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

Abstract

Background: Chronic degeneration of rotator cuff tendons is a major contributing factor to the unacceptably high prevalence of rotator cuff repair surgery failures. The etiology of chronic rotator cuff degeneration is not well understood, and current therapies are not effective, necessitating preclinical research to fill this knowledge gap. Unfortunately, current large animal models rely on enthesis disruption as a means of model generation, which is not representative of human patients with chronic rotator cuff degeneration prior to full-thickness tears. Following, the goal of this study was to develop and characterize a translational large-animal model of chronic rotator cuff degeneration without enthesis release.Methods: A midsubstance damage model [i.e., "combed fenestration" (CF)] in adult sheep was generated by creating 16 longitudinal cuts within the top third of the infraspinatus tendon thickness. Tendon integrity was characterized through exhaustive non-destructive biomechanical stress relaxation testing [peak stress, peak load, percent relaxation, and cross-sectional area (CSA)], followed by histopathological degeneration scoring and analysis (Bonar score), histomorphological analysis of collagen organization and fatty atrophy (percent adipose area), and gene expression analyses.Results: The CF model tendons exhibited significantly decreased mechanical properties as evidenced by decreased peak stress (P<0.025) and increased percent relaxation (18-week vs. Control, P<0.035) at multiple strain magnitudes and across all timepoints. At all timepoints, the CF tendons exhibited pathological changes aligned with tendon degeneration, as evidenced by increased Bonar scoring (P<0.001) and decreased collagen organization (6-week vs. Control, p=0.013). Increases in intramuscular adipose content were also documented through histomorphology analysis (6-week and 18-week vs. Control, P<0.077). Significant changes in gene expression were noted at all timepoints.Conclusions: These data reveal that this new ovine CF model of chronic rotator cuff degeneration results in tendons with decreased mechanical properties, degenerative pathology characteristics, and gene expression profiles that aligned with the degenerative changes that have been noted in humans with tendinopathy. For these reasons, we believe this novel large animal model of chronic rotator cuff degeneration is a translational platform in which to test devices, therapies, and/or technologies aimed at repairing damage to the shoulder.

Biomechanical and histological changes secondary to aging in the human rotator cuff: A preliminary analysis

“…Following tendon isolation, the humerus was mounted (SmoothCast 321, Smooth‐On) within a potting sleeve to allow for biomechanical testing 20,21 . This potting sleeve was installed in a custom fixture to ensure tendon testing occurred in anatomically appropriate directions (i.e., aligned with the natural direction of loading) on the servo‐hydraulic load frame (Model 858, MTS Corp.).…”

“…The presence of intramuscular adipose content has long been correlated with decreased RCR outcomes and increased degenerative tendon pathology 34 . As such, the intramuscular adipose content within the rotator cuff muscle groups was quantified using histomorphometry techniques, 21 with the intention of correlating changes to tendon biomechanical properties at different stages of associated muscle fatty atrophy. Adipose area and total tissue area were quantified (Image‐Pro Premier v9.2, RRID:SCR_007369).…”

“…Following tendon isolation, the humerus was mounted (SmoothCast 321, Smooth-On) within a potting sleeve to allow for biomechanical testing. 20,21 This potting sleeve was installed in a custom fixture to ensure tendon testing occurred in anatomically appropriate directions (i.e., aligned with the natural direction of loading) on the servohydraulic load frame (Model 858, MTS Corp.). The tendons were gripped using a custom cryo-grip maintained between −10°C and −15°C, and a warm physiologic saline spray was used to ensure no tendon freeze artifact while ensuring adequate gripping strength.…”

Modified Alendronate Mitigates Mechanical Degradation of the Rotator Cuff in an Osteoporotic Ovine Model

“…As outlined previously, 19,20 H&E slides were graded by the pathologist using the semiquantitative Bonar tendinopathy scale, which is designed to quantify pathological characteristics of tendinopathy. 7,13 Samples were assessed for (1) tenocyte reactivity, (2) angiogenesis, (3) tendon bundle organization and polarization, and (4) deposition of ground substance.…”

“…A machine learning algorithm (Version 9.2; Image-Pro Premier) was programmed to calculate percentage area of the organized/disorganized collagen seen within the analytic region within the tendon. 19,20 The region of analysis included the most proximal 25 mm of tendon but did not include the fibrocartilaginous enthesis zone.…”