evaluated prospectively by an independent
examiner before surgery, then 1 year later and at last follow-
up. The evaluations consisted in determining the Knee injury
and Osteoarthritis Outcome Score (KOOS), subjective International
Knee Documentation Committee (IKDC) score, and visual analogue
scale (VAS) pain score. Patients were asked whether they would
have the procedure again.
2.5. Statistical analysis
Wilcoxon’s test for paired samples was applied to assess differ-
ences in functional scores between the pre-operative value and the
values after 1 year and at last follow-up. Values of p lower than 0.05
were taken to indicate significant differences.
3. Results
Median follow-up was 24 months (range, 12–42 months). No
patient was lost to follow-up.
3.1. Complications
There were no cases of infection, deep vein thrombosis, or
procedure-specific complications (membrane avulsion, inflamma-
tory response). No patient underwent subsequent treatment with
a different cartilage repair technique or joint replacement.
3.2. Functional outcomes
The median IKDC score improved from 46 to 74 and the median
KOOS from 51 to 77. The VAS pain score, IKDC score and KOOS
improved significantly between the pre-operative visit and the 1-
year post-operative visit then remained stable, with no further
changes at last follow-up (Fig. 2). Thus, the 1-year gains were sus-
tained over time.
Of the 13 patients, 11 were satisfied with the procedure. The
remaining 2 patients had insufficient outcomes. Among them,
patient #13 with a defect in the medial condyle had a history of
screw fixation, removal of the material and third-generation chon-
drocyte grafting before the AMIC procedure. The functional scores
did not improve. By MRI after 14 months, the cartilage was con-
tinuous but the subchondral cancellous bone graft had a patchy
appearance. The other patient (#9) was a 51-year-old female who
had a 2-year history of symptoms from a medial condylar defect
with a surface area of 6.9 cm2 . After 18 months, she had persistent
pain (VAS score of 5/10) and no improvements in the IKDC score or
KOOS. MRI performed after 14 months showed no tissue filling the
defect.
Table 1
Demographics, surgical data, and outcomes.

P. Bertho et al. / Orthopaedics & Traumatology: Surgery & Research 104 (2018) 695–700
No. Patient DOB dd/mm/yyyy Location Side Previous surgery Date of AMIC Age at Surface Pre-op. 1-year FU Max FU
AMIC, y area cm2

VAS pain IKDC score KOOS VAS pain IKDC score KOOS (Months) VAS pain IKDC score KOOS

1 1 4/23/1973 Med. condyle R Fragment excision 5/22/2012 38 3.4 8 52 68 1 84 95 42 1 98 92

debridement
2 2 12/17/1984 Med. condyle L Fragment excision 10/29/2013 29 2.3 4 46 47 2 62 91 30 1 83 83
3 3 12/4/1991 Lat. condyle R Fragment excision 12/3/2016 25 3 5 55 60 3 65 71 26 3 65 71
cancellous graft
4 4 9/27/1979 Med. condyle R Screw fixation 12/20/2013 34 4.2 8 63 49 2 81 84 24 1 80 93
5 5 1/31/1998 Lat. condyle R Screw fixation 7/3/2013 15 2.2 6 45 57 0 72 83 30 6 70 71
6 6 6/27/1994 Med. condyle L No 11/7/2012 18 3 4 55 56 0 88 95 42 0 99 99
7 7 7/24/1992 Lat. condyle R No 10/2/2014 22 6 3 75 71 2 82 83 24 3 88 86
8 8 9/20/1977 Lat. condyle L No 11/16/2016 39 3.7 4 39 51 3 74 90 15 2 74 92
9 9 4/1/1965 Med. condyle R Fragment excision 1/26/2016 51 6.9 6 41 31 4 49 58 18 4 44 56
10 10 3/18/1977 Med. condyle L No 2/23/2016 39 1.8 7 33 34 3 76 66 24 3 74 58
11 11 2/22/1989 Patella L Fragment excision 6/7/2016 27 2.9 8 34 41 2 75 77 18 3 70 77
12 12 9/28/1997 Med. condyle L Flap suture 4/26/2016 19 3.5 5 62 73 3 69 67 20 2 71 67
Fragment excision
13 13 6/17/1988 Med. condyle L Screw fixation 7/19/2016 28 5.7 4 29 31 7 29 38 17 6 41 40
Chondrocyte graft
Age at AMIC, y Surface area cm2 Pre-op. 1-year FU Max FU

