Enthesis trauma as a means for the development of translatable chronic rotator cuff degeneration in an ovine model

James Johnson; Devin von Stade; Daniel Regan; Jeremiah Easley; Lyndah Chow; Steven Dow; Tony Romeo; Ted Schlegel; Kirk McGilvray

doi:10.21037/atm-21-354

Enthesis trauma as a means for the development of translatable chronic rotator cuff degeneration in an ovine model

Ann Transl Med. 2021 May;9(9):741. doi: 10.21037/atm-21-354.

Authors

James Johnson¹, Devin von Stade¹, Daniel Regan², Jeremiah Easley³, Lyndah Chow⁴, Steven Dow^{2

4}, Tony Romeo⁵, Ted Schlegel⁶, Kirk McGilvray¹

Affiliations

¹ Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, CO, USA.
² Flint Animal Cancer Center and Department of Microbiology, Immunology, & Pathology, CSU Flint Animal Cancer Center, Fort Collins, CO, USA.
³ Preclinical Surgical Research Laboratory, Colorado State University, Fort Collins, CO, USA.
⁴ Department of Clinical Sciences, Center for Immune and Regenerative Medicine, Colorado State University, Ft. Collins, CO, USA.
⁵ Rothman Orthopaedic Institute, New York, New York, USA.
⁶ Department of Orthopedics/University of Colorado School of Medicine, Aurora, CO, USA.

Abstract

Background: Untreated rotator cuff tears lead to irreversible tendon degeneration, resulting in unacceptable repair prognosis. The inability of current animal models of degenerated rotator cuff tendons to more fully emulate the manifestation and degree of pathology seen in humans with a previously torn rotator cuff tendon (s) significantly impairs the development of novel therapeutics. Therefore, the objective of this study was to develop a large-animal translational model of enthesis damage to the rotator cuff tendons to mimic the chronic degenerative changes that occur in patients that demonstrate clinical manifestations of tendinopathy.

Methods: A partial enthesis tear model (i.e., sharp transection) in adult sheep was created by cutting the tendon fibers perpendicularly through the enthesis midpoint, while leaving the other portion of the tendon in-tact. To assess tendon integrity, non-destructive biomechanical tests were performed, followed by histopathological, histomorphological, and gene expression analysis. Samples of degenerated human rotator cuff tendons obtained from patients undergoing reverse total shoulder arthroplasty to use for comparative pathological analysis.

Results: In the sheep model, transected tendons at all timepoints had significantly decreased mechanical properties. Histopathologic evaluation and Bonar scoring revealed that the tendons in sheep underwent degenerative changes similar in magnitude and manifestation as the degenerated human tendon samples. Furthermore, similar levels of collagen disorganization were noted between the 6 and 12-week ovine samples and the degenerated human samples.

Conclusions: These findings indicate that the new sheep model of rotator cuff injury reliably recapitulates the structural and cellular changes that occur clinically in humans with chronic rotator cuff tendon injuries and suggest that this new model is well suited to evaluation of new therapeutic interventions.

Keywords: Rotator cuff; biomechanics; chronic degeneration; gene expression; histopathology.

Abstract

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