Doctoral Dissertation Defense – Ellen T. Bloom

BME PhD Candidate Ellen T. Bloom will be defending her dissertation:


A Tendon Model Using Mechanical Overload Causes Degenerative Multiscale Changes in Structure and Function



Tendon injuries are exceedingly common and afflict 16.4 million people yearly in the United States. As tendons are involved with all movement, these injuries can be debilitating for everyday life. Frequent among these injuries include tendon rupture and tendinopathy, both arising from excess mechanical loading to the tissue and leading to damage and degeneration. Tendon degeneration and mechanical damage are widely referred to as an overuse injury, with little distinction in the clinical or research communities between the magnitude of load (overload) or the number of cycles (overuse) as the injury mechanism. Because the clinical presentation between tendinopathy and tendon rupture are quite different, it is likely that different mechanisms and pathways lead to the end-stage degenerative state. Overuse and overload injuries develop over months in humans and early changes are not detectable, necessitating the use of animal models to evaluate the structural and mechanical changes throughout the degenerative process. However, animal models used to study tendon degeneration are mostly focused on overuse. As a result, it remains unknown how overload, in the absence of overuse, leads to tendon degeneration. Without a full understanding of the multiscale structure-function relationship and damage of tendon, treatments and interventions are doomed to remain ad hoc and not founded in rigorous physiology or etiology.

This dissertation addresses this gap in understanding the progression of degeneration by using novel multiscale structural and functional techniques in combination with an in vivo model of tendon overload. In one of the aims in this dissertation, we were able to assess tendon structural and functional degeneration in our in vivo model of tendon overload using activity monitoring, high-resolution MRI, histology, confocal microscopy, Serial Block Face Scanning Electron Microscopy, and multiscale mechanical testing. To ensure that we were accurately describing physiological damage, we first evaluated the effect of bathing solution osmolarity on ex vivo tendon mechanics. To measure collagen fibril geometry from a volumetric sample, we also developed a method using electron microscopy and machine learning to determine the 3D ultrastructure of collagen fibrils in dense tendon samples. From these three aims, we determined that bathing solutions which prevent tissue swelling result in more accurate tendon mechanics; successfully measured collagen fibril geometry in 3D tendon samples; and confirmed that our model of in vivo overload induced degenerative structural changes and impaired mechanical function of tendon.

The outcomes of this dissertation established an in vivo model to study overload-induced degeneration, separate from overuse, and will be used to study mechanisms and treatments for tendon overload injuries. The novel tools developed in this dissertation will be used in future research studying structure-mechanics studies of tendon and other highly aligned, collagenous soft tissue, as well as improving treatments and prevention strategies for tendon injuries.