VAS pain IKDC score KOOS VAS pain IKDC score KOOS (Months) VAS pain IKDC score KOOS

Mean 29.5 3.7 5.5 48 51 2.5 70 77 25 2.7 74 76

SD 10 1.6 1.8 13 14 1.8 16 16 8 2 17 17
Median 28 3.5 5 46 51 2 72 83 24 3 74 75

The rows in italics provide the data for the 2 patients with unsatisfactory outcomes.

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698 P. Bertho et al. / Orthopaedics & Traumatology: Surgery & Research 104 (2018) 695–700
Fig. 1. a: large OCD defect in the medial condyle (patient #7); b: micro-drilling is performed after debridement of the lesion to subchondral bone; c: the entire defect is filled
with a cancellous bone graft; d: the collagen membrane is stitched to the edges of the defect using Vicryl 5.0 suture.
Fig. 2. Changes in the mean IKDC and VAS pain scores after 1 year and at last follow-
up.
All 13 patients stated that they would be willing to have the
same procedure again.
4. Discussion
4.1. Outcomes
This clinical study demonstrated functional benefits from an
osteochondral repair technique used to treat large deep defects due
to OCD. Of 13 patients, 11 experienced significant improvements
with mean gains of 27 and 28 points on the IKDC score and KOOS,
respectively, 1 year after the procedure (Table 2). These findings
validate the working hypothesis that AMIC produces functional
gains. The presence or absence of improvements after 1 year is
sustained over time. The 11 improved patients were satisfied with
the procedure and all 13 patients were willing to have the proce-
dure again. The AMIC registry data reported by Gille et al. indicate a
longer period of improvement extending over the first 2 years after
the procedure [15].
A 2010 report about 27 patients assessed by Gille et al., 5 years
after AMIC found no influence on clinical outcomes of age, gen-
der, body mass index, or previous OCD surgery [16]. In contrast, a
grafted surface area greater than 8 cm2 was associated with poor
outcomes. None of our patients had a grafted surface area greater
than 7 cm2 .
Kusano et al. reported that AMIC provided better outcomes in
patients with OCD compared to those with traumatic defects [17].
The better outcomes in OCD may be related to the concomitant use
of cancellous bone grafts and more favourable natural history of
OCD.
The 1-year and 2-year outcomes in the first randomised con-
trolled trial of AMIC versus isolated microfractures were reported
by Anders et al. [18]. After a longer follow-up of 5 years, the scores
had decreased significantly in the microfracture-only group and
remained unchanged in the AMIC group [19]. The better outcomes
in the AMIC group seemed related to more complete filling of the
osteochondral defects [19]. The randomised trial had two AMIC
®
arms, with suture and glue fixation of the Chondro-Gide mem-
brane, respectively, between which no significant differences were
found [18].
In a study by Schiavone Panni et al. of 21 patients with defects
larger than 2 cm2 , the clinical benefits of AMIC therapy were sus-
tained over the mean follow-up of 7 years (range, 6.5–8 years)
[20].
4.2. Operative technique
The technique involving multiple perforations with an awl
developed by Steadman has been superseded by drilling, based
 P. Bertho et al. / Orthopaedics & Traumatology: Surgery & Research 104 (2018) 695–700 699

Table 2
Published data on AMIC.

Author Year Sample Age years ICRS Surface FU months VAS pain score Lysholm score IKDC score
size grade area cm2

Pre-op. Post-op. Pre-op. Post-op. Pre-op. Post-op.

