Baer 2007
Baer 2007
Baer 2007
A
nterior cruciate ligament (ACL) injuries are the most common complete
ligamentous injury to the knee [1]. They occur mainly in the young ath-
letic population, especially in young female athletes [2–4]. ACL injuries
have been reported to occur in an estimated 1 in 3000 people in the United
States population each year [5–8], with more than 100,000 ACL reconstruc-
tions performed annually [9–12]. Although bone-patellar tendon-bone (BPTB)
autograft has become the most common graft choice for ACL reconstruction
and is considered the reference standard [13–15], it also is associated with sig-
nificant morbidity including quadriceps weakness, patellofemoral pain, loss of
motion, patella fracture, patellar tendonitis, patella infera syndrome, early de-
generative joint changes, and arthrofibrosis [16–20]. Semitendinosus gracilis au-
tografts have become more popular for ACL reconstruction, with outcomes
similar to those of BPTB grafts without the extensor mechanism dysfunction;
however, deficits in knee flexor strength, variability in hamstring size, fixation
limitations, delayed incorporation, and surgeon experience have affected their
overall use [21–30]. As surgeons and patients look for ways to limit the signif-
icant morbidity associated with autograft harvest, allograft tissue has become
increasingly popular for ACL reconstruction. The senior author (C.D.H.)
has noted a significant increase in the use of allograft tissue among his col-
leagues for ACL reconstruction. Currently allograft tissue is used in approxi-
mately 30% of primary ACL reconstructions and in 90% of revision ACL
reconstructions in his practice.
Allograft tissue has the advantage of no donor-site morbidity, larger and pre-
dictable graft sizes, low incidence of arthrofibrosis, shorter operative time, and
0278-5919/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.csm.2007.06.010 sportsmed.theclinics.com
662 BAER & HARNER
outcomes can be obtained with both autograft and allograft BPTB reconstruc-
tions and that a bactericidal dose of 2.5 Mrad of irradiation as a means of graft
sterilization did not compromise the clinical outcome.
Poehling and colleagues [33] prospectively compared subjective and objec-
tive outcomes of patients undergoing ACL reconstruction with either BPTB
autograft (118 patients) or Achilles tendon allograft (41 patients) for up to 5
years of follow-up (average of 4.2 years for subjective measures and 2.2 years
for objective measures). Using the Rand 36-item health survey and the McGill
Pain Questionnaire, the authors found that patients undergoing allograft recon-
struction had significantly improved physical functioning for the first year fol-
lowing surgery, less severe pain for the first 3 months following surgery, and
fewer limitations in function throughout the follow-up period. Overall IKDC
values showed no differences between autograft and allograft ACL reconstruc-
tion except at the 2-year point, when 50% of autograft knees and 89% of allo-
graft knees were rated as normal or nearly normal (P ¼ .037). KT-1000
measurement values were less in autograft recipients (2.8 mm versus 3.0 mm
allograft; P ¼ .052), but side-to-side KT-1000 measurements revealed no differ-
ence between autograft and allograft, and the values were found to decrease
over the 5-year follow-up period. Additionally, in a related article, the authors
reported that analysis of surgical costs data found the mean hospital charge for
an ACL reconstruction was $4622 with allograft and $5694 with autograft [34].
The increased cost for autograft reconstruction resulted from increased operat-
ing room time and an increased likelihood of overnight hospitalization for pain
control with autograft recipients. Despite differences in graft type, fixation, and
treating surgeon, the authors concluded that similar long-term results in stabil-
ity and function were achieved with BPTB autograft and Achilles tendon allo-
graft reconstruction of the ACL, but that patients treated with allograft
reconstruction had less pain and functional limitations in the early postoperative
period.
Many practices have considered older patient age to be a relative indication
for using allograft tissue in ACL reconstruction. Barrett and colleagues [35] ex-
amined the clinical outcomes of patients 40 years or older having at least 2
years of follow-up after ACL reconstruction with BPTB autograft or allograft.
