The American Journal of Sports
The online version of this article can be found at:
2014 42: 886 originally published online February 4, 2014Am J Sports Med
Harold E. Hunt, Kamran Sadr, Allison J. DeYoung, Simon Gortz and William D. Bugbee
The Role of Immunologic Response in Fresh Osteochondral Allografting of the Knee
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American Orthopaedic Society for Sports Medicine
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The Role of Immunologic Response in Fresh
Osteochondral Allografting of the Knee
Harold E. Hunt,* MD, Kamran Sadr,yMD, Allison J. DeYoung,zMPA,
Simon Gortz,§MD, and William D. Bugbee,z§kMD
Investigation performed at Scripps Clinic, La Jolla, California, USA
Background: Osteochondral allografting, a restorative treatment option for articular cartilage lesions in the knee, involves trans-
plantation of fresh osteochondral tissue with no tissue matching. Although retrieval studies have not consistently shown evidence
of immunologic response, development of anti–human leukocyte antigen class I cytotoxic antibodies has been observed in allo-
Hypothesis: Postallograft antibody formation is related to graft size and may affect clinical outcome.
Study Design: Case-control study; Level of evidence, 3.
Methods: This study retrospectively compared 42 antibody-positive postallograft patients with 42 antibody-negative patients.
Groups were matched for age, sex, and body mass index but not intra-articular disease severity. Seventeen patients (20%)
were lost to follow-up. Of the remaining 67 patients (33 antibody-positive and 34 antibody-negative), average follow-up time
was 50.3 months (range, 24-165 months). Mean age was 38.1 years (range, 15-68 years) with 58% being male. Graft area
was categorized as small (\5 cm2), medium (5-10 cm2), or large (.10 cm2). Graft survival and Knee Society function scores
were used to measure clinical outcome.
Results: Of the 84 patients, 80 had graft area data. Of 27 patients with large graft area, 19 (70%) had positive postoperative anti-
body screens, compared with 1 of 16 (6%) with small graft area (P \ .001). Graft survival rates in the antibody-positive and
antibody-negative groups were 64% and 79%, respectively (P = .152). Mean postoperative Knee Society function scores in sur-
viving antibody-positive and antibody-negative groups were 88.3 and 84.6 points, respectively (P = .482).
Conclusion: Antibody development after fresh, non-tissue-matched osteochondral allograft transplants in the knee appears
related to graft size. No difference was observed in clinical outcome between groups. Graft survival is multifactorial, and the effect
that the immunologic response has on clinical outcome merits further investigation.
Keywords: cartilage repair; osteochondral allograft; immunology; immune response
Large articular cartilage injuries of the knee have limited
treatment options and are a major concern. Without surgi-
cal intervention, osteochondral injuries can lead to pro-
development of arthrosis.20,26Osteochondral lesions in
the aging population can be successfully addressed with
some form of arthroplasty. However, in our younger
patients, treatment modalities are more limited with vary-
ing rates of success.
Many surgical techniques have been developed to
address cartilage injuries, including chondroplasty, micro-
fracture, osteochondral autologous transfer, autologous
chondrocyte implantation, and osteochondral allograft
transplantation. These techniques have demonstrated lev-
els of success within their pathologic indications. At our
institution, current osteochondral allografting techniques
utilize fresh, cold-stored osteochondral allograft tissue
that is transplanted into the articular cartilage or osteoar-
ticular defect. Graft size varies with defect size but usually
ranges from 3 to 30 cm2, which provides an option for
reconstructing and restoring the surface of the articular
surface of the knee joint with biologically appropriate,
mature, viable hyaline cartilage.11As opposed to frozen
or freeze-dried allograft tissue, fresh osteochondral tissue
is utilized because it contains larger numbers of viable
chondrocytes. This technique is used to treat a broad spec-
trum of articular cartilage lesions,2,3,19ranging from focal
kAddress correspondence to William D. Bugbee, MD, Division of
Orthopaedic Surgery, Scripps Clinic, 10666 North Torrey Pines Road,
*Advanced Orthopaedics and Sports Medicine Specialists, Denver,
yDepartment of Orthopaedic Medicine, Kaiser Permanente, Fremont,
zDivision of Orthopaedic Surgery, Scripps Clinic, La Jolla, California,
§Department of Orthopaedic Surgery, University of California–San
Diego, San Diego, California, USA.
