Optimizing Tissue Engineering for Clinical Relevance in Rotator Cuff Repair

Rotator cuff tear (RCT) is the most common cause of disability in the upper extremity. It results in 4.5 million physician visits in the United States every year and is the most common etiology of shoulder conditions evaluated by orthopedic surgeons. Over 460,000 RCT repair surgeries are performed in the United States annually. Rotator cuff (RC) retear and failure to heal remain significant postoperative complications. Literature suggests that the retear rates can range from 29.5% to as high as 94%. Weakened and irregular enthesis regeneration is a crucial factor in postsurgical failure. Although commercially available RC repair grafts have been introduced to augment RC enthesis repair, they have been associated with mixed clinical outcomes. These grafts lack appropriate biological cues such as stem cells and signaling molecules at the bone-tendon interface. In addition, they do little to prevent fibrovascular scar tissue formation, which causes the RC to be susceptible to retear. Advances in tissue engineering have demonstrated that mesenchymal stem cells (MSCs) and growth factors (GFs) enhance RC enthesis regeneration in animal models. These models show that delivering MSCs and GFs to the site of RCT enhances native enthesis repair and leads to greater mechanical strength. In addition, these models demonstrate that MSCs and GFs may be delivered through a variety of methods including direct injection, saturation of repair materials, and loaded microspheres. Grafts that incorporate MSCs and GFs enhance anti-inflammation, osteogenesis, angiogenesis, and chondrogenesis in the RC repair process. It is crucial that the techniques that have shown success in animal models are incorporated into the clinical setting. A gap currently exists between the promising biological factors that have been investigated in animal models and the RC repair grafts that can be used in the clinical setting. Future RC repair grafts must allow for stable implantation and fixation, be compatible with current arthroscopic techniques, and have the capability to deliver MSCs and/or GFs.