Experiences with sheep as an animal model for shoulder
surgery: Strengths and shortcomings
A. Simon Turner, BVSc, MS, Dipl ACVS, Ft. Collins, CO
Sheep (and goats) are a convenient large-animal
model for rotator cuff repair because of availability,
ease of handling and housing, animal cost, and acceptance to society as a research animal. Tenotomy of
the infraspinatus tendon and subsequent reattachment
to the proximal humerus is useful to address the biomechanical, histologic, and biochemical processes of rotator cuff repair. Detaching this tendon and immediately reattaching it does not represent the clinical
picture but serves as a relatively rapid way to screen
different suture anchors, suture patterns, scaffolds,
growth factors, and other biologics or a combination
of these treatments to enhance the healing process. To
minimize spontaneous reattachment and reproduce a
chronic rotator cuff injury, the end of the tendon can
be covered and then reattached 4 weeks later if boneto-tendon healing is to be evaluated. This chronic
model is useful to understand the biology (degree of
muscle atrophy and fatty infiltration) of rotator cuff
muscles as well as innovative methods of repair.
Close-stall confinement is required during the convalescence in acute and chronic studies. Ultrasound in the
awake animal can be used to monitor gap formation
and tissue organization. Sheep have also been used
to determine whether capsular healing after plication
is equivalent to open capsular shift. (J Shoulder Elbow
Surg 2007;16:158S-163S.)
S keletally mature female sheep are rapidly becom-
ing a convenient large-animal model for a variety of
orthopedic problems, including rotator cuff repair.18
This is because of availability, ease of handling and
housing, animal cost, and acceptance to society as a
research animal. Although the anatomy of the shoulder of quadrupeds is quite different than humans,
From the Department of Clinical Sciences, Veterinary Medical
Center, Colorado State University.
Reprint requests: A. Simon Turner, BVSc, MS, Dipl ACVS, Professor, Department of Clinical Sciences, Veterinary Medical Center,
Colorado State University, Ft. Collins, CO 80523 (E-mail:
[email protected]).
Copyright © 2007 by Journal of Shoulder and Elbow Surgery
Board of Trustees.
1058-2746/2007/$32.00
doi:10.1016/j.jse.2007.03.002
158S
tenotomy of the infraspinatus of goats17 and sheep,5
and subsequent reattachment to the proximal humerus, is useful to address the biomechanical, histologic, and biochemical processes of rotator cuff repair.
Sheep have been selected because the similarity of
the infraspinatus tendon to the human supraspinatus
tendon.3 Although the sheep infraspinatus tendon is
not intraarticular, there is a bursa under the tendon,
and therefore, the repair has some contact with synovial fluid that lubricates the bursa. The bursa likely
does not have the volume of synovial fluid that is
contained in the shoulder joint. Therefore, the repaired tendon has some characteristics of a healing
tendon in a milieu of synovial fluid. In most cases,
retrieval surgery harvests robust tendon-like scar material that forms between the retracted tendon stump
and the bone (gap scar formation). This is not analogous to the human condition in which gaping or
failure to heal occurs in rotator cuff repair.
This tendon also useful for in vitro studies2,10 because it is relatively easy to prepare for biomechanical testing owing to its size. Surgery on one shoulder
is well tolerated in sheep. The Institutional Animal
Care and Use Committee (IACUC) may only allow the
surgery to be performed on one forelimb, but some
IACUC’s may allow both. Preemptive and postoperative analgesia is essential to all animal studies.
SURGICAL APPROACH
Shoulder surgery in sheep is performed under general anesthesia with the animal in lateral recumbency.
An open approach to the shoulder is used because
arthroscopic repair would be impractical. A gently
curving skin incision is made over the point of the
shoulder and then deepened through the subcutaneous tissues. The skin is reflected and the fascia of the
brachialis muscle is incised. The acromial head of the
deltoideus muscle will become visible. A plane of
dissection is established along the cranial edge of the
deltoideus muscle and the muscle reflected caudad.
Important anatomic structures of the shoulder joint
in sheep are displayed in Figure 1. The insertion of
the infraspinatus tendon is identified, and a curved
forceps placed under the tendon. The tendon is
incised along its attachment to the greater tuberos-
J Shoulder Elbow Surg
Volume 16, Number 5S
Turner
Figure 1 A, Intraoperative view of the surgical approach to the right tendinous insertion of the infraspinatus muscle
in the sheep. The acromial head of the deltoideus muscle is retracted. B, Anatomic dissection of a right shoulder
shows the location of M. terres minor. C, Further dissection of a right shoulder shows the synovial bursa and the
footprint of M. infraspinatus. D, Deeper dissection of a right shoulder shows the humeral head and joint capsule.