One or more of the authors has declared the following potential con-
flict of interest or source of funding: W.D.B. is a consultant to the Joint
Restoration Foundation, a nonprofit tissue bank.
The American Journal of Sports Medicine, Vol. 42, No. 4
? 2014 The Author(s)
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chondral defects10to established localized osteoarthrosis.13
Overall, osteochondral allograft transplantation has dem-
onstrated success rates between 50% and 90% for the treat-
ment of focal chondral and osteochondral defects and
osteochondritis dissecans, as well as posttraumatic, osteo-
necrotic, and bipolar lesions in the knee.1,3,4,12,13While
graft failure is often identified by radiographic evidence
of bony nonunion, late fragmentation, graft collapse or
fracture, and/or cartilage deterioration,22
investigate cellular and/or structural causes for such fail-
ures. Research to date has revealed several important fac-
tors in graft survival, including cartilage cell viability after
storage and effective osseous support.10,13,31Despite no
clear demonstration in prior studies, the host’s immuno-
logic response might also play a key role in the success of
Unlike other forms of allogenic transplantation, fresh
osteochondral allografts are not HLA (human leukocyte anti-
gen) or ABO blood group matched before implanting. In addi-
tion, postallograft patients received no immunosuppressive
response. Despite current practices, the success rate of osteo-
chondral allografts has been high enough to support its con-
ramifications of this procedure remain an important consid-
eration and might allow its use to further improve this treat-
ment and prevent graft failures secondary to host rejection.
Historically, osteochondral allograft immunology has
been studied for use in tumor reconstruction. It is well
understood that allograft immunogenicity is reduced by
freezing or freeze-drying techniques6,9; however, these
methods of preserving allografts are known to cause a sig-
nificant decrease in viable chondrocytes available to sus-
tain the hyaline cartilage allograft tissue.23Studies have
clearly revealed that isolated articular chondrocytes and
matrix components (eg, proteoglycans) are immunogenic
but the intact hyaline cartilage matrix is relatively immu-
noprivileged.7,15Observations suggest that the intact artic-
ular matrix protects the chondrocytes because of its
structure (‘‘pore size’’), therefore making it difficult for
cell-surface antigens to be recognized by the body’s
The role of the host immune system with potential graft
rejection has not been clearly determined. Two retrieval
studies of human failed fresh osteochondral allografts
showed little or no histologic evidence of immune-mediated
response and no evidence of frank transplant rejection.14,22
Conversely, studies by Stevenson28in canines and Sirlin
et al27in humans have shown sensitization to fresh osteo-
chondral allograft transplants with the development of
anti-HLA class I antibodies in a significant number of allo-
graft recipients. These studies demonstrate activating the
recipient’s humoral immune system and validating the
potential interplay between the host body’s immune sys-
tem and fresh osteochondral graft rejection.
We hypothesized that postallograft antibody formation
is related to graft size. Thus, the objectives of this study
were to determine (1) the relationship between total graft
area and development of antibodies and (2) the effect of
postallograft antibody formation on clinical outcomes.
MATERIALS AND METHODS
Using our institutional review board–approved fresh osteo-
chondral allograft outcomes database, we retrospectively
reviewed and identified 426 fresh osteochondral allografts
of the knee (376 patients) performed from 1983 through
2006. We identified 42 allograft recipients (42 knees) that
met our inclusion criteria. To be included, a patient had
to have (1) a negative preoperative anti-HLA class I cyto-
toxic antibody screen that converted to a positive antibody
response postoperatively and (2) a minimum follow-up of 2
years. Patients were excluded if they had a positive preop-
erative antibody screen or if any laboratory data were
missing. This patient cohort was then matched to a similar
group of 42 patients (42 knees) who were negative pre- and
postoperatively for anti-HLA class I cytotoxic antibodies.
