0363-5465/98/2626-0853$02.

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THE AMERICAN JOURNAL OF SPORTS MEDICINE, Vol. 26, No. 6
© 1998 American Orthopaedic Society for Sports Medicine

Current Concepts
Articular Cartilage Lesions of the Knee
Bert R. Mandelbaum,*† MD, Jon E. Browne,‡ MD, Freddie Fu,§ MD, Lyle Micheli,i MD,
J. Bruce Mosely, Jr.,a MD, Christoph Erggelet,b MD, PhD, Tom Minas,c MD, and
Lars Peterson,d MD

From *Santa Monica Orthopaedic and Sports Medicine Group, Santa Monica, California;
‡University of Missouri at Kansas City and University of Kansas, Shawnee Mission, Kansas;
§Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania;
iDivision of Sports Medicine, Children’s Hospital, Boston, Massachusetts; aBaylor Sports
Medicine Group, Houston, Texas; bOrthopaedische Universitaetsklinik, Freiburg, Germany;
c
Brigham Orthopedic Association, Boston, Massachusetts; and dGothenburg Medical Center,
Vastra Frolunda, Sweden

Hunter in 174318 described ulcerations of articular carti-
lage as problems that will not heal. The clinical conse-
quences of full-thickness articular cartilage defects of the
knee are pain, swelling, mechanical symptoms, athletic
and functional disability, and osteoarthritis (Fig. 1). Full-
thickness articular cartilage defects have an inherently
poor capacity for intrinsic repair, despite a plethora of
historical concepts, procedures, and techniques that have
been developed to meet this challenge. Meeting the chal-
lenge of complete restoration of the articular surface after
a defect is analogous to meeting the challenge of man
reaching the surface of the moon. It took the leadership
and vision of President John F. Kennedy in 1961 to de-
velop a systematic approach to space flight that culmi-
nated in the reality of the Mercury, Gemini, and Apollo
projects. It was this systematic, sequential progression
that attained Neal Armstrong’s “small step for man, but a
giant leap for mankind” on July 20, 1969. The challenge to
restore the articular surface is a multidimensional chal-
lenge for those working in the basic science laboratory and
in the operating room. The purpose of this article is to
present the current concepts with respect to the articular
cartilage defect, the histologic, biochemical, and clinical
implications, and the contemporary treatments from a
historical and an evolutionary prospective.
† Address correspondence and reprint requests to Bert Mandelbaum, MD,
Santa Monica Orthopaedic and Sports Medicine Group, 1301 Twentieth
Street, Suite 150, Santa Monica, CA 90404.
No author or related institution has received financial benefit from research
in this study.
STRUCTURE AND FUNCTION OF ARTICULAR
CARTILAGE
The principal function of articular cartilage, as a vis-
coelastic material, is variable loadbearing through a range
of motion and in functional activities. This function de-
pends on the specific composition and organization of this
composite structure6 (Fig. 2). An essential role of articular
cartilage is to reduce stress on subchondral bone and to
minimize friction. Normal articular cartilage is composed
of matrix, cells or chondrocytes, and water; it is contiguous
with and overlies the subchondral bone. The matrix is
principally composed of type II collagen fibers, but types
V, VI, IX, X, and XI collagen are present in smaller
amounts. Sulfated proteoglycans are linked to hyaluro-
nate. It is this lattice-type framework, in conjunction with
the collagen fibrils, that is responsible for the structural
properties of articular cartilage, including its tensile
strength and resiliency.6 Other components include bigly-
can, decorin, fibromodulin, fibronectin, lipids, and link
proteins. The chondrocyte is of mesenchymal stem cell
origin and is primarily responsible for synthesizing the
matrix. The range of water composition varies from 65% to
80%, depending on the load status and the presence or
absence of degenerative changes.6 The layers of the “func-
tional organization unit” include the tangential zone, in-
termediate zone, calcified cartilage, the tidemark, and the
subchondral bone (Fig. 3). This is very complex and spe-
cific with respect to morphology, biochemical, composition,
and biomechanical structural and material properties.
Uninjured cartilage has optimal resilience and loadbear-
ing characteristics.
With full-thickness articular cartilage injury, a healing

853
854 Mandelbaum et al.
Figure 1. Full-thickness, grade IV articular cartilage defect
in the medial femoral condyle.