E, Bony anatomic landmarks of the right sheep shoulder.
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Figure 2 Reattachment of the infraspinatus tendon of the sheep
using modified Mason-Allen suture pattern and a bone trough.
J Shoulder Elbow Surg
September/October 2007
Figure 3 Deployment of suture anchors in the dense bone of the
lateral epicondyle of the humerus on sheep.
ity of the humerus (Figure 1, A and B). The footprint
of the tendon is approximately 10 mm ⫻ 20 mm
(Figure 1, C). Immediately under the tendon is a
synovial bursa that does not communicate with the
shoulder joint (Figure 1, C). The shoulder joint is not
entered in this approach (Figure 1, D).
At this point, a Hall air drill and burr are used to
create a bed of bleeding bone, and if a bone trough
is to be used, it is prepared at this stage. Orthopedists
new to this model will be surprised and pleased at
how dense sheep bone is compared with adult or
elderly human bone. Predrilling of the bone is necessary for suture anchor insertion. Acute and chronic
studies of infraspinatus reattachment will be discussed.
ACUTE STUDIES
Clearly, detaching the ovine (or caprine) infraspinatus tendon and immediately reattaching it does not
represent the clinical picture. It does, however, serve
as a relatively rapid way to screen different suture
anchors, suture patterns, scaffolds, growth factors,
and other biologics, or a combination of these treatments, to enhance the healing process (Figure 2). Survival times frequently used are 6 and 12 weeks.
Group sizes are typically 12 animals if mechanical
testing and histology are end points. Within each
group, 9 animals are allocated to mechanical testing
and 3 for histology.
Some of the earlier studies using sheep (and goats)
have evaluated different methods of tendon reattachment. St. Pierre el al,17 used goats to evaluate tendon
healing to cortical bone compared with a cancellous
trough. They evaluated the repairs histologically and
biomechanically and found the tendon-to-bone healing process quite similar.
Figure 4 Low-intensity pulsed ultrasound treatment after immediate reattachment of the infraspinatus.12,13 Other large animal
models (including goats) compared with sheep, would not tolerate
the harness shown.
Other acute studies using sheep have looked at
different suture anchors (Figure 3),6 a mixture of bone
morphogenetic proteins,15 suture patterns,5,9 lowintense pulsed ultrasound (Figure 4)12,13 and swine
small intestinal submucosa.16
CHRONIC STUDIES
The repair of a chronic, massive, rotator cuff injury
is a challenge to the shoulder surgeon. This has
prompted the search for a clinically relevant animal
model to evaluate methods to enhance repair and
understand the biology behind the chronic tear. Initially, delayed repair of the released infraspinatus
tendon was not recommended because of the difficulty in distinguishing scar tissue from normal tendon
J Shoulder Elbow Surg
Volume 16, Number 5S
Figure 5 Identification of the infraspinatus tendon covered with
Gore-Tex (PRECLUDE, W. L. Gore & Associates, Flagstaff, AZ) in a
chronic model.1
at the time of reattachment.5 As a rule, animals are
known to heal rapidly, with abundant neovascularization and fibrous tissue ingrowth; sheep are no
exception.
In later studies, methods to cover the end of the
ovine infraspinatus and minimize spontaneous reattachment were refined. To reproduce a chronic rotator cuff injury, Coleman et al1 covered the end of the
infraspinatus with Gore-Tex (PRECLUDE; W. L. Gore
& Associates, Flagstaff, AZ; Figure 5). The sheep
were reoperated on 6 weeks later. The PRECLUDEcovered tendon was located, isolated, and reattached to the lateral tuberosity of the humerus. The
tendon had retracted an average of 2.6 cm (range,
1.9-2.9). In that study, some sheep were reoperated
on at 18 weeks. These animals had irreparable tendons because of excessive retraction, which were
secured using a synthetic scaffold as a bridge.