At final follow-up, subjective evaluation using a 15-question visual analogue
scale revealed no difference between patients treated with allograft or autograft.
IKDC functional levels were normal or nearly normal in 87% of patients in
the allograft group and in 96% of patients in the autograft group. KT-1000
side-to-side differences were 1.46 mm for the allograft group and 0.104 mm
for the autograft group. Final follow-up Tegner activity rating scale scores
and Lysholm scores did not differ between groups, but allograft-treated patients
had a quicker return to activities. There was one clinical failure in the allograft
group and none in the autograft group. The authors concluded that allograft
reconstruction allows a quicker return to sporting activities but has greater lax-
ity than autograft BPTB reconstruction. They believed that both graft choices
were highly effective and that the benefits and disadvantages of each graft
664
Table 1
Clinical outcome studies of autograft versus allograft anterior cruciate ligament reconstruction
Average age
Graft type # Patients (years) N/NN IKDC (%) Laxity (KT 1000)
Functional
Study Follow-up Differences/
Study Auto Allo Type Auto Allo Auto Allo (months) Auto Allo Auto Allo Conclusions
Rihn et al, BPTB BPTB RR 63 39 25.3 44 50.4 82.70 90.70 2.2 mm 1.3 mm No functional
2006 [32] differences
Low-dose
irradiation
does not affect
outcome
Poehling BPTB Achilles PC 118 41 25.4 29.7 50.4/26.4 50 89 2.8 mm 3.0 mm Improved
et al, 2005 (sub/obj) 2-year follow-up physical
[33] function first 2
years allograft
Less pain for first
665
666
Table 1
(continued)
Average age
Graft type # Patients (years) N/NN IKDC (%) Laxity (KT 1000)
Functional
Study Follow-up Differences/
Study Auto Allo Type Auto Allo Auto Allo (months) Auto Allo Auto Allo Conclusions
Peterson BPTB BPTB PC 30 30 25 28 64.6/62.5 88.6 90 67% 73% Autograft group
et al, 2001 (auto/allo) Average Lysholm <3 mm had slight
[14] scores side-to-side extension loss
(5-year Increased #
follow-up of allograft with
667
668 BAER & HARNER
examination, and four allograft and two autograft knees had an increased
pivot-shift examination. Fifty-three percent of autograft recipients and 7% of al-
lograft recipients had incisional-site complaints. The authors concluded that
BPTB autograft and allograft ACL reconstruction produced statistically similar
results at both 2 and 5 years and that allograft was an acceptable choice for pri-
mary ACL reconstruction.
Kleipool and colleagues [39] prospectively followed the results for a group of
62 patients who underwent ACL reconstruction with either fresh-frozen BPTB
allograft (36 patients) or autograft (26 patients). The patient populations were
similar in age, activity level, and associated injuries. Preoperatively the allograft
group had significantly worse Lachman and anterior drawer tests than the the
autograft group. At a mean follow-up of 52 months for the autograft group and
46 months for the allograft group, an IKDC rating of normal or nearly normal
had been achieved in 70% of the autograft group and 85% of the allograft
group. Lysholm scores averaged 95 in the autograft group and 94 in the allo-
graft group. No differences in Lachman, anterior drawer, pivot-shift, one-leg
hop test, or KT-1000 side-to-side difference was detected between groups.
Mild-to-moderate anterior knee pain was found in 42% of autograft recipients
and 53% of allograft recipients. Two autograft recipients had disabling anterior
knee pain; no allograft recipients had disabling pain. The investigators did find
that anteriorly placed tibial tunnels were associated with poorer outcomes and
increased laxity in both autograft and allograft groups. In a related study, Zijl
and colleagues [40] found no difference in tunnel enlargement following ACL
BPTB reconstruction with either autograft or allograft. Tunnel enlargement
did not correlate with clinical outcome, and enlargement of the tunnels was found
to decrease with time. These investigators again confirmed that malpositioned
tunnels led to poorer clinical outcomes, and they did see a trend of increased tun-
nel enlargement in anteriorly malpositioned tunnels. The authors concluded
from both studies that BPTB allograft was a good alternative to autograft tissue
with similar subjective and objective results at 4 years of follow-up and that tunnel
positioning is of great importance in preventing poor clinical outcomes.