Figure 2. The lattice-like composition of articular cartilage.
response is initiated with hematoma, stem cell migration,
and vascular ingrowth.6 This stereotypical response usu-
ally produces type I collagen and resultant fibrous carti-
lage rather than the preferred hyaline cartilage as pro-
duced by the chondrocyte.12 This “repair cartilage” has
diminished resilience and stiffness, poor wear character-
istics, and the predilection for the development of
osteoarthritis.
The challenge for the orthopaedic surgeon and the basic
scientist, therefore, is to facilitate the chondrocyte func-
tion, the role of growth factors, and the production and
survival of new matrix that approaches the biomechanical
and structural characteristics of hyaline cartilage.
In the patient with an injured ACL, there appears to be
a close relationship between ligament injury and articular
cartilage deterioration. In a study of ACL injuries, Loh-
mander27 demonstrated a consistent rapid elevation of the
metalloproteinase enzyme stromelysin and other cyto-
kines7 that cleave articular cartilage. Subchondral bone
bruises, found most commonly in the lateral compart-
ment, were present in approximately 80% of the ACL
American Journal of Sports Medicine
Figure 3. Organization of the articular cartilage unit showing
the four layers described in the text. (Reproduced with per-
mission from Minas and Nehrer.34)
injuries studied with MRI.23, 33, 35 These studies illumi-
nate the biochemical and mechanical complexities with
respect to the cause and the long-term natural history,
resulting in articular degeneration. This relationship is
most evident in a 9-year data registry of Johnson (person-
al communication, 1997). In his study of a population with
ACL injuries, he found accompanying articular cartilage
defects at an incidence of 1.9% for acute injuries, but an
overall incidence of 19% over this time period. These and
other studies suggest that acute ACL injury with disrup-
tion of the osteochondral functional unit and an unstable
ligament environment unleashes a destructive biochemi-
cal process that may result in a progressive deterioration
of its articular cartilage.7, 27, 47
THE HISTORICAL EVOLUTION OF CARTILAGE
REPAIR OPTIONS
Historically, the first attempted articular cartilage repairs
employed procedures including lavage, debridement, dril-
ling, and microfracture to stimulate mesenchymal stem
cell metaplasia to form fibrocartilage. More recently, sub-
stitution replacement techniques using allografts and au-
tografts have been successfully applied to defects in artic-
ular cartilage. Most recently introduced have been biologic
replacement techniques using autologous chondrocyte cell
culture technology.
Mesenchymal Stem Cell Stimulation
The first group of procedures for articular cartilage repair
were the mesenchymal stem cell stimulation techniques.
The 1946 Magnusson30 article on debridement resulted in
a sequence of approaches to this dilemma for repair. In
1948 Smith-Peterson49 introduced the “mould arthro-
plasty” in his attempt to regenerate the hip joint surface.
In 1979 Ficat et al.11 introduced the concepts of spongial-
ization and production of repair cartilage in response to
debridement. Reports on open arthrotomy drilling by Pri-
die in 195941 and Insall in 197419 were the next proce-
dures in this sequence. The introduction of the arthro-
Vol. 26, No. 6, 1998 Articular Cartilage Lesions of the Knee 855

scope facilitated the development of a variety of drilling with fibrocartilage. Outerbridge et al. in 199539 reported
and microfracture procedures including those by Sprague clinical improvements in 10 patients with lateral patellar
in 1981,50 Ogilvie-Harris and Jackson in 1984,38 Schon- autografts. In 1993, Matsusue et al.31 published a case
holtz and Ling in 1985,46 Rae and Noble in 198942 for report of a patient who had a successful ACL reconstruc-
osteochondral lesions, and Rodrigo et al. in 1994,44 who tion that used a mosaicplasty autograft replacement as
used the “ice pick” microfracture procedure. Rodrigo et al. initially described by Yamashita et al.53 A subsequent
also corroborated the thesis of Salter et al.45 that contin- report by Bobic3 describes “good and favorable results,
uous passive motion is useful in the postoperative period with promising uniform results in 10/12 patients” without
of cartilage repair procedures. In the study by Rodrigo et comprehensive outcome efficacy and safety data in small
al., continuous passive motion45 was used 6 hours a day lesions less than 2 cm2. In an unpublished comparative
for an 8-week period after arthroscopic microfracture; this study done in 1997, Hangody demonstrated that at 5
resulted in a statistically significant improved clinical re- years, mosaicplasty had superior postoperative outcome
sult. The limitation of this study is that it does not assess scores, determined by the Cincinnati and Hospital for
the histologic or functional outcome of the repaired carti- Special Surgery rating scales, when compared with abra-
lage, but it stresses the importance of rehabilitation tech- sion arthroplasty, microfracture, and Pridie drilling for
nique and protocol after surgical intervention. repair of articular cartilage lesions from 1 to 9 cm2 (Fig. 4).