To aid in identification of the detached infraspinatus tendon after long periods of detachment, Gerber
et al4 performed an osteotomy of the greater tuberosity of the humerus. To prevent spontaneous healing,
the end of the tendon was covered with a 5-cm-long
silicone rubber tube. They also found fatty infiltration
and muscle atrophy in proportion to the amount of
musculotendinous retraction. Therefore, the chronic
detachment model in sheep is also useful to understand the biology (degree of muscle atrophy and fatty
infiltration) of rotator cuff muscles as well as innovative methods of repair. The chronic model gives the
surgeon a better understanding of the timing of the
repair and the temporal aspects of healing.1,4,11
These long-standing chronic models (detached for
periods greater than 8 weeks) are more useful to
evaluate bioimplants (eg, collagen scaffolds) rather
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than attempted reattachment to the bone. In sheep, we
currently recommend infraspinatus detachment and covering, and then reattachment, as soon as 4 weeks if
bone-to-tendon healing is to be evaluated. If the ability
of a bioimplant, scaffold, autologous platelet-rich fibrin
matrix, a growth factor or a combination of these to
bridge a large gap is to be evaluated, the reattachment surgery can be scheduled 8 weeks after the
detachment and covering surgery.
Some of the earlier problems using the sheep
model of rotator cuff repair were related to suture
rupture caused by failure to protect the repair from full
weight bearing. Because slinging was poorly tolerated in sheep and not permitted by our IACUC, a
rubber ball was placed under the hoof of the involved
limb to see if this restricted limb movement, and this
was removed at 5 weeks.8
Lewis et al8 looked at the effect of immobilization
on infraspinatus healing using a modified MasonAllen suture. They found that that there was no difference between the treatment groups for load-to-failure
and stiffness, so this cannot be recommended as a
method of immobilization. Rather, we have reverted
to close-stall confinement during the convalescence.
In summary, it is virtually impossible to control the
postoperative loads on the repaired tendon, and
there are no data to suggest that the ball on the hoof
actually leads to diminished weight bearing. Furthermore, other researchers with experience with this
model suggest that the sheep fires the muscles as it
resists and “fights” the ball on the hoof. Therefore, this
is not a method to “immobilize” the repaired shoulder. Because sheep and goats are large, heavy animals, they likely fire the shoulder girdle muscles immediately on standing up after surgery.
The high loads imposed by weight-bearing result in
some separation of the repair in this model. The gap
between the distal end of the transected tendon and
the proximal humerus can be identified on the ultrasound images in the awake but restrained sheep,
without costly general anesthesia, to monitor progression or lack of healing (Figure 6).
Although many of these repairs fail to heal by
tendon-to-bone healing, the model is still useful to
study the effect of chronic tendon detachment on
muscle atrophy and fatty infiltration. The model can
also be used to study the effect of various devices and
factors on decreasing the rate of healing of primary
repairs for them to remain intact or the biologic effects
on the formation and maturation of tendon-like scar
formation in a preclinical model using a rotator cuff
surgical site.
Other issues with this model that should be mentioned are that the forelimb is weight bearing and
there is no clavicle, a less-developed acromion, and
no coracoacromial arch. These differences between
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J Shoulder Elbow Surg
September/October 2007
Figure 6 Monitoring healing with ultrasound images of the right shoulder in the awake sheep after reattachment
of the infraspinatus tendon with gap formation (left) and organized tissue (right).
the sheep (goat) and humans are probably not as
important as the issue mentioned above.
An important factor related in this, and likely other
large-animal models, is that all of the repairs detach
to some degree. The intervening gap fills in with
fibrous scar tissue, unlike humans where a gap typically forms, which may be due to the extraarticular
nature of the repair. As a result, this is a model of
tissue formation in a gap. As such, the model may
have real advantages as a “tissue engineering” approach to tissue formation, but likely it does not
evaluate direct healing between tendon and bone.
One distinct disadvantage of the model is a lack of
species-specific probes and reagents for sheep (eg,
antibodies), which limits the ability to conduct detailed histologic analyses such as immunohistochemistry and in-situ hybridization.
Figure 7 Plication of the shoulder joint capsule in the sheep.7
GLENOHUMERAL INSTABILITY ASSESSMENT
The shoulder of the sheep can be used to evaluate
the response of the glenohumeral joint capsule. Obrzut et al14 used explanted sheep shoulders to evaluate the effect of radiofrequency energy on the length
and temperature properties of the capsule. Sheep
have been used to determine whether capsular healing after plication is equivalent to open capsular shift
(Figure 7).7 As determined from histologic appearance, there was no difference in the 2 techniques.
and economic large-animal model for various therapies of the shoulder joint, particularly the enhancement of bone-to-tendon healing. In addition, researchers are continuing to refine the model and learn more
about its limitations. Studies of growth factors at different doses and stem-cell therapy, in combination
with different scaffold materials and their configurations, are likely to dominate this exciting field of
orthopedic research.
SUMMARY
REFERENCES
Research facilities around the world are continuing
to gain more experience with sheep as a practical
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DW, Warren RF, et al. Chronic rotator cuff injury and repair
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