The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears

Abstract

The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

Keywords: developmental engineering; enthesis; mechanobiology; rotator cuff.

FIG. 1.

The effect of chronic, massive tears on the elements of the rotator cuff organ. The native enthesis (A) contains a complex structure that is not restored following surgical repair (B); instead of a gradient in mineral content and interpositional fibrocartilage, the repaired tendon abruptly adjoins bone. The black arrow indicates the suture hole. As shown with micro-computed tomography, the humeral head of uninjured or acutely repaired rotator cuff tears (C) exhibit superior bone quality (e.g., bone mineral density) to the humeral heads of chronically torn rotator cuff tendons (D). Adapted with permission from Killian et al. Native muscle fibers are polygonal with peripheral nuclei (E) whereas degenerated muscle in the context of chronic tears undergoes atrophy, fibrosis, and fatty infiltration (F). Lastly, uninjured tendon consists of fibroblasts (arrow heads) elongated in the direction of aligned collagen fibrils (G). With chronic degeneration, collagen fibrils become disorganized and delaminated (arrow heads), with concurrent heterotopic cartilage formation (H). Black arrows indicate chondrocyte-like cells. Adapted with permission from Buck et al.

FIG. 2.

The role of hedgehog signaling in enthesis formation and healing. Parallel columns of fibrochondrocytes are embedded in a proteoglycan-rich extracellular matrix (A) that has undergone robust mineralization (C) by postnatal day 42 in the developing rotator cuff enthesis of a mouse, as shown through Safranin O (A, B) and Von Kossa (C, D) staining, respectively. Conditional ablation of Hh-responsive cells disrupts enthesis formation with reductions in proteoglycan (B) and mineral content (D, black arrow). Adapted with permission from Schwartz et al. Cells located at the native ACL–bone interface in a mature rat do not strongly express Hh mediators (E). Conversely, Hh signaling is strongly upregulated in cells at the tendon graft–bone tunnel interface following ACL reconstruction (F). Focal stresses appear to differentially affect Hh signaling and tissue organization (G), as interfaces presumably under greater tension (bottom, black arrows) exhibit greater organization and fibrochondrocyte alignment than unloaded interfaces (G, white arrows). ACL, anterior cruciate ligament; B, bone; Hh, hedgehog; IF, interface; T, tendon. Adapted with permission from Carbone et al.