The groups were matched 1:1 for age, sex, and body mass
index but not for intra-articular disease severity.
Of the 84 patients initially included in the study, 17
(20%) were lost to follow-up. Of the remaining 67 patients,
33 were in the antibody-positive group and 34 were in the
antibody-negative group. Table 1 describes patient demo-
graphics (including height, weight, body mass index, and
total graft area), graft location (distal femur, proximal
tibia, trochlea, patella, or multifocal), and graft type
(plug or shell) of the 67 remaining patients with available
follow-up data. The groups consisted of 39 male and 28
female patients, with a mean age of 38.1 years (range,
All procedures involved osteochondral allograft transplan-
tations in the knee, utilizing fresh unmatched tissue.
Grafts were processed in accordance with standards of
the American Association of Tissue Bank either (1) at the
regional tissue bank of the University of California–San
Diego and stored at 4?C in lactated Ringer solution con-
taining 1 g/L of cefazolin and 10 g/mL of gentamicin for 2
to 6 days (n = 10) or (2) at a commercial tissue bank and
stored at 4?C in proprietary tissue culture medium for 2
to 25 days (n = 74). Grafts were sized based on an antero-
posterior radiograph of the recipient and a direct measure-
ment of the donor. Two experienced surgeons from 2
institutions (W.D.B. at Scripps Clinic and Dr F. Richard
Convery at University of California–San Diego) performed
the procedures using similar techniques, utilizing the
press-fit plug (dowel) technique (n = 47), the shell grafting
technique (n = 30), or a combination of the 2, when multi-
ple lesions were present (n = 7).11
Both the press-fit plug and the shell grafting techniques
involve a limited arthrotomy of the knee, similar to that
used for autologous osteochondral transfer systems. With
the press-fit plug technique, an area including the articu-
lar lesion is cored out and replaced with a same-sized
osteochondral core taken from the identical region of the
articular surface from a size-matched knee allograft. The
plug grafts usually range from 15 to 35 mm in diameter
and 3 to 10 mm in depth; for this study, plug grafts were
7.1 6 3.5 cm2. Larger lesions are treated with overlapping
Vol. 42, No. 4, 2014Immunologic Response in Knee Allografts 887
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allograft plugs. Fixation is not usually necessary with the
press-fit technique but can be supplemented with small
bioabsorbable chondral darts if unstable. With the shell
grafting technique, a hand-shaped osteochondral allograft
piece is prepared to precisely replace the damaged osteoar-
ticular area with regard to size, shape, contour, and depth
and is fixed with chondral darts or 3.0-mm cannulated
screws. This shell technique is typically used for larger
lesions; for this study, shell grafts were 14.5 6 10.4 cm2.
Care is taken to match the articular contour as precisely
as possible. In addition, copious irrigation with pulsatile
lavage is utilized to remove the cellular components pres-
ent in the subchondral bone of the graft. A standard lay-
ered closure with a small postoperative drain is utilized.
Postoperatively, patients are allowed early range of motion
with toe touch–only weightbearing for 8 to 12 weeks. No
immunosuppressive or immunomodulatory medications
No HLA or blood-group matching was performed. The
presence of HLA class I antibodies (anti-HLA cytotoxic anti-
bodies) was measured preoperatively and 3 months postop-
eratively via serum samples, based on a standard (National
Institutes ofHealth) long-incubation
dependent assay (with and without dithiothreitol to identify
immunoglobin G vs M antibodies).27All patients in both
groups had no detectable anti-HLA class I cytotoxic anti-
body in preoperative samples.