Abrasion arthroplasty as introduced by Johnson in The mosaicplasty group lesions averaged 3.3 cm2 and
198624 initially appeared promising, but clinical results ranged up to 4.1 cm2 compared with those found in the
with this method have deteriorated over time. Jackson et microfracture group. This study concludes that the results
al. in 198822 and Jackson21 demonstrated initial improve- of the mesenchymal procedure deteriorate over time, with
ment with lavage and arthroscopic debridement, but these
results also diminished over time. Overall, debridement,
drilling, and the microfracture and abrasion techniques
repair the articular cartilage defect with fibrocartilage.
This principally is type I collagen and, rarely, types II, VI,
and IX that are found with a more hyaline cartilage type
of repair.6 It is now well known that the mesenchymal
stem cell derived from bone marrow can differentiate
along a chondrogenic lineage. This has been demonstrated
in vitro and in vivo as the process of the differentiation is
modulated by growth factors such as transforming growth
factor (TGF-b).1, 25
It appears that these clinical results deteriorate over
time because of the poor wear characteristics. These ob-
servations resulted in the evolution of “substitution re-
placement” and “cell transplantation” options.

Substitution Replacement Options

Repair of osteochondral defects by segmental replacement

with fresh allografts was first introduced by Lexer in
1908.26 In a study of segmental allograft replacement for
large traumatic articular cartilage defects, McDermott et
al.32 reported good or excellent results in 75% and 64% of
their patients at 5 and 10 years, respectively. Convery et
al.,9 using allografts for smaller defects, found a 76%
overall improvement and demonstrated that the medial
femoral condyle had 86% good or excellent results as com-
pared with 56% good or excellent results for the bipolar
lesions. Although these results have stood the test of time,
the logistical problems of tissue procurement by using
fresh, unirradiated osteochondral grafts coupled with the
potential for disease transmission have limited the wide-
spread application of these techniques.
Recently, autograft substitution replacements have be- Figure 4. Technique of Hangody’s mosaicplasty technique.
come popular for small, 1- to 2-cm, lesions. This clinically This is a schematic that demonstrates the six steps: 1, prep-
is referred to as “mosaicplasty.” Initially in a dog model, aration of donor site; 2–5, the procurement and placement of
Hangody14 has reported on osteochondral plug repair of donor graft and transplantation of osteochondral graft; and 6,
articular cartilage defects demonstrating survival of the the final result, showing the osteochondral grafts in the re-
osteohyaline cartilage plug while the interstices are filled cipient defect.
856 Mandelbaum et al.
improvements ranging from 48% to 62% at 5 years,
whereas results of mosaicplasty stabilize with 86% to 90%
good results.15 In 1997 Hangody15 also published a pre-
liminary report of 44 patients who had undergone arthro-
scopic mosaicplasty. Half of these procedures were per-
formed as a primary option and there were no data on the
size of the lesions. The results revealed Hospital for Spe-
cial Surgery score improvements from 62 preoperatively
to 94 postoperatively. The only complications were three
postoperative hematomas that gradually resolved.
These early results are encouraging, but long-term out-
come data are necessary to confirm initial impressions. In
1995 Takahashi et al.,52 using rabbit iliac callo-osseous
grafts, found that hyaline cartilage could be generated.
Stone in 199751 reported on 21 patients who had a micro-
fracture procedure with a “slurry osteoarticular graft”
without any method of graft fixation. The procedure was
followed by a 6-week continuous passive motion program
with favorable results; there are no long-term follow-up or
any outcome data to date.