Stringham and colleagues [15] retrospectively reviewed the results for 78 pa-
tients 34 months following ACL reconstruction with BPTB autograft (47 pa-
tients) or allograft (31 patients). The two groups of patients were similar in
age (25 years), activity level, time from injury to surgery, associated injuries,
and type of fixation used on both tibial and femoral sides. Both groups had
an equal satisfaction ratings postoperatively, and there was no difference be-
tween the two groups in subjective symptoms (pain, instability, swelling, and
locking). Objective results showed no difference for joint effusions, knee ten-
derness, range of motion, quadriceps atrophy, patellofemoral scores, or exten-
sion deficits. The authors found two trends in the study that did not reach
statistical significance. Eighty percent of autograft recipients versus 70% of al-
lograft recipients achieved good-to-excellent restoration of anteroposterior sta-
bility (< 3 mm side-to-side laxity difference), and patients who had undergone
allograft reconstruction had increased concentric peak extension torque results
670 BAER & HARNER
most patients and family members raise when the topic of using allograft tissue
is raised. Because of this concern, donor selection and screening has been em-
phasized as a crucial first step in assuring the safety of allograft tissue. The
American Association of Tissue Banks recommends serologic screening for hu-
man HIV, human T-cell leukemia virus, hepatitis B, hepatitis C, aerobic and
anaerobic bacteria, and syphilis as well as harvesting allograft tissue within
12 hours of cold ischemia time [44,45]. Many tissue banks perform polymerase
chain reaction testing for HIV to help lower the risk of HIV transmission.
When these steps are combined with freezing of the allograft tissue, the esti-
mated risk for HIV transmission with connective tissue allografts is estimated
to be 1:8,000,000 [46]. Individual tissue banks differ in their methods of pro-
curement, testing, and processing, and therefore the surgeon should be familiar
and comfortable with the methods used.
Bacterial infection following allograft ACL reconstruction is another major
concern for patients, families, and physicians. In 2002, the Centers for Disease
Control and Prevention (CDC) reported 26 cases allograft-associated bacterial
infections in an estimated 1 million allografts distributed for transplantation
[47]. Thirteen of the infections, including one death, were associated with Clos-
tridium spp. The source of the infection in eight of these cases was contaminated
frozen tendons used for ACL reconstruction. Of the remaining 13 cases, 11
were infected with gram-negative bacilli, 5 of which were polymicrobial, and
2 patients had negative cultures. Ten of these 13 cases involved frozen tissue
used for ACL reconstruction. The CDC identified 14 of the cases as associated
with a single tissue processor. The CDC made specific recommendations to tis-
sue banks to decrease the risk of bacterial contamination: culturing tissue be-
fore suspension in antimicrobial solutions, validating culture methods to
eliminate false-negative culture results, performing both destructive and swab
cultures, and limiting the time between death, refrigeration, and tissue retrieval.
The CDC went on to recommend using sterilization techniques including
gamma irradiation or sporicidal techniques when applicable to the graft source.
Barbour and colleagues [48] reported on four additional cases of Clostridium sep-
ticum infection following ACL reconstruction between 1998 and 2001. Again,
the transmission of disease was linked to tissue procurement and processing.
Two large studies examined postoperative infection following ACL reconstruc-
tion with either autograft or allograft tissue. In the first report, Williams and
colleagues [49] reviewed 2500 ACL reconstructions, 7 (0.3%) of which became
infected. In a more recent report, Indelli and colleagues [50] reviewed the infec-
tion rate following 3500 ACL reconstructions (60% allograft) performed at
Stanford University between 1992 and 1998. They found a deep infection
rate of 0.14%, with only two of six infections occurring in allograft-recon-
structed knees. No difference in infection rates existed between allograft and
autograft ACL reconstructions. These studies, as well as the reports from the
CDC, indicate that there is no increased risk for bacterial infection with allo-
graft tissue as long as the tissue bank undertakes preventive measures in pro-
curing and processing of graft tissue.
