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The Mechanobiology of Elbow Contracture: Pathogenesis and Prevention

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The Mechanobiology of Elbow Contracture: Pathogenesis and Prevention Washington University in St. Louis Washington University Open Scholarship Engineering and Applied Science Theses & Dissertations McKelvey School of Engineering Spring 5-15-2020 The Mechanobiology of Elbow Contracture: Pathogenesis and Prevention Chelsey Dunham Washington University in St. Louis Follow this and additional works at: https://openscholarship.wustl.edu/eng_etds Part of the Biomedical Engineering and Bioengineering Commons Recommended Citation Dunham, Chelsey, "The Mechanobiology of Elbow Contracture: Pathogenesis and Prevention" (2020). Engineering and Applied Science Theses & Dissertations. 541. https://openscholarship.wustl.edu/eng_etds/541 This Dissertation is brought to you for free and open access by the McKelvey School of Engineering at Washington University Open Scholarship. It has been accepted for inclusion in Engineering and Applied Science Theses & Dissertations by an authorized administrator of Washington University Open Scholarship. For more information, please contact [email protected]. WASHINGTON UNIVERSITY IN ST. LOUIS McKelvey School of Engineering Department of Biomedical Engineering Dissertation Examination Committee: Spencer Lake, Chair Aaron Chamberlain Gretchen Meyer Amit Pathak Lori Setton The Mechanobiology of Elbow Contracture: Pathogenesis and Prevention by Chelsey L. Dunham A dissertation presented to The Graduate School of Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2020 St. Louis, Missouri © 2020, Chelsey L. Dunham Table of Contents List of Figures ................................................................................................................................. v List of Tables ............................................................................................................................... xiv Acknowledgments......................................................................................................................... xv Abstract…. .................................................................................................................................. xvii Chapter 1: Introduction ................................................................................................................... 1 1.1 Motivation and specific aims ................................................................................................ 1 1.2 Summary of chapters ............................................................................................................. 3 1.3 References ............................................................................................................................. 6 Chapter 2: Background ................................................................................................................... 9 2.1 Post-traumatic elbow contracture .......................................................................................... 9 2.1.1 Elbow contracture in clinical settings .......................................................................................... 9 2.1.2 Joint contracture animal models ................................................................................................ 12 2.2 Stem cell injection therapies for fibrosis ............................................................................. 15 2.2.1 Fibrosis ....................................................................................................................................... 15 2.2.2 Stem cell injection therapies ...................................................................................................... 16 2.3 Mechanical memory ............................................................................................................ 17 2.4 References ........................................................................................................................... 20 Chapter 3: Persistent motion loss after free joint mobilization in a rat model of post-traumatic elbow contracture ........................................................................................................ 26 3.1 Introduction ......................................................................................................................... 26 3.2 Methods and materials ........................................................................................................ 27 3.3 Results ................................................................................................................................. 31 3.4 Discussion ........................................................................................................................... 35 3.5 References ........................................................................................................................... 40 Chapter 4: Pronation-supination motion is altered in a rat model of post-traumatic elbow contracture................................................................................................................... 42 4.1 Introduction ......................................................................................................................... 42 4.2 Methods and materials ........................................................................................................ 44 4.3 Results ................................................................................................................................. 51 ii 4.4 Discussion ........................................................................................................................... 53 4.5 References ........................................................................................................................... 58 Chapter 5: Temporal patterns of motion in flexion-extension and pronation-supination in a rat model of post-traumatic elbow contracture ................................................................ 61 5.1 Introduction ......................................................................................................................... 61 5.2 Methods and materials ........................................................................................................ 63 5.3 Results ................................................................................................................................. 70 5.4 Discussion ........................................................................................................................... 77 5.5 References ........................................................................................................................... 82 Chapter 6: The role of periarticular soft tissues in persistent motion loss in a rat model of post- traumatic elbow contracture ........................................................................................ 86 6.1 Introduction ......................................................................................................................... 86 6.2 Methods and materials ........................................................................................................ 87 6.3 Results ................................................................................................................................. 91 6.4 Discussion ........................................................................................................................... 94 6.5 References ........................................................................................................................... 98 Chapter 7: Muscle does not drive persistent post-traumatic elbow contracture in a rat model .. 100 7.1 Introduction ....................................................................................................................... 100 7.2 Methods and materials ...................................................................................................... 101 7.3 Results ............................................................................................................................... 108 7.4 Discussion ......................................................................................................................... 114 7.5 References ......................................................................................................................... 119 Chapter 8: Increased volume and collagen crosslinks drive soft tissue contribution to post- traumatic elbow contracture in an animal model ...................................................... 123 8.1 Introduction ....................................................................................................................... 123 8.2 Methods and materials ...................................................................................................... 125 8.3 Results ............................................................................................................................... 130 8.4 Discussion ......................................................................................................................... 137 8.5 References ......................................................................................................................... 141 Chapter 9: Soft primed adipose stem cells exhibit mechanical memory and decrease fibrosis and contracture in a rat elbow injury model .................................................................... 144 9.1 Introduction ......................................................................................................................
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