Cell/Biologic Replacement Options
Skoog and Johansson in 197648 and Homminga et al. in
199016 used perichondrium as a replacement option for
repairing articular cartilage defects, thinking that this
would stimulate production of hyaline cartilage. Unfortu-
nately, perichondrium replacement resulted in the pro-
duction of collagen type X and endochondral ossification in
about two-thirds of the population (20 of 30 patients) at
5-year follow-up. O’Driscoll et al. in 198837 introduced a
technique using a young rabbit model and periosteum
transplantation with continuous passive motion; they
demonstrated promising quantitative and qualitative re-
pair of articular cartilage defects. Unfortunately, clinical
results presented in 1997 (S. W. O’Driscoll, unpublished
data) of adult rabbits with articular lesions were not good.
In 1997, Lorentzon28 reported on 25 patients who used
continuous passive motion followed by active motion and
progressive strength training after having only perios-
teum replacement for patellar full-thickness defects (area
range, 0.75 to 20 cm2). The mean age of the patients was
31.4 years (range 19 to 52) at the time of surgery. The
cause of the defect was chondromalacia in 11 patients,
osteochondral fracture in 3, patellar dislocation in 3, and
patellar contusion in 8 patients. He reported 16 excellent
and 9 good results at 42 months. Twelve of his 25 patients
(48%) returned to their previous levels of competitive
sport, and Lorentzon recommended this option for pa-
tients with disabling patellofemoral pain.
Grande et al. in 1989,13 using a rabbit model, demon-
strated a significantly different and a more complete re-
pair of articular defects when periosteal transplants were
supplemented with cultured chondrocytes. The rationale
for this procedure is based on the ability of normal artic-
ular chondrocytes that are released enzymatically to de-
differentiate in monolayer culture and undergo prolifera-
tive expansion.2 This expansion provides a large number
of cells that are transplanted into a large articular carti-
lage defect; the cells are covered by a periosteal flap where
American Journal of Sports Medicine
they redifferentiate and make hyaline-like cartilage.
These results were corroborated by Brittberg et al. in
19965 when they reported that articular defects in rabbits
treated with periosteum-plus-cultured chondrocytes dem-
onstrated significantly enhanced repair when compared
with those treated with periosteum alone (Fig. 5). The
clinical study by Brittberg et al.4 that was published in the
New England Journal of Medicine in 1994, although lim-
ited in numbers (23 patients) and follow-up (2 years),
revealed early encouraging results of this technique. In
this series, 14 of 16 (87%) femoral condyle lesions that
were implanted with autologous cultured chondrocytes
yielded good or excellent results. Repair of patellar de-
fects, however, was not as satisfactory.
Peterson in 1997 (unpublished data) reported a study of
articular cartilage lesions with comprehensive clinical,
biomechanical, and histologic follow-up. One hundred pa-
tients with a mean articular defect of 5.2 cm2 were fol-
lowed 2 to 9 years (mean, 4). Clinical assessment param-
eters included a modification of the Cincinnati scale and
the Lysholm and Tegner scoring systems. Isolated femoral
condyle defects fared best, with 96% good or excellent
results, followed by 89% good or excellent results in pa-
tients with osteochondritis dissecans, and 76% good or
excellent results in patients who had associated ACL tear
and reconstruction. Clinically, there is statistical improve-
ment in all categories. There is no evidence of deteriora-
tion over time. The results of patellar defects, although
initially inferior, gradually improved as autologous chon-
drocyte implantation was combined with wide excision of
the lesions and alignment procedures. Thirty patients had
a second-look arthroscopy and histologic examination. Bi-
opsy results revealed that the presence of hyaline-like
repair correlated with favorable outcome. In addition, 19
Figure 5. Autologous chondrocyte implantation procedure.
This schematic demonstrates the steps of this procedure
including articular cartilage biopsy procurement, growing of
the chondrocyte cells over a 21-day period, graft site prepa-
ration, procurement of the periosteal graft from the proximal
and medial tibias, and implantation of chondrocytes under
the “water-tight” periosteal flap that is then sealed with fibrin
glue.
Vol. 26, No. 6, 1998
of 25 biopsies showed some blend of hyaline repair. Bio-
mechanically, the use of an arthroscopic probe, developed
by Lyyra et al. of Finland,29 demonstrated that the stiff-
ness of normal articular cartilage (3.08 N) is comparable
with hyaline repair (2.77 N) but different from fibrous
repair (1.23 N).