672 BAER & HARNER
Allograft tissue can be used for fresh grafts or preserved by three main
methods: cryopreserved, fresh-frozen, or freeze-dried. Fresh grafts are main-
tained in lactated Ringer’s solution at 4 C for up to 7 days. Fresh grafts main-
tain cell viability, but the short time frame available for accurate serologic
testing limits their use in clinical practice. Cryopreservation uses a controlled
rate of freezing with a cryoprotectant media to maintain cell viability. Studies
have found that 10% to 40% of cells in cryopreserved soft tissue grafts maintain
viability [51]. The importance of donor-cell viability is questioned in ACL re-
construction, however. Several studies have demonstrated the rapid repopula-
tion of allograft tissue with host cells within 4 weeks of transplantation [52,53],
and results using cryopreserved tissues have not been superior to those for
fresh-frozen allograft tissue [42]. Fresh-frozen tissues are stored at 80 C, are
simple and less expensive to prepare than cryopreserved or freeze-dried grafts,
and lack donor-cell viability. The success of ACL reconstruction with fresh-
frozen grafts, as well as their ease of preparation and storage, has made
fresh-frozen tissue the most common grafts used for soft tissue reconstruction
[42,48]. Freeze-dried allograft tissue also is commonly used. Freeze-drying in-
volves dehydration of graft tissue during freezing in a vacuum. Freeze-drying
alters the color, appearance, and strength of the graft but allows extended stor-
age at room temperature [42,48]. Results of ACL reconstruction with freeze-
dried grafts have been mixed. Indelicato and colleagues [54] found that patients
receiving fresh-frozen grafts faired slightly better than patients receiving freeze-
dried grafts. Several other studies have found successful clinical outcomes fol-
lowing ACL reconstruction with freeze-dried tissue (see the article by Mahiro-
gullari and colleagues in this issue) [55,56].
Secondary sterilization methods such as ethylene oxide or gamma irradiation
may be used to decrease the risk of bacterial or viral transmission. Ethylene
oxide treatment has been used with a wide variety of biologic tissues, but sev-
eral studies have shown problems in tendon allografts with graft dissolution,
synovial effusions, and poor clinical outcomes [57,58]. Therefore its use is
not recommended for ligament reconstruction. Gamma irradiation also has
been used for secondary sterilization. Gamma irradiation neutralizes both vi-
ruses and bacteria by direct destruction of the organism’s genome and through
free-radical production. Many tissue banks irradiate tissues with 1.5- to 2.5-
Mrad doses. These doses are effective at destroying many micro-organisms,
but recent studies have shown that doses as high as 4 Mrad are required to neu-
tralize HIV from BPTB allografts [59]. Schwartz and colleagues [60] demon-
strated in a goat model that a 4-Mrad dose of gamma irradiation had
a significant negative effect on allograft tissue load relaxation, stiffness, and
maximum force compared with controls at zero and 6 months postoperatively.
Other studies have shown that doses of gamma irradiation as low as 2 Mrad
have deleterious effects on the initial strength and stiffness of soft tissue allo-
grafts [59,61–66]. Several studies, however, have demonstrated that doses
less than 2.5 Mrad have no effect on ACL reconstruction [32,67]. Because of
the detrimental effects of high-dose gamma irradiation on allograft tissue, it
CLINICAL OUTCOMES OF ALLOGRAFT VERSUS AUTOGRAFT 673
revascularization and migration of host fibroblasts into the graft tissue, typically
begins within 20 days of surgery, and may continue throughout the first
6 months following surgery [52,91,94,97,98]. During this phase of graft matu-
ration, changes occur in the material properties of the graft. Graft strength may
drop to as low as 11% of the normal ACL during this phase [95], emphasizing
the need for protected rehabilitation during this period. During the final phase
of graft healing, the graft undergoes maturation and remodeling. The microvas-
cularity, cellular population, and collagen bundle orientation in the replace-
ment tissue matures fully to a nearly normal ACL appearance within 12 to
18 months postoperatively [94,99–102]. The biomechanical properties of the
graft material also improve during the final phase of remodeling but do not re-
cover to the initial stiffness and strength of the material at the time of implan-
tation [91,93,95,103].
