Multiscale Mechanical, Structural, and Compositional Response of Tendon to Static and Dynamic Loading During Healing

The extracellular matrix (ECM) is a major component of the biomechanical environment with which tendon cells (tenocytes) interact. Alterations to matrix structural and mechanical properties due to mechanical loading may promote normal tendon homeostasis or create pathological conditions. For example, fatigue loading of tendon elevates collagen fiber waviness (crimp), which correlates linearly with tissue laxity. The tendon ECM may also be altered following tendon injury. Aberrant tissue phenotypes caused by tendon ruptures are exemplified not only at transcript and protein levels, but also can extend to include disorganized collagen structure, inferior mechanical properties, and reduced in vivo limb function in animals. This dissertation explores the interface between dynamic loading and tendon healing across multiple length scales using living tendon explants. This work begins to define the implications of macroscale mechanical loading on collagen structure and tenocyte response in uninjured and healing tendon, and provides a foundation for the development of new strategies to improve tendon healing. Ultimately, this work helps our understanding of tendon’s multiscale response to loading, provides a framework for the micromechanical environment that tenocytes interact in response to dynamic loading and healing, and lays important groundwork for benchmarks for tendon tissue engineering. The multiscale response to mechanical loading, which is a hallmark of clinical rehabilitation protocols, is necessary to determine the ramifications of various macroscale loading protocols. Additionally, these results provide benchmarks for the environments in which tendon cells may experience following cell delivery therapies. Several exciting future avenues of research are possible that would highly impact basic science research of tendon function and lead to potentially translatable approaches that could improve tendon injury onset and healing response. In conclusion, this dissertation provides a strong foundation on which future experimental and computational studies can build to fully elucidate the multiscale mechanisms that govern strain transfer in tendon