The international autologous chondrocyte implantation
study,8 which is monitored by the Registry Advisory
Board, now has 12-month data on 249 patients and 24-
month data on 50 patients. As of December 8, 1997, 410
surgeons worldwide had performed 891 implantations
that are included in this Registry outcome study. This
study does not include the study series of Peterson (un-
published data, 1997). Of those patients with the baseline
data, the age range was 15 to 55 years (mean, 36); 67.2%
were men. Acute lesions were present in 67.6%, with a
mean size of 4.4 cm2. Most defects were in the medial
femoral condyle (60.8%) and lateral femoral condyle
(18.2%); the remaining lesions were trochlear (11.9%),
patellar (7.8%), and tibial (1.3%). There were 27.6% of
injuries related to sports; 76% of the patients had had at
least one previous procedure before the autologous chon-
drocyte implantation. Clinical assessment tools included
the modified Cincinnati rating scale (Fig. 6),36 a knee
physical examination, and adverse reaction data. This
comprehensive outcome system was used at 12- and 24-
month follow-up to demonstrate that overall patient and
clinician scores improved significantly from baseline (P ,
0.001). In addition, pain, swelling, and partial and full
giving way improved significantly (P , 0.001) when com-
paring baseline with 24-month follow-up data. On physi-
cal examination, joint line pain, effusion, and crepitus
improved by P , 0.001. Adverse event or complication
data are reported on all 891 patients treated with autolo-
gous chondrocyte implantation through December 8, 1997.
All adverse events reported to the Registry were re-
ported after autologous chondrocyte implantation (that is,
no adverse events were reported during the interval be-
tween cartilage harvest and autologous chondrocyte im-
plantation). The majority of the patients (779, or 87.4%)
reported no adverse events. Overall, 112 patients (12.6%)
have reported a total of 132 adverse events to the Registry
Figure 6. Modified Cincinnati knee documentation rating.
This system is optimal to subjectively interpret results of
articular cartilage repair techniques since its scale is a con-
tinuum of function from totally inactive to full and complete
return to sport (0 –10).
Articular Cartilage Lesions of the Knee 857
since its inception. Of these, 101 patients (11.3%) reported
an adverse event that was considered clinically relevant
by the Registry Advisory Board. The remaining 11 pa-
tients (1.2%) reported an adverse event that the Board
considered not clinically relevant. Of all patients reporting
an adverse event, 47 patients (5.3%) had adverse events
considered clinically relevant and possibly related to the
implantation procedure. Treatment failures were found in
18 patients (2%); reoperations were performed on 88 pa-
tients (9.9%). The most frequent procedures performed
included arthroscopic debridement, shaving, lavage, or
chondroplasty (58, or 6.5%), manipulation and lysis of
adhesions (21, or 2.4%), and patellar alignment (14, or
1.6%). The most frequently reported adverse events in-
cluded adhesions or arthrofibrosis (28, or 3.1%), hypertro-
phic changes to the defect site (21, or 2.4%), and detach-
ment and delaminations (16, or 1.8%).
There are several conclusions that may be elicited from
this 12- and 24-month comprehensive outcome study from
multiple global sites and surgeons. It appears that autol-
ogous chondrocyte implantation is most effective in the
treatment of femoral condyle lesions, less for the patella,
and least effective for the tibia. Patient and clinical out-
come data demonstrate significant improvements when
comparing the 24-month data with baseline. The autolo-
gous condrocyte implantation procedure is safe, as shown
by the low number of complications or adverse reactions.
As a consequence of this and other data, we have devel-
oped an algorithm and clinical pathway that may be used
in the treatment of articular cartilage defects.
CLINICAL MANAGEMENT
The most important issue in management of articular
cartilage defects is accurate and uniform characterization
of the historical details. The clinical survey history details
should include the patient’s age, the cause of the defect,
and previous surgical, medical, and family history. It is
imperative to use a clinical outcome tool to measure the
patient’s subjective symptoms. The problem with all car-
tilage repair studies to date has been the lack of standard
means of assessment. The modified Cincinnati rating
scale is an excellent tool for this because it allows both the
patient and the clinician to rate symptoms quantitatively
in relation to severity and functional level. The functional
level ranges from sedentary life to full return to sport (Fig.
