Muscle Loading Treatments for Achilles Tendinopathy
| dc.contributor.author | Easley, Dylan Cole | en |
| dc.contributor.committeechair | Wang, Vincent M. | en |
| dc.contributor.committeemember | Grange, Robert W. | en |
| dc.contributor.committeemember | Brolinson, Per Gunnar | en |
| dc.contributor.committeemember | Dahlgren, Linda A. | en |
| dc.contributor.committeemember | Li, Liwu | en |
| dc.contributor.department | Graduate School | en |
| dc.date.accessioned | 2025-02-08T09:00:10Z | en |
| dc.date.available | 2025-02-08T09:00:10Z | en |
| dc.date.issued | 2025-02-07 | en |
| dc.description.abstract | Tendinopathies are common, painful, and debilitating injuries that can be challenging to treat. Current treatment methods are limited to surgery, nonsteroidal anti-inflammatory drugs, dry needling, and injectable therapeutics, platelet rich plasma and corticosteroids. Unfortunately, these existing treatments display poor long-term outcomes and have an increased risk of reinjury. Additionally, the healing mechanism for injured tendons forms scar tissue which is characterized by disrupted extracellular matrix rather than complete injury resolution. These structural changes impact the mechanical properties of tendon, reducing their capacity to transfer and store energy, making them inferior to uninjured tendons. The reduced mechanical properties increase the risk of rupture, exacerbating this debilitating disease and decreasing quality of life. Physical therapy (eccentric loading) decreases the symptoms of tendinopathy and restores Achilles tendon functionality. However, the mechanism by which these mechanical stimulations induce healing is poorly understood. There is a clinically relevant motivation to better understand the healing cascade in response to eccentric exercises. We aim to identify and characterize the effects of eccentric rehabilitative muscle loading on the Achilles tendon and gastrocnemius muscle complex using our preclinical TGF-ß1-induced murine model of Achilles tendinopathy. To accomplish our objective, we tested three muscle loading magnitudes (50%, 75%, and 100% body weight), over three treatment durations (1, 2, and 4 weeks) to determine their effects on tendon healing. Age-matched injured/untreated and naïve groups accompanied each loading magnitude and duration period. The functional biomechanical properties, morphological adaptations, transcriptomic response, and muscle strength of the Achilles tendon were assessed. Injured/untreated tendons had a significantly increased cross-sectional area compared to naïve and all loading groups at 2 and 4 weeks. Maximum stress and elastic modulus of injured/untreated tendons were significantly lower compared to naïve and all loading groups after 4 weeks. Gastrocnemius muscle strength was maintained over time as loading magnitude increased. Force output was lower after 2 weeks at 100% body weight loading compared to the naïve group, then recovered to naïve levels after 4 weeks. Histological findings included increased cross-sectional area, matrix disorganization, and increased cellular density of injured/untreated tendons. The transcriptomic evaluation revealed several patterns of expression among exercised groups. Biological processes associated with exercised groups revealed genes responsible for inflammation, extracellular matrix organization, and cell to cell signaling. Overall, eccentric muscle loading improved tendon geometry and material properties compared to naïve levels and improved muscle strength over time. Morphological evaluation also showed improvements in cross-sectional area, and collagen orientation, and cell appearance after 2 and 4 weeks of eccentric loading. Similarly, the transcriptomic changes showed an effect from exercise and upregulation of genes essential for extracellular matrix organization, inflammatory regulation, and cell to cell signaling. | en |
| dc.description.abstractgeneral | Tendons are connective tissues that join muscle to bone to facilitate movement. Tendons are prone to injury because of their consistent use for daily activities. The Achilles tendon is particularly at risk for injury since it is responsible for walking, running, and jumping, making it susceptible to overuse. Current treatment methods such as surgery and pain relief medication can provide immediate symptomatic relief, but have limited long-term success. Physical therapy provides relief of symptoms of chronic Achilles tendinopathy and improves the tendon healing response. Eccentric-based exercises (lengthening of the muscle while it contracts) are known as 'heel drops' and have been the most successful physical therapy technique to improve Achilles tendon healing. However, the way these rehabilitative exercises facilitate healing is poorly understood. It is difficult to determine the exact methods of healing because the required frequency and amount of exercise varies between patients, and recovery times can take weeks or months. In this research, we aim to better characterize how different 'heel drop' routines improve tendon healing, providing a foundation for determining the intensity and duration of rehabilitative exercises that can be applied for better clinical outcomes. To examine the effects of different eccentric-based loading profiles, we used a previously developed mouse model of chronic Achilles tendinopathy and customizable muscle stimulation device to simulate human physical therapy exercises at different intensity levels: full body weight (100%), assisted body weight (75%), and half body weight (50%). Prior to beginning treatments, we induced a tendon injury that mimics human injury and measured muscle strength before any exercise was performed. Mice were then introduced to muscle loading treatments that mimic clinical exercise routines: 3 sets of 10 heel drops, performed twice a week for 1-, 2- or 4-weeks. After the final day of exercise, muscle strength was measured again to see how the heel drop exercises impacted the muscle tissue. Tendons were collected and the mechanical properties, histologic changes, and transcriptomic adaptations were evaluated. Eccentric-based exercises improved the mechanical properties injured tendons and improved the architecture compared to injured/untreated controls. Injured tendons without treatment had inferior tendon mechanical properties and inferior structural changes. We also saw improved tissue changes and upregulation of genes responsible for tendon healing after exercise compared to naïve or injured/untreated mice. Our research demonstrates that performing consistent eccentric-based exercises for 2 or more weeks positively impacts tendon healing. | en |
| dc.description.degree | Doctor of Philosophy | en |
| dc.format.medium | ETD | en |
| dc.identifier.other | vt_gsexam:41262 | en |
| dc.identifier.uri | https://hdl.handle.net/10919/124536 | en |
| dc.language.iso | en | en |
| dc.publisher | Virginia Tech | en |
| dc.rights | In Copyright | en |
| dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | en |
| dc.subject | Achilles | en |
| dc.subject | Tendinopathy | en |
| dc.subject | Tendon Healing | en |
| dc.subject | Eccentric Muscle Loading | en |
| dc.subject | Biomechanics | en |
| dc.subject | Transcriptomics | en |
| dc.title | Muscle Loading Treatments for Achilles Tendinopathy | en |
| dc.type | Dissertation | en |
| thesis.degree.discipline | Translational Biology, Medicine and Health | en |
| thesis.degree.grantor | Virginia Polytechnic Institute and State University | en |
| thesis.degree.level | doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |
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