Intraoperative data were collected on each patient,
including total graft area (cm2) and graft location. Each
patient’s total graft area was categorized as small
(\5 cm2), medium (5-10 cm2), or large (.10 cm2). Patients
returned for regular follow-up visits at 3 months, 6
months, 1 year, and every year thereafter. Clinical evalua-
tion included the Knee Society function score. While all
patients were invited for follow-up in clinic, some were con-
tacted by telephone. All reoperations were documented.
Comparison of Antibody-Positive and Antibody-Negative Patientsa
Antibody-Positive GroupAntibody-Negative Group
Recipient FactorsNo. Mean 6 SD or %No.Mean 6 SD or %
Age at surgery, y
Body mass index
Plug 1 shell grafts
Multifocal (2 sites)
Plug 1 shell grafts
Multifocal (31 sites)
3337.9 6 12.2 3438.3 6 9.8.904
68.1 6 4.2
172.8 6 33.4
26.1 6 4.4
13.2 6 9.7
6.9 6 1.7
16.4 6 12.0
14.6 6 1.5
69.6 6 3.7
185.9 6 44.3
26.9 6 5.4
7.4 6 3.8
7.0 6 4.0
9.1 6 0.9
2.6 6 1.8
56.2 6 38.7
2.3 6 1.4
49.1 6 27.5
aBMI, body mass index; SD, standard deviation.
bGraft area was summed for multifocal lesions.
cMean number of previous surgeries out of those patients in each group who had any previous surgery.
888Hunt et alThe American Journal of Sports Medicine
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Any revision allografting or conversions to arthroplasty
were considered failures.
Data were analyzed with SPSS v. 13.0 (SPSS Inc, Chicago,
Illinois, USA). Independent t tests were used for continu-
ous variables; chi-square tests were used for categorical
variables. The Mann-Whitney U test was used to compare
means of continuous variables not normally distributed.
An odds ratio was calculated to measure the risk of devel-
oping HLA class I cytotoxic antibodies by category of graft
size. All statistical tests were 2-tailed, and the alpha level
was set at 5%.
In the study group, 80 of the 84 patients had intraoperative
graft area data. Of all osteochondral allograft procedures,
27 grafts were classified as large (34% of total; 7 plug, 13
shell, and 7 plug 1 shell), 37 as medium (46% of total; 24
plug and 13 shell), and 16 as small (20% of total; 16
plug). Positive postoperative anti-HLA antibody screens
were found in 19 of 27 patients (70%) with the large graft,
20 of 37 patients (54%) with the medium, and 1 of 16
patients (6%) with the small. There was a significant dif-
ference between the large and small graft groups (P \
.001) with regard to the development of anti-HLA antibod-
ies. No statistical difference was found between large and
medium groups and between medium and small groups.
With regard to location of the lesions, 17 of the 45 fem-
oral condyle lesions (38% of total; 11 plug and 6 shell
grafts; 1 small, 15 medium, 1 large), 6 of 6 of the tibial pla-
teau lesions (100% of total; all shell grafts; 4 large, 2
unknown size), and 2 of 10 of the patellofemoral lesions
(20% of total; 1 plug and 1 shell graft; 2 medium) developed
positive anti-HLA antibodies. In patients that had 2 or
more graft locations, 17 of 23 (74% of total; 3 plug, 8 shell,
and 6 plug 1 shell grafts; 3 medium, 14 large) went on to
develop anti-HLA antibodies.
Mean follow-up was 52.7 months (range, 24-165
months). Graft survival (not requiring conversion to
arthroplasty or revision allograft) in the positive anti-
HLA antibody group and negative anti-HLA antibody
group was 64% (21 of 33) and 79% (27 of 34), respectively
(P = .152). In the antibody-positive group, 39% (13 of 33)
of patients required reoperation due to the allograft,
whereas in the antibody-negative group, 21% (7 of 34) of
patients required reoperation (P . 0.2) (Table 2). In the
antibody-positive group, 3 plug grafts (area, 7.4 6
1.7 cm2; 3 medium), 8 shell grafts (area, 20.3 6 16.1 cm2;
2 medium and 6 large), and 1 plug 1 shell graft (area,
13.3 cm2; 1 large) failed. Similarly, in the antibody-
negative group, 5 plug grafts (area, 7.8 6 3.8 cm2; 2 small
and 1 medium) and 2 shell grafts (unknown area) failed.
