The rotator cuff muscles of the shoulder provide stability and motion at the glenohumeral joint. Rotator cuff disease is a degenerative condition that leads to significant shoulder pain, muscle atrophy, and tendon rupture, severely limiting upper extremity function. Rotator cuff repair to treat shoulder pain and restore strength is one of the most common orthopedic surgical procedures, however, rotator cuff tendon healing is unpredictable, with short to midterm failure rates ranging from 30- 94%. The majority of rotator cuff disease is related to chronic degeneration of the cuff tissues. Degenerative changes can lead to massive, irreparable rotator cuff tears through attritional changes in the tendons and irreversible fatty degeneration of the rotator cuff muscles. To date, most rotator cuff experimental studies have used acute injury and repair animal models (i.e., a healthy muscle and tendon is injured and then immediately repaired). These studies, while valuable, are only relevant to a small percentage of the rotator cuff cases seen clinically. In this proposal we seek to examine rotator cuff degeneration and repair using our newly developed, clinically relevant, animal model of rotator cuff disease. Understanding the process of rotator cuff degeneration and the potential for a degenerated cuff to heal will greatly enhance the clinician's ability to treat rotator cuff disease. Musculoskeletal tissues are highly sensitive to their mechanical environment. Clinical and experimental studies support the idea that decreased loading, either through tendon injury or denervation, leads to muscle and tendon degeneration. Rotator cuff tendon tears unload the rotator cuff muscles, leaving them vulnerable to deterioration and ultimately a chronically degenerated, irreparable rotator cuff. With regard to rotator cuff repair, the role of mechanical loading is more complex. In acute rotator cuff repairs, protective immobilization is beneficial to healing but complete removal of loading is detrimental to healing. Understanding the role of the mechanical environment for rotator cuff degeneration and repair of chronically degenerated cuffs will allow us to propose rehabilitation strategies to maximize muscle recovery and improve healing after surgical repair. Therefore, the overall objective in this study is to examine the role of the mechanical environment on rotator cuff degeneration and healing. Our approach will use a rat rotator cuff animal model to study cuff degeneration (Aim 1) and repair (Aims 3 and 4). We will compare results in our animal model to clinical data to validate that our basic science studies are relevant to the human condition (Aim 2).

Public Health Relevance

The rotator cuff muscles of the shoulder provide stability and motion at the glenohumeral joint. Rotator cuff disease is a degenerative condition that leads to significant shoulder pain, muscle atrophy, and tendon rupture, severely limiting upper extremity function. Rotator cuff repair to treat shoulder pain and restore strength is one of the most common orthopedic surgical procedures, with over 75,000 repairs performed each year in the United States. However, rotator cuff tendon healing is unpredictable, with short to midterm failure rates ranging from 30- 94%.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AR057836-05
Application #
8698275
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Sato, Eugene J; Killian, Megan L; Choi, Anthony J et al. (2014) Skeletal muscle fibrosis and stiffness increase after rotator cuff tendon injury and neuromuscular compromise in a rat model. J Orthop Res 32:1111-6
Killian, Megan L; Cavinatto, Leonardo; Shah, Shivam A et al. (2014) The effects of chronic unloading and gap formation on tendon-to-bone healing in a rat model of massive rotator cuff tears. J Orthop Res 32:439-47
Swan, Malcolm A; Sato, Eugene; Galatz, Leesa M et al. (2014) The effect of age on rat rotator cuff muscle architecture. J Shoulder Elbow Surg 23:1786-91
Lu, Helen H; Thomopoulos, Stavros (2013) Functional attachment of soft tissues to bone: development, healing, and tissue engineering. Annu Rev Biomed Eng 15:201-26
Killian, M L; Lim, C T; Thomopoulos, S et al. (2013) The effect of unloading on gene expression of healthy and injured rotator cuffs. J Orthop Res 31:1240-8
Killian, Megan L; Cavinatto, Leonardo; Galatz, Leesa M et al. (2012) The role of mechanobiology in tendon healing. J Shoulder Elbow Surg 21:228-37