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Development of Novel Energy-based Musculoskeletal Therapies


Back pain is the most common musculoskeletal condition, affecting 80% of Americans at some point in their lifetimes. Intervertebral disc (IVD) pathologies, such as annular tears and herniated discs, are the most common source of low back pain and account for more than 40% of cases. Current treatment options, including discectomy and intradiscal injections, involve invasive procedures and are limited to short-term symptom relief without repairing damaged IVDs. This dissertation explores the stimulatory effects and dose-response relationships of low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic fields (PEMF), with the goal of advancing the development of these energy-based therapies for the noninvasive treatment of low back pain. Towards this goal, this dissertation is broken into 4 studies. In the first study, we demonstrate the technical feasibility of targeted, noninvasive delivery of acoustic energy to rat-tail IVDs and evaluate gene expression changes in injured IVDs in response to LIPUS exposure. We found that LIPUS exposure regulates extracellular matrix and inflammatory gene expression in rats with increased proinflammatory gene expression. In the second study, we design, fabricate, characterize, and validate an in-vitro LIPUS exposimetry system for delivering uniform acoustic energy to cells while removing potentially confounding factors including beam reflections and sample heating. We demonstrate that far-field LIPUS exposure upregulates collagen synthesis in annulus fibrosus cells and is equivalent to growth factor treatment. In the third study, we present the use and validation of design of experiments (DOE) for LIPUS parameter exploration, response prediction, and optimization. We discovered that pulse repetition frequency is the most significant factor for modulating catabolic and proinflammatory gene expression while peak intensity is most significant for modulating anabolic gene expression, and that both factors interact with treatment duration to influence extracellular matrix gene expression in inflammatory annulus fibrosus cells. In the last study, we show that magnetic nano-bone substitutes (MNBS) synergize with PEMF to stimulate in-vitro osteogenesis. We found that the combination of PEMF and MNBS accelerates osteogenesis by stimulating early alkaline phosphatase activity and increasing mineralization over time in mesenchymal stem cells. Collectively, the work presented in this dissertation represents significant contributions to the development of two novel energy-based therapies for painful spine conditions. These findings will motivate the use of noninvasive, biologically active treatments for repairing damaged IVDs and alleviating low back pain.

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