There were no significant differences in failure type, time
to failure, graft type, graft area, or graft location between
antibody-positive and antibody-negative groups. At last
follow-up, the mean postoperative Knee Society function
scores for the surviving anti-HLA antibody-positive and
antibody-negative groups were 88.3 points and 84.6 points,
respectively (P = .482).
The use of fresh osteochondral allografts in biological
reconstruction of the knee has an extensive clinical history
dating back to the pioneering work of Erich Lexer in
1908.17In several North American institutions since the
1970s, transplantation of small-fragment, fresh osteochon-
dral allografts has evolved into a more routine procedure
used to treat osteochondral lesions and periarticular
trauma.5,21,25Continued clinical interest has led to advan-
ces and refinements in fresh osteochondral allografting
that allowed achievement of good or excellent results in
as many as 90% of patients with follow-up of 1 to 12 years
and survivorship of up to 85% at 10 years.1,3,10,13,21
Although alternative procedures such as microfracture,
osteochondral autologous transfer, and autologous chon-
drocyte transplantation show promise for localized chon-
procedures have generally not been successful in the treat-
ment of patients with multiple or very large osteochondral
defects or with more complex, advanced joint disease.
Thus, osteochondral allografting remains an attractive
alternative in this patient population.
Historically, bone and chondral allografts have not been
tissue- or blood-type matched, something routinely per-
formed in protocols involving vascularized organ transplan-
tation. Processed osteoarticular musculoskeletal allografts
used in tumor reconstruction were either frozen or freeze-
dried, which results in a smaller or nonexistent immuno-
logic response.7,29Unlike these historical predecessors, we
used fresh osteochondral allografts that did not involve
a freezing process and that had a higher potential
Reoperation Procedures Performed on Antibody-Positive
and Antibody-Negative Patientsa
No. of Antibody-
No. of Antibody-
Plug 1 shell grafts
Conversion to arthroplasty
Plug 1 shell grafts
Total, No. (%)
18 of 33 (55)10 of 34 (29)
aOCA, osteochondral allograft transplantation.
bIncluding 1 osteochondral autograft transfer system procedure.
cDebridement, loose body removal, hardware removal.
Vol. 42, No. 4, 2014Immunologic Response in Knee Allografts889
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immunogenicity. Similarly, fresh osteochondral allografts
have not been matched for HLA or blood group antigens.3,4
In our study, we sought to examine the relationship
between osteochondral graft size and anti-HLA antibody
formation. We also wanted to determine if the presence
of anti-HLA antibodies would confer differences in the
Knee Society score or the graft survival rate. We were
able to demonstrate a clear increase in antibody formation
with increase of graft diameter. Knee Society scores
groups were equivalent. We were able to illustrate a non-
significant trend of graft survival, with the antibody-
positive group having a survival rate of 64% and the
antibody-negative group, 79%.
In both animal and human studies, fresh osteochondral
allografts have been shown to produce a variable immuno-
logic response; however, the mechanism is poorly under-
stood. It is important to recognize that osteochondral
allografts are a composite of 2 tissue types, bone and artic-
ular cartilage, which may independently elicit a host
response to either the cells or the antigen-presenting pro-
teins. Langer and Gross showed that isolated chondrocytes
and shavings of articular cartilage were immunogenic in
animals; however, sensitization of the host did not occur
if the cartilage matrix remained intact.15Similarly, Kandel
et al14histologically evaluated 44 failed human allografts
and found no histologic evidence of transplant rejection.
