The path from injury to degeneration: multi-modal characterization of chronic rotator cuff degeneration
Date
2021
Authors
Johnson, James W., author
McGilvray, Kirk C., advisor
Puttlitz, Christian, committee member
Ghosh, Soham, committee member
Easley, Jeremiah, committee member
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Abstract
Rotator cuff tendon tears are a prevalent issue worldwide; tears to these tendons can reduce arm mobility, cause pain, and decrease quality of life. Unfortunately, rotator cuff tendon tear repair surgeries experience unacceptable failures rates, with comorbidities such as age, chronic rotator cuff degeneration, or osteoporosis exacerbating these failures. The etiology of chronic degeneration is not fully understood, and there are no therapies or treatment capable of reversing or healing that condition. Furthermore, research is hindered due to the inability of current large animal translational models to faithfully recapitulate the wide range of changes noted in chronic degeneration. With that in mind, this work sought to improve the understanding of chronic rotator cuff degeneration through development of a clinically translatable large animal model and study of the injury and degeneration cascade. Specifically, this work has five components that will contribute to this body of knowledge. The first aim was to generate a model through transection of one half of the width of the tendon; unfortunately, this was found to result in differential changes on the two halves of the tendon that did not match the embodiment of changes seen clinically. The inadequacy and learnings from this model led to the generation of aims two and three. It has been hypothesized that chronic degeneration can result from untreated partial tears that are not diagnosed or treated with any conservative treatment. Aim 2 was focused on generating a chronic degeneration model through a clinically relevant bursal-side partial tear. Whereas Aim 3 was focused on creating a similar model without damaging the tendon insertion, providing the opportunity to screen therapies intended at halting or reversing the degeneration cascade. Aim 4 involved assessing tendons in an ovine model of osteoporosis for signs of degeneration as a means of determining the underlying cause for increased prevalence of rotator cuff repair failure in patients with osteoporosis. Aim 5 included characterization of the biomechanical, histological, and gene expression changes in cadaveric human rotator cuff tendons across a spectrum of ages as a means of better understanding the manifestation of chronic degeneration with the human rotator cuff. This aim was utilized as positive validation of the ovine models and as a means to generate design targets for repair scaffold mechanical properties. Aim 6 entailed generating a preliminary design of a scaffold capable of recapitulating the biomechanical properties of the healthy human supraspinatus tendons tested in Aim 5. Together, these proposed Aims provide new models of chronic rotator cuff degeneration, unique and novel data illuminating the multifactorial degeneration cascade in humans, and a prototype scaffold aimed at improving repair prognosis.
Description
Rights Access
Subject
chronic degeneration
osteoporosis
tendon
histopathology
biomechanics
rotator cuff