Healing of the graft material to the tunnel wall is another important consider-
ation when evaluating graft choices. Bone-to-bone healing, as occurs with BPTB
grafts, is relatively quick, with incorporation into the host bone often seen by 6
weeks. Soft tissue-to-bone incorporation takes considerably longer, often taking
8 to 12 weeks to mature [96]. Additionally, incorporation of allograft tissue oc-
curs at a slower rate than autograft tissue. Jackson and colleagues [93] found,
in a goat model, that allograft BPTB grafts demonstrated a prolonged inflamma-
tory stage, smaller cross-sectional area, delayed remodeling of collagen fibers,
and decreased mechanical strength for the first 6 months after reconstruction.
Zhang and colleagues [104] demonstrated, in a dog soft tissue reconstruction
model, that at 6 months the maturation of the insertional bone–tendon interface
was delayed in allograft tissue in comparison with autograft tissue. Nikolaou and
colleagues [105], however, found, in a dog model, that by 24 weeks autograft and
allograft tissue had nearly normal revascularization and by 36 weeks the mechan-
ical properties of autograft and allograft tissue were similar and had approached
90% of the control ligament strength. Shino and colleagues [100] and Yamagishi
and colleagues [106] found that mature revascularization takes 18 months to oc-
cur for both autograft and allograft ACL reconstruction. These differences in
graft incorporation and maturation between bone and soft tissue grafts and be-
tween autograft and allograft may be important factors to consider when deter-
mining rehabilitation criteria and timing for return to play.
SUMMARY
ACL reconstruction is one of the procedures most commonly performed by
sports medicine physicians today. Good-to-excellent results in terms of knee
stability, patient satisfaction, and return to athletic activity are reported com-
monly to be around 90% [107]. Although BPTB grafts traditionally have
been considered the reference standard, donor-site morbidity has led to an in-
terest in alternative graft choices. Commonly used autograft options to BPTB
include hamstring tendons and, to a far lesser extent, quadriceps tendon grafts.
Allograft options include BPTB, Achilles tendon, anterior and posterior tibialis
grafts, hamstring tendons, and fascia lata grafts. With successful clinical
676 BAER & HARNER
outcomes achieved with both autograft and allograft tissues, the choice of graft
material becomes one of surgeon and patient preference. Autograft tissue offers
the advantages of no risk of disease transmission, a high success rate, and no
immunogenic response. These benefits must be balanced with donor-site mor-
bidity, difficulty of graft harvest, additional operating room time associated
with graft harvest, and the limits and unpredictability in graft size and quality.
Allograft tissue has the advantages of lacking donor-site morbidity, smaller in-
cisions, decreased operative time, easier and less painful rehabilitation, and
larger and more predictable graft sizes. The major disadvantage of allograft re-
construction is the risk of disease transmission; although with current screening,
processing, and sterilization techniques the risk is extremely low, it should not be
overlooked. Additionally, when using allograft tissue, one must be aware that al-
lograft tissue may generate a low-level immune response. It also has been shown
to have delayed incorporation time, and the cost for the allograft tissue itself is
greater. Overall, no graft choice can match completely the characteristics and
function of the native ACL. The ideal graft choice should have biomechanical
properties similar to those of the native ACL, have low morbidity, incorporate
quickly, and be able to restore functional stability to the knee over the long
term while taking into account individual patient factors, including patient pref-
erence, activity level, prior surgery, comorbidities, and goals.
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