6). A quality-of-life survey such as the Rand SF3643 helps
to optimally define the impact of the problem and inter-
ventions on the patient.
In addition to these survey techniques, the comprehen-
sive evaluation must include a knee physical examination,
standard radiologic assessment including weightbearing
projections, and an MRI that includes articular cartilage-
specialized sequences. Lastly, classification of the defect
description, including operative reports, videos, photo-
graphs, and diagrams, should be obtained. This compre-
hensive and systematic means of assessment must include
levels of specificity. As a consequence, the clinician must
define, characterize, and classify the local, regional, sys-
temic, medical, and family history factors that may influ-
858 Mandelbaum et al.
ence the progression, degeneration, or regeneration of the
defect.
Local and Regional Factors
To ensure uniform standards of evaluating methods of
articular cartilage repair it is imperative to develop clas-
sification methods that can be universally accepted. The
International Cartilage Repair Society20 has developed
a comprehensive method of documentation and classifi-
cation. The following variables are included in the
standards.
1. Etiology. Is the defect of acute or chronic onset? Was
there a specific acute mechanism or is the defect a conse-
quence of chronic repetitive injury? This is a difficult
element to determine because there may be a blend of
acute and chronic causes.
2. Defect Thickness. What is the thickness or depth of
the defect? The most accepted method of depth classifica-
tion is the Outerbridge40 classification (Fig. 7). This clas-
sification system characterizes changes into grades, with
grade 0 as normal, grade I as softening, grade II as fibril-
lation, grade III as fissuring, and grade IV as reaching the
depth of bone. Further specificity classifies grades I and II
as partial lesions, and grades III and IV as full-thickness
lesions. It is essential to know about penetration of the
Figure 7. The Outerbridge40 articular cartilage lesion clas-
sification system. This system has been considered the stan-
dard to date. A, grade I is a softening of articular cartilage; B,
grade II is fibrillation; C, grade III is fissuring; D, grade IV is
complete loss of the layers of articular cartilage with exposed
bone.
American Journal of Sports Medicine
tidemark, whether by an osteochondral lesion or from
previous drilling, and presence of subchondral cysts,
which can affect the “functional articular cartilage” unit.
Presence or absence of avascular necrosis, bone bruises, or
infarction is also important to know in the assessment of
these defects.
3. Size of the Lesion. Size, in square centimeters, must
be accurately measured, usually with a probe. Defects less
than 2 cm2 are considered small, those ranging from 2 to
10 cm2 are considered moderate, and defects greater than
10 cm2 are considered large.
4. Degree of Containment. Is the defect contained or
uncontained? Is it well circumscribed such that the lesion
is shouldered (as one can observe on the sagittal MRI) or
not (Fig. 8)? When a lesion is poorly contained or shoul-
dered, whether by size or quality of margin, there is a
consequent loss of joint space on radiographs.
5. Location. Where is the defect located? Is it mono-, bi-,
or multipolar? Each of these examples may have different
reparative and degenerative variables as well as
prognoses.
6. Ligament Integrity. Are the cruciate ligaments intact,
or are there partial or complete tears? If there are tears, is
there instability, or has the knee been reconstructed so
that it is now stable?
7. Meniscus Integrity. Are the menisci intact? If not,
was a partial, a subtotal, or a complete meniscectomy,
or meniscal repair or meniscal allograft replacement
performed?
8. Alignment. Is there normal, varus, or valgus align-
ment? If malalignment, how severe is it? Has an osteot-
omy been performed? If so, what type? It is essential to
know if there is patellofemoral malalignment and whether
or not corrective procedures have been performed.
Figure 8. Loading femoral defect schematic showing shoul-
dering and containment issues. Note that the smaller lesions
maintain the spatial height of the joint whereas the larger
lesions that are not well contained or shouldered tend to lose
height and can result in mechanical symptoms and
degeneration.
Vol. 26, No. 6, 1998
9. Previous Management. Has there been previous sur-
gery or treatment? If this is not the first procedure, what
type of treatment option or surgery was previously per-
formed? Was it a debridement, drilling, pick procedure,
bone graft, allograft, or mosaicplasty?
10. Radiologic Assessment. Standard projections includ-
ing weightbearing AP views must be included. Presence of
mild, moderate, or severe narrowing, osteophytes, and
cysts must be recorded.
