Animal model studies provide insight for clinical treatment
The great apes may be man’s closest animal relatives, but it’s the rat that may teach us the most about rotator cuff disease, according to Louis J. Soslowsky, PhD, this year’s winner of the Kappa Delta Ann Doner Vaughan award. In a series of studies using the rat model, Dr. Soslowsky has demonstrated the impact of extrinsic factors on overuse injuries and the importance of postsurgical activity levels in the healing response.
Louis J. Soslowsky, PhD
After his appointment to the faculty of the University of Michigan in 1991, he began to focus on developing an animal model that could be used to address injury and repair mechanisms of injury, studies that he continued after he moved to the University of Pennsylvania in 1997.
Meeting the criteria
Dr. Soslowsky first needed to identify an animal model with a shoulder that would correspond to human anatomy and functionality in the most critical features so that he could use it to test his hypotheses and further his studies. He developed a 34-item checklist, paying particular attention to the relationship between the rotator cuff and its surrounding structures. After investigating 32 animal species, Dr. Soslowsky noted that “the rat was the only one that satisfied all 34 criteria.”
In particular, “the rat has a prominent supraspinatus tendon, which inserts on the greater tuberosity of the proximal humerus as it does in the human.” Another important anatomic structure in humans—an arch formed by the coracoid, the acromion, and the coracoacromial ligament—is mirrored in the rat, which also has an enclosed arch formed by the coracoid, the clavicle, the acromion, and their connecting ligaments (Fig. 1).
In addition to the anatomic similarities, Dr. Soslowsky noted functional parallels that supported the conclusion that “positions and activities believed to cause rotator cuff disease in the human are commonly achieved in the rat.”
In a series of subsequent studies, Dr. Soslowsky was able to evaluate the effects of overuse on tendons. He measured the effects of an overuse running regime in the rat that paralleled the training regime of an elite human swimmer and found that the mechanical properties of the tendons deteriorated as they became hypertrophied. He also noted increases in cellularity, increases in collagen disorganization, and changes in cell shape, particularly in tendons that were also subjected to either an intrinsic injury or extrinsic compression as well as overuse.
His search for an early marker in the injury process found that the supraspinatus tendon increased expression of cartilage genes, suggesting that repetitive loading and repeated compression on the tendon may affect the very constituent makeup of the tendon itself.
Dr. Soslowsky’s team also studied the healing processes. By surgically creating a defect in the tendon, and then freezing and thawing the adjacent tissue in rats, the team was able to compare the healing response between normal and intrinsically damaged tendons. They found no significant differences between the two groups, indicating an active but inadequate repair response even in normal tissue. “This model has application toward the study of techniques to improve or accelerate cuff defect healing,” said Dr. Soslowsky. A follow-up study examining the effect of adding a fibrin clot found no benefits from the addition of the clot.
Subsequent studies examined the effects of various postoperative activity protocols on tendon-to-bone healing. One study compared immobilization, cage (limited) activity, and exercise. Although activity level did not affect structural properties, it did result in significant biomechanical changes. “More material of lesser quality is produced when activity level is increased,” according to Dr. Soslowsky.
Surgery to repair injury to the rotator cuff will result in reduced range of motion, but immobilization after surgery will not result in permanent loss of motion or increase in joint stiffness. “Because immobilization does improve the repair properties at the insertion site where repairs often fail, immobilization should be considered in the postsurgical management of rotator cuff tears,” said Dr. Soslowsky.
Additionally, his research shows that early passive motion during immobilization is detrimental to shoulder mechanics; when or whether passive motion should start is a subject that is still being investigated.
Early repair, however, is supported by Dr. Soslowsky’s findings. “Repair tension—the force required at repair to reappose the tendon to its original insertion site on the humerus—rapidly increases after the injury, followed by a progressive, but less dramatic, increase with additional time. These findings suggest that rotator cuff tears should be repaired early, when possible, in the clinic.”
Dr. Soslowsky is well aware of the clinical applications that may result from his research. “Based on the fundamental nature of the information obtained to date, future investigations, by my team and by others, are now poised to investigate true mechanisms of injury and healing at the molecular, cellular, and tissue level in this and other model systems,” he said. “We plan to continue this important basic science and clinically relevant research to address this common and disabling problem.”
Dr. Soslowsky will present his award-winning paper on Tuesday, March 9, in Auditorium A of the Morial Convention Center, as part of the Orthopaedic Research Society Annual Meeting; the Kappa Delta Ann Doner Vaughan Award will be presented during the Opening Ceremonies of the AAOS Annual Meeting, on Wednesday, March 10, in the La Nouvelle Ballroom, Morial Convention Center. He reports no conflicts of interest for this research.
Mary Ann Porucznik is managing editor of AAOS Now. She can be reached at email@example.com
- The anatomic structures and functional operations of the rat shoulder parallel those in humans, making the rat an excellent model for studying rotator cuff disease and healing.
- Etiologic factors, such as overuse and injury, can trigger detrimental changes in the supraspinatus tendon; as these changes are identified using a rat model, new therapeutic approaches and treatment modalities may be developed for humans.
- Immobilization after surgery to repair the rotator cuff does not result in permanent loss of motion or an increase in joint stiffness; in addition, early passive motion may be detrimental to rotator cuff tendon to bone healing.