Gille J [15] 2013 57 37.3 III 3.4 24 7 ± 1.8 2 ± 2.1 50 ± 19.6 85.2 ± 18.4 / /
Kusano T [17] 2012 11 25.9 ± 3 IV 4 ± 0.4 27 ± 2.3 6±3 1±1 50 ± 25 94 ± 8 44 ± 25 88 ± 9
Volz M [19] 2017 34 37 ± 10 III and IV 3.8 ± 2 60 54 ± 19 1.5 ± 1 45 ± 19 85 ± 9
Schiavone Panni [20] 2017 21 35 III 4.3 78 to 96 / / 38.8 ± 12.4 72.6 ± 19.5 31.7 ± 8.9 80.6 ± 5.3
Notre série 2018 13 29.5 ± 10 IV 3.7 ± 1.6 25 ± 8 5.5 ± 1.8 2.7 ± 2 / / 48 ± 13 74 ± 17

on work by Chen et al. [21]. The need for an arthrotomy incision affordable. Further studies are needed to confirm these preliminary
to suture the collagen membrane may constitute a drawback. An findings.
arthroscopic technique in which the membrane is glued in place has
been reported to ease the post-operative course without affecting Disclosure of interest
long-term outcomes [22,23]. We have no experience with the other
®
available acellular membranes (MaioRegen , Finceramica. Faenza. The authors B.P., P.A., and P.T. declare that they have no com-
® ®
Italy; Chondrotissue , BioTissue, Doral, FL, USA; Hyalofast , Anika peting interest.
Therapeutics, Bedford, MA, USA). H.R. is a consultant for Geistlich, F.H. and Genourob, and holds
Several changes to the original AMIC technique have been sug- shares in Genourob..
gested. Dhollander combined AMIC with platelet-rich plasma gel
injected under the membrane before completing the suture [24].
Funding sources

4.3. Indication None.

Findings from several studies fully support the use of osteo-

chondral repair techniques to treat deep symptomatic defects [3,4].
Sanders et al. reported 2-fold and 3-fold increases in the risk of
osteoarthritis and arthroplasty, respectively, after osteochondral
fragment excision compared to defect filling [25]. ICRS grade III
osteochondral defects should be treated with combined fixation
and mosaicplasty [26] and symptomatic, deep, grade IV defects
measuring less than 2 cm2 with mosaicplasty [5]. Microfracture
therapy is not indicated in patients with deep defects larger than
2 cm2 . Third-generation chondrocyte grafting, in which the cells
are embedded in a matrix, may deserve consideration based on
good reported outcomes in OCD [27] but is losing ground in Europe
and virtually unavailable in France [28]. Osteochondral allograft-
ing is popular in the USA but cannot be performed in France [7].
At present, AMIC is a reliable and simple option for treating these
defects. However, AMIC is not indicated in patients with defects
larger than 8 cm2 [15].
Lower limb malalignment is among the causes of AMIC failure.
In patients with more than 4◦ or 5◦ of valgus or varus, normal align-
ment or slight overcorrection should be obtained [9]. To this end, an
osteotomy can be performed during the same procedure as AMIC.
Patellar malalignment requires a medialisation osteotomy of the
anterior tibial tuberosity.
4.4. Strengths and limitations of the study
This single-centre and single-surgeon study included consecu-
tive patients, none of whom was lost to follow-up. All patients had
deep, ICRS grade III or IV, large defects in a condyle or the patella.
The study was preliminary with only 13 patients. The minimum
follow-up was only 12 months. The full measure of improvement
seemed to be obtained within 1 year, with no change subsequently.
There was no control group, but no published studies have com-
pared AMIC to repair techniques other than microfractures [18].
5. Conclusion
The use of an acellular matrix to cover a microfracture site pro-
duces good outcomes in patients with focal, large, deep defects
due to advanced OCD. This one-stage technique is both reliable and
Contributions of each author
P.B. and H.R. wrote the article.
P.A. and P.T. re-evaluated the patients.
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