Master of Science in Biomedical Engineering
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Mao, Jiahui
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Abstract
Rotator cuff tear (RCT) is one of the most common causes of shoulder pain and disability, and surgical repairs of RCT have a high risk of re-tear, and they are unable to address the disrupted supraspinatus muscle microenvironment, which then leads to muscle degeneration phenotypes such as muscle atrophy, fatty infiltration, fibrosis and inflammation. Our team hypothesized that delivering anti-inflammatory drugs in a controlled manner into the injured supraspinatus muscle would mitigate muscle inflammatory response, shift cellular phenotypes toward a pro-regeneration state, and promote muscle regeneration. In this study, we aimed to evaluate two anti-inflammatory drugs that have the potential to shift the spectrum of macrophage polarization from inflammatory M1-like macrophages to anti-inflammatory M2-macrophages. We used a heparin-containing poly(ethylene glycol) hydrogel system for the in vivo controlled delivery of those therapeutic drugs. In this study, muscle cross- sectional area, embryonic myosin heavy chains and centrally located nuclei were evaluated as markers of muscle regeneration. We found the sustained release of anti-inflammatory drug TSG-6 from fully sulfated heparin hydrogel fragments significantly promoted muscle regeneration compared to other groups. We also identified spatiotemporal identities of muscle regeneration that muscle regeneration was significantly more pronounced at muscle regions that were closer to the tendon, and the regeneration markers peaked at their unique timepoints. Additionally, a proof-of-concept study was conducted for the drug IL-10, and the effect of this drug on muscle regeneration will be evaluated in the future.
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2024-07-22
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