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).
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%.
|Richardson, William J; Kegerreis, Brian; Thomopoulos, Stavros et al. (2018) Potential strain-dependent mechanisms defining matrix alignment in healing tendons. Biomech Model Mechanobiol :|
|Shah, Shivam A; Kormpakis, Ioannis; Cavinatto, Leonardo et al. (2017) Rotator cuff muscle degeneration and tear severity related to myogenic, adipogenic, and atrophy genes in human muscle. J Orthop Res 35:2808-2814|
|Genin, Guy M; Thomopoulos, Stavros (2017) The tendon-to-bone attachment: Unification through disarray. Nat Mater 16:607-608|
|Deymier, Alix C; Nair, Arun K; Depalle, Baptiste et al. (2017) Protein-free formation of bone-like apatite: New insights into the key role of carbonation. Biomaterials 127:75-88|
|Abraham, Adam C; Shah, Shivam A; Thomopoulos, Stavros (2017) Targeting Inflammation in Rotator Cuff Tendon Degeneration and Repair. Tech Shoulder Elb Surg 18:84-90|
|Shah, Shivam A; Kormpakis, Ioannis; Havlioglu, Necat et al. (2017) Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model. J Bone Joint Surg Am 99:855-864|
|Lipner, Justin; Shen, Hua; Cavinatto, Leonardo et al. (2015) In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber Scaffold for Tendon-to-Bone Repair. Tissue Eng Part A 21:2766-74|
|Killian, Megan L; Cavinatto, Leonardo M; Ward, Samuel R et al. (2015) Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats. Am J Sports Med 43:2401-10|
|Sato, Eugene J; Killian, Megan L; Choi, Anthony J et al. (2015) Architectural and biochemical adaptations in skeletal muscle and bone following rotator cuff injury in a rat model. J Bone Joint Surg Am 97:565-73|
|Thomopoulos, Stavros; Parks, William C; Rifkin, Daniel B et al. (2015) Mechanisms of tendon injury and repair. J Orthop Res 33:832-9|
Showing the most recent 10 out of 20 publications