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Browsing by Author "McGilvray, Kirk, advisor"

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    Development of a finite element model of supracondylar fractures stabilized with variable stiffness bone plates
    (Colorado State University. Libraries, 2019) Sutherland, Conor J., author; Puttlitz, Christian M., advisor; McGilvray, Kirk, advisor; Easley, Jeremiah, committee member; James, Susan, committee member
    Approximately 10% of orthopaedic fracture fixation cases lead to non-union, requiring surgical intervention. Inadequate fixation device stiffness, which causes unwanted fracture gap motion, is believed to be one of the largest factor in poor healing as it prevents ideal tissue proliferation in the callus. By altering the thickness of orthopaedic bone plates, it was theorized that the fracture gap micro-mechanics could be controlled and driven towards conditions that accommodate good healing. The first goal of the project was to create computational FEA models of an ovine femoral supracondylar fracture stabilized with a plate of varying thickness. The models were used to investigate the mechanical behavior of the plate and the callus under different physiological loading conditions. The second goal of this study was to validate the computational model with bench-top experiments using an ex-vivo ovine femoral fracture model. To achieve these goals, novel plates were designed and manufactured with different stiffnesses (100%, 85%, and 66% relative stiffness) to be used to treat a femoral supracondylar fracture model in ovine test subjects; both in-vivo and ex-vivo. The FE models were shown to accurately predict the stress/strain mechanics on both bone and plate surfaces. Micromechanics (strain and pressure) predictions in the fracture gap were reported and used to make tissue type proliferation predictions based on previously reported mechanics envelopes corresponding to bone remodeling. The results indicated that changing plate thickness successfully altered the construct stiffness and consequently, the predicted healing tissue type at the fracture site. The FE methods described could help improve patient specific fracture care and reduce non-union rates clinically. However, further in vivo testing is required to validate the clinical significance of the methods described in this thesis.
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    Development of novel mechanical diagnostic techniques for early prediction of bone fracture healing outcome
    (Colorado State University. Libraries, 2021) Wolynski, Jakob G., author; McGilvray, Kirk, advisor; Puttlitz, Christian, advisor; Heyliger, Paul, committee member; James, Susan, committee member; Wang, Zhijie, committee member
    To view the abstract, please see the full text of the document.
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    From the ovine to human rotator cuff; tenocyte as to MSC derived exosomes for tendon healing
    (Colorado State University. Libraries, 2024) von Stade, Devin P., author; Regan, Daniel, advisor; McGilvray, Kirk, advisor; Santangelo, Kelly, committee member; Hollinshead, Fiona, committee member
    Tendinopathies comprise one of the most widespread and economically significant diseases in developed nations. The societal value of rotator cuff tear surgical intervention alone has been estimated at greater than 3.4 billion US dollars despite frequent repair failures (30-79%). This drives great interest in adjunct therapies; however, research is complicated by a limited understanding of the underlying pathogenesis. Recent data suggests that the primary driver is cell-to-cell communication during the acute and chronic stages of rotator cuff tears. Most notably, the paracrine signaling of macrophages, which are preferentially recruited earlier and persist longer than other immune cells, may direct the structural function of injured tendons. Extracellular vesicles (EVs) are the primary contributors to the paracrine signaling responsible for many successful cell therapy studies. Investigations into mesenchymal stromal cell (MSC) derived EVs have served as a launching point toward this end, however, cell origin can dramatically change the effect of EVs on target cells. To explore the effects of exosomes as a function of cell source on tendon healing, we have developed in vitro models in human and ovine cell lines to test the effects of tissue native, tenocyte derived EVs as they compare to MSC derived EVs on key effectors of rotator cuff tears, tenocytes and macrophages. The goal of this work is to (a) describe the direct effect of EV education, as a function of cell source, MSC vs tenocyte, on macrophage gene regulation and cytokine production and tenocyte bioactivity; (b) to then assess the indirect effects of such EV educated macrophages on tenocyte bioactivity. (c) Additionally, the underlying pathogenesis of tendinopathy and the animal models of rotator cuff tears we use will be explored and further defined in the context of contemporary histologic and biomechanical methods.