11. Assessment by MRI. Using articular cartilage three-
dimensional and fat-suppression MRI techniques will al-
low visualization of the chondral and subchondral zones of
the functional articular cartilage unit. It is necessary to
determine the depth of a lesion, presence of bone bruises,
osteochondritis dissecans (stages I to IV), and any avas-
cular necrosis.
12. General Medical, Systemic, or Family History Issues.
1) Is there a rheumatologic history? Check for presence of
lupus, rheumatoid arthritis, or antigen HLA B27 associa-
tions. 2) Are there endocrine-related factors, including
thyroid problems, diabetes, or obesity? 3) Is there a family
history of osteoarthritis or collagen disorders such as
Ehlers-Danlos or Marfan’s syndrome?
THE CLINICAL ALGORITHM
The contemporary orthopaedic surgeon must understand
the complexities of articular cartilage biochemistry, bio-
mechanics, physiology, and the natural course of the le-
sion. This comprehensive interpretation then can be ap-
plied to the specific lesion and the particular dilemmas of
the problem. In addition, there are several important prin-
ciples that are essential.
1. With injury to the knee, there is a release of intra-
articular degradative enzymes such as stromelysin27 and
other cytokines7 that may contribute to degradation
rather than reparation.
2. Partial-thickness lesions do not heal; they remain
static as there are no biologic mechanisms to create a
reparative cascade.
3. Full-thickness lesions heal with fibrous type I fibro-
cartilage that lacks organization and composition to main-
tain wear characteristics and integrity for the long term.
4. Defects less than 2 cm2 that are well contained or
shouldered may be asymptomatic and nondegenerative for
a long, unspecified amount of time, thus potentially hav-
ing the most favorable prognosis.
5. Defects greater than 2 cm2 that are poorly contained
or shouldered have a lower probability of regenerative
success, which translates into pain, swelling, and lower
levels of function.33
6. Malalignments and ligament instabilities must be
identified and treated simultaneously or in sequence with
the articular procedure of choice.
7. Once a comprehensive history, physical examination,
and all survey and secondary diagnostics are completed,
the clinician has completed the necessary characterization
leading to a treatment plan. The criteria and parameters
for successful treatment must include the following
elements.
Articular Cartilage Lesions of the Knee 859
Effectiveness. 1) Histologically, hyaline cartilage rather
than fibrocartilage is preferred, as is creation of a resilient
surface that does not degenerate over time. 2) Is there
elimination of pain at rest, pain with motion, and pain
with increased dose of activity? Also, is there elimination
of swelling, stiffness, locking, and all mechanical symp-
toms? 3) There should be successful return of the athlete
to sport and activity.
Safety. There should be minimal adverse reactions or
complications, defined as an undesirable physical, psycho-
logical, or behavioral effect experienced by a patient or
subject associated and related with the use of the drug or
biologic intervention. These can occur on all levels. 1)
Local adverse events include hypertrophy, delaminations,
or fragmentation of graft or repair material, immunologic
reactivity, allergic reactions, oncologic processes, minimal
numbers of reoperations, bleeding, and septic arthritis. 2)
Regional adverse events include deep-vein thrombosis and
neurovascular injury. 3) Systemic adverse events include
infection and allergic reaction.
Once the efficacy and safety objective are understood, it
is appropriate to develop a practical algorithm that di-
vides protocols into femoral condyle groups of lesions less
than 2 cm2 and more than 2 cm2, and patellar and tibial
defects. The lesions that have the best potential prognosis
are the femoral defects less than 2 cm2.33 If the defect is
contained, it is appropriate to consider the primary mes-
enchymal stimulation options of drilling, debridement, or
the pick procedure. One may expect such treatment re-
sults to be successful in the short term, 3 to 5 years,
without progression to degenerative joint disease.14, 27
Hubbard17 stated that in the “low-demand” patient, who
is less physically active, the small focal and contained
defect has a 50% probability of success for up to 5 years. In
this group, clinical failure may be treated with autologous
chondrocyte implantation as a secondary option; this pro-
cedure has a 90% success rate for return to sports and
activities of daily living.34 Another option is mosaicplasty,
since it is a minimally invasive arthroscopic option3, 15 and
can be performed at low costs.
