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Ryan C. Locke (1)
ProQuest Dissertations Publishing, 2020.
The burden of injury to tendon and the attachment between tendon and bone (i.e., the tendon-bone attachment) on quality of life, disability, health care, and the economy is significant. Unfortunately, current therapeutic interventions have high reinjury rates and do not restore the optimized multiscale structure and function of the healthy tendon or attachment. Investigations are needed to further develop and validate methods to prevent re-injury and improve tendon and attachment healing. The overall goal of this dissertation was to improve the preclinical translation of therapeutic interventions for tendon and attachment injury. The body of work in this dissertation helps to translate therapeutic interventions for tendon and attachment injury by establishing (1) an improved animal model of attachment injury, (2) success criteria for preclinical translation of hydrogels for tendon repair, (3) the safety and efficacy of a clinically available therapy, and (4) biomarkers of tendon injury. The first aim of this research was to develop and validate a rat model of localized and partial-thickness attachment injury. The first part of this aim established the multiscale biomechanical properties of the attachment with and without localized defects ex vivo. Biomechanical tests validated that strain concentrations localize at the defect site, suggesting that defects may propagate in vivo. The final part of this aim established the cellular, structural, and biomechanical healing capacity of the attachment in vivo. Collectively, this aim established that the attachment has limited healing capacity and validated this animal model for continued preclinical translation of therapeutic interventions for improving the healing capacity of the attachment.
Dragonfly was used to measure bone morphometric properties for the defect area, greater tubercle, and proximal epiphysis. It was also used for digital painting and to isolate and analyze total, trabecular, and cortical bone ROIs.
(1) Department of Biomedical Engineering, University of Delaware.
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