These studies, along with others, support the theory that
articular cartilage, when intact, is immunologically privi-
leged and does not sensitize the host.4,15Conversely, allo-
graft bone has been shown to be antigenic, as the
marrow and soluble proteins stimulate an immune
response16,30; thus, it is likely that the bony part of
the allograft creates the observed immune response. While
studies have shown that reducing surface antigens (by
freezing) or matching HLA antibodies has led to improved
osseous integration and clinical outcomes,7,27in this study
the immunogenic load was related to the size (small vs
large) and type (plug vs shell) of the implanted graft,
with larger, shell grafts (area, 14.3 6 5.2 cm2) more likely
to elicit an antibody-positive response than smaller, plug
grafts (area, 6.5 6 3.2 cm2; P \ .001).
humans have shown that a fresh osteochondral allograft
can evoke an immune response. Stevenson28studied fresh
and frozen osteochondral allografts in canines—leukocyte
antigenmatched and mismatched—and discovered a signif-
icantly larger immune response to fresh mismatched osteo-
chondral allografts. Sirlin et al27showed that humans who
received fresh osteochondral allografts generated serum
anti-HLA class I antibodies. Although the presence of
anti-HLA antibodies postallograft did not correlate with
frank graft failure, it did correlate with inferior appear-
ance of the graft-host interface on magnetic resonance
imaging studies. Friedlaender7also detected an immuno-
logic response directed against osteochondral allograft in
humans. This humoral response suggested that cartilage
were capable of sensitizing osteochondral allograft recipi-
ents. Phipatanakul et al24measured the immunologic
in bothcanines and
response to cartilage-specific protein in 14 patients with
large shell osteochondral allografts. They demonstrated
the presence of antibodies to cartilage-specific protein in
the sera of 8 of 14 cartilage allograft recipients; however,
no difference in clinical outcomes was observed due to
the presence of these antibodies. Despite these findings,
the clinical significance of the immunologic response has
yet to be fully demonstrated; other factors—including the
effects on future pregnancy or organ or tissue transplanta-
tion, in addition to clinical outcomes—may also be relevant
to overall patient satisfaction. Although in this study we
evaluated the incidence of antibody formation and the effect
on graft performance and clinical outcome, it should be
noted that little is also known about the potential systemic
effects of development of anti-HLA antibodies. Studies
designed to investigate the relationship between graft size
and levels of circulating antibodies, in addition to the modes
of failure experienced (ie, bony nonunion, late fragmenta-
tion, graft collapse or fracture, and/or cartilage deteriora-
tion), would be useful to tease out some of the subtle
details associated with the immunogenic response due to
the implanted allografts.
The results of this study show that the development of
anti-HLA cytotoxic antibodies after fresh, nonmatched
osteochondral allograft transplantation
appears to be related to graft size. A large osteochondral
graft (.10 cm2) is 36 times more likely to elicit an antibody
response than a small graft (\5 cm2) (P\.05). Despite this
difference in antibody generation, the graft survival out-
come between the 2 groups was similar. This finding
brings into question the clinical effect of a positive anti-
body response. The fact that we could not demonstrate
a difference in graft survival rate (P = .152; 64% vs 79%)
or Knee Society function scores (P = .482; 88.3 vs 84.6
points) in the positive and negative groups may be due to
either small cohort size or other unaccounted patient vari-
ables, such as extent of disease or activity level. Overall,
the presence of antibodies may play only a part in the mul-
tifactorial success of osteochondral allograft transplanta-
tion. A study with a larger cohort of patients matched for
other variables, including disease and lesion size, may pro-
vide evidence of clinical consequence of antibody positivity.
Several limitations were present in this study. Although
antibody-positive and antibody-negative patient cohorts
were matched for age, sex, and body mass index, they
were not matched for intra-articular disease severity.