The probability of degenerative joint disease is higher in
knees with femoral lesions greater than 2 cm2 since the
repair fibrocartilage tissue will be unable to contain or
shoulder the defect. In the low athletic-demand patient,
the mesenchymal stimulation procedures are acceptable
as a primary approach; if this type of procedure fails,
autologous chondrocyte implantation remains the second-
ary option. In the higher athletic demand patient, autol-
ogous chondrocyte implantation may be considered the
primary approach because of its approximately 90% suc-
cess rate.34 Failure of autologous chondrocyte implanta-
tion may be revised by repeating the same procedure or by
using an osteochondral allograft. There is one allograft
failure that has been revised with autologous chondrocyte
implantation: tertiary failure of transplantation tech-
niques may be managed with an arthroplasty technique.
For lesions connected with femoral osteochondritis dis-
secans, initial approaches should include bioabsorbable
fixation of the fragment, if possible.10 If the fragment
cannot be repaired and is lost, primary techniques in
860 Mandelbaum et al.
lesions less than 2 cm2 include drilling, the microfracture
procedure, or mosaicplasty. If the lesion is greater than 2
cm2 or quite deep and cystic, autologous chondrocyte im-
plantation should be considered as a primary technique. If
the lesion is particularly deep, it may require staging with
an initial bone graft followed by autologous chondrocyte
implantation 4 to 12 months later.
For patellar defects, it is essential that the patellofemo-
ral malalignment be corrected concurrently. This advice
comes from experiencing initial fair or poor results when
autologous chondrocyte implantation alone was used in
this group, followed by significant improvements when
autologous chondrocyte implantation is combined with a
realignment procedure.34
Correcting lesions in the tibial condyle has been a chal-
lenge because this group of defects is small and the results
have been suboptimal with autologous chondrocyte im-
plantation. Therefore, autologous chondrocyte implanta-
tion or mosaicplasty are not recommended in patients
with this type of lesion. Unfortunately, mesenchymal
stimulation and debridement is the only option at this
time.
CONCLUSIONS AND FUTURE CHALLENGES
The challenge of repair and regeneration of the articular
surface of the knee continues to be significant despite
recent advances. Specifically, our objective is to have a
defect completely fill with hyaline cartilage that is resil-
ient and consistent. The analogy of the challenge of reach-
ing the moon is the model that embodies the sequential
evolutionary development. This challenge will require
well-disciplined studies that stress specificity and atten-
tion to strict biologic details. To date, we have gradually
expanded our capabilities by the approaches to these his-
torically insurmountable problems. Through comprehen-
sive survey and outcome tools, in conjunction with new
technologies such as autologous chondrocyte implantation
and arthroscopic tools for osteochondral grafting, our abil-
ity to manage these complex lesions have been greatly
increased. The issues of reestablishing the normal articu-
lar cartilage organization, morphology, and composition of
repair cartilage will enlist a prospective multidisciplinary
team including tissue engineers, orthopaedic clinicians,
and basic scientists to further this long-term project of
surface restoration. This project will require further ad-
vances in the areas of interpretive diagnostics such as
MRI,35 arthroscopic techniques, and tissue engineering.
Use of the arthroscopic biomechanical diagnostic probe is
essential to document the integrity of all repair tissues
regardless of option and method selected.
In the past, there has been a dearth of well-designed
clinical cohort outcome studies. From this point forth, a
uniform method of documentation and classification must
be adopted to allow honest and accurate comparisons over
time of all repair options.20 Further tissue engineering
innovations and the development of effective scaffolds
that may include collagen fiber gel, polylactic acid/poly-
glycolic acid, and decalcified matrix are required. These
scaffolds must meet the design criteria of adequate pore
American Journal of Sports Medicine
size to suppress fibrous ingrowth and potentiation of the
chondrogenic line, and they must allow contiguous adhe-
sion and proliferation of the chondrocytes. The role and
application of chondrogenic potentiating growth factors
such as basic fibroblast growth factor (bFGF), insulin
growth factor (IGF), and transforming growth factor
(TGF)-b) will need to be elucidated. Lastly, it is essential
to continue to develop an arthroscopic technique for place-
ment of a tissue-engineered and chondrocyte-impregnated
tissue fixated with bioabsorbable devices.
In conclusion, we are now in a rapid evolutionary se-
quence in the development of methods for restoration of
the violated articular cartilage surface.
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