One could surmise that the larger the allograft, the greater
the intra-articular disease of the patient. With allografts in
the antibody-positive group (19 large, 20 medium, and 1
small) and a reverse distribution in the antibody-negative
group (8 large, 17 medium and 15 small), the intra-
articular disease severity may have been greater in the
antibody-positive group. Furthermore, we included 2 tech-
nique types within our subgroups: press-fit plug (dowel)
technique (56% of implanted grafts), the shell grafting
technique (36%), and a combination of the 2 (8%). Even
though these 2 techniques can be used to address similar
lesions and graft sizes, they can also address lesions in dif-
ferent locations of the knee and have different amounts of
graft exposure secondary to the technique. The antibody-
890 Hunt et alThe American Journal of Sports Medicine
by guest on November 11, 2015ajs.sagepub.comDownloaded from
positive group included more shell grafts (17 shell vs 10 Download full-text
plug) in its cohort than the antibody-negative group (7
shell vs 26 plug) and also had a higher incidence rate in
shell grafts versus plug grafts (71% vs 28%, respectively).
Twenty percent of patients, greater than 2 years from
index surgery, were lost to follow-up.
The HLA matching of all allograft patients with the allo-
graft donor is logistically difficult and expensive. If future
studies confirm the effect of HLA antigens on the clinical out-
come of osteochondral allografting, HLA typing may be a nec-
essary part of the procedure’s protocol. The obstacles incurred
while putting this into practice would be considerable. Not
only the expense of the immunologic testing but also the
vast size of the donor pool required to support histocompati-
bility and graft size requirements would have to be consid-
ered. Currently, a shortage of allograft tissue available for
transplanting exists and the inclusion of HLA typing would
adversely affect this already limited resource. Until definitive
evidence is available, matching will likely remain optional.
In association with other studies, this study confirms
that HLA sensitization of the host does occur with many
osteochondral allografts of the knee. Due to the small size
of our cohorts and the multifactorial nature of graft failure,
drawing a correlation between host immunologic sensitiza-
tion and ultimate graft failure is difficult. While there was
a clear effect of graft size (and, as a result, graft type) on
positive antibody formation, other factors (eg, graft location
and disease state) may influence clinical outcomes as com-
monly experienced in the allograft treatment algorithm.11
Clinical results with fresh, nonmatched osteochondral allo-
grafts have been sufficiently successful in appropriately cho-
sen patients to justify their continued use. The results of
this study are provocative and underline the need for larger,
more controlled studies, specifically analyzing the effects of
graft location and disease state, to aid in understanding the
immunologic consequences of osteochondral allograft trans-
plantation on clinical outcomes.
The authors thank Julie McCauley, MPHc, for her help in
preparation of this manuscript.
1. Aubin PP, Cheah HK, Davis AM, et al. Long-term followup of fresh
femoral osteochondral allografts for posttraumatic knee defects.
Clin Orthop Relat Res. 2001;391:S318-S327.
2. Bugbee WD.Freshosteochondral
3. Chu CR, Convery FR, Akeson WH, et al. Articular cartilage transplanta-
tion: clinical results in the knee. Clin Orthop Relat Res. 1999;360:159-168.
4. Convery FR, Meyers MH, Akeson WH. Fresh osteochondral allograft-
ing of the femoral condyle. Clin Orthop Relat Res. 1991;273:139-145.
5. Czitrom AA, Langer F, McKee N, et al. Bone and cartilage allotrans-
plantation: a review of 14 years of research and clinical studies. Clin
Orthop Relat Res. 1986;208:141-145.
6. Elves MW. Newer knowledge of the immunology of bone and carti-
lage. Clin Orthop Relat Res. 1976;120:232-259.
7. Friedlaender GE. Immune responses to osteochondral allografts: cur-
rent knowledge and future directions. Clin Orthop Relat Res.
8. Friedlaender GE, Horowitz MC. Immune responses to osteochondral
allografts: nature and significance. Orthopedics. 1992;15:1171-1175.
9. Friedlaender GE, Strong DM, Sell KW. Studies on the antigenicity of
bone: I. Freeze-dried and deep-frozen bone allografts in rabbits.
J Bone Joint Surg Am. 1976;58:854-858.
10. Ghazavi MT, Pritzker KP, Davis AM, et al. Fresh osteochondral allo-
grafts for post-traumatic osteochondral defects of the knee. J Bone
Joint Surg Br. 1997;79:1008-1013.
11. Gortz S, Bugbee WD. Allografts in articular cartilage repair. J Bone
Joint Surg Am. 2006;88:1374-1384.
12. Gross AE, McKee NH, Pritzker KP, et al. Reconstruction of skeletal
deficits at the knee: a comprehensive osteochondral transplant pro-
gram. Clin Orthop Relat Res. 1983;174:96-106.
13. Gross AE, Shasha N, Aubin P. Long-term followup of the use of fresh
osteochondral allografts for posttraumatic knee defects. Clin Orthop
Relat Res. 2005;435:79-87.
14. Kandel RA, Gross AE, Ganel A, et al. Histopathology of failed osteo-
articular shell allografts. Clin Orthop Relat Res. 1985;197:103-110.
15. Langer F, Gross AE. Immunogenicity of allograft articular cartilage.
J Bone Joint Surg Am. 1974;56:297-304.
16. Lewandrowski KU, Rebmann V, Passler M, et al. Immune response
to perforated and partially demineralized bone allografts. J Orthop
17. Lexer E. Substitution of whole or half joints from freshly amputated
extremities by free plastic operations. Surg Gynecol Obstet.
18. Maroudas A, Bullough P, Swanson SA, et al. The permeability of
articular cartilage. J Bone Joint Surg Br. 1968;50:166-177.
19. McDermott AG, Langer F, Pritzker KP, et al. Fresh small-fragment
osteochondral allografts: long-term follow-up study on first 100
cases. Clin Orthop Relat Res. 1985;197:96-102.
20. Messner K, Maletius W. The long-term prognosis for severe damage
to weight-bearing cartilage in the knee: a 14-year clinical and radio-
graphic follow-up in 28 young athletes. Acta Orthop Scand.
21. Meyers MH, Akeson W, Convery FR. Resurfacing of the knee with
fresh osteochondral allograft. J Bone Joint Surg Am. 1989;71:704-713.
22. Oakeshott RD, Farine I, Pritzker KP, et al. A clinical and histologic
analysis of failed fresh osteochondral allografts. Clin Orthop Relat
23. Pegg DE, Wang L, Vaughan D, et al. Cryopreservation of articular carti-
lage: part 2. Mechanisms of cryoinjury. Cryobiology. 2006;52:347-359.
24. Phipatanakul WP, VandeVord PJ, Teitge RA, et al. Immune response
in patients receiving fresh osteochondral allografts. Am J Orthop
(Belle Mead NJ). 2004;33:345-348.
25. Shasha N, Aubin PP, Cheah HK, et al. Long-term clinical experience
with fresh osteochondral allografts for articular knee defects in high
demand patients. Cell Tissue Bank. 2002;3:175-182.
26. Shelbourne KD, Jari S, Gray T. Outcome of untreated traumatic artic-
ular cartilage defects of the knee: a natural history study. J Bone
Joint Surg Am. 2003;85(suppl 2):8-16.
27. Sirlin CB, Brossmann J, Boutin RD, et al. Shell osteochondral allo-
grafts of the knee: comparison of MR imaging findings and immuno-
logic responses. Radiology. 2001;219:35-43.
28. Stevenson S. The immune response to osteochondral allografts in
dogs. J Bone Joint Surg Am. 1987;69:573-582.
29. Strong DM, Friedlaender GE, Tomford WW, et al. Immunologic
responses in human recipients of osseous and osteochondral allo-
grafts. Clin Orthop Relat Res. 1996;326:107-114.
30. VandeVord PJ, Nasser S, Wooley PH. Immunological responses to
bone soluble proteins in recipients of bone allografts. J Orthop
31. Zukor DJ, Oakeshott RD, Gross AE. Osteochondral allograft recon-
struction of the knee: part 2. Experience with successful and failed
fresh osteochondral allografts. Am J Knee Surg. 1989;2:182-191.
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