Department of Clinical Sciences
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These digital collections include theses, dissertations, student publications, faculty publications, and datasets from the Department of Clinical Sciences.
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Browsing Department of Clinical Sciences by Author "Barrett, Myra F., committee member"
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Item Open Access Cartilage repair using trypsin enzymatic pretreatment combined with growth-factor functionalized self-assembling peptide hydrogel(Colorado State University. Libraries, 2019) Zanotto, Gustavo Miranda, author; Frisbie, David D., advisor; Grodzinsky, Alan, committee member; McIlwraith, C. Wayne, committee member; Barrett, Myra F., committee member; Puttlitz, Christian, committee memberTreatment of cartilage defects remains challenging in the orthopedic field. Several techniques are currently available to treat cartilage defects, with subchondral bone microfracture being the most commonly used marrow stimulation technique. However, despite satisfactory results in the short-term, clinical and functional outcomes of microfracture treated patients tend to decline over time. Improving microfracture technique using tissue engineering principles may be a more attractive way to treat cartilage defects compared to other more complex and expensive alternatives. Self-assembling peptide hydrogel has been extensively studied as a scaffold for cartilage repair. This hydrogel is biocompatible within the joint environment and has been shown to increase cartilage healing and improve clinical and functional outcomes in both rabbit and equine models of cartilage repair. Recently, a clinically applicable technique was described using trypsin enzymatic pretreatment of the surrounding cartilage combined with local delivery of heparin binding insulin growth factor-1 (HB-IGF-1). The results of this study demonstrated improved cartilage integration in vitro when this technique is utilized. Thus, in the present study we evaluated the combination of trypsin enzymatic pretreatment with a self-assembling peptide hydrogel functionalized with growth factors to improve cartilage repair. First, the effect of trypsin enzymatic pretreatment alone or combined with self-assembling peptide hydrogel functionalized with HB-IGF-1 and/or platelet-derived growth factor- BB (PDGF-BB) was tested using a rabbit model (48 rabbits). Subsequently, trypsin enzymatic pretreatment combined with self-assembling peptide hydrogel functionalized with HB-IGF-1 and PDGF-BB was used to augment microfracture augmentation in an equine model of cartilage defects (8 horses). In the small animal model, trypsin enzymatic pre-treatment resulted in an overall increase in defect filling, as well as improvements in subchondral bone reconstitution, surface regularity, cartilage firmness, reparative tissue color, cell morphology and chondrocyte clustering. The presence of PDGF-BB alone improved subchondral bone reconstitution and basal integration, while the combination of HB-IGF-1 and PDGF-BB resulted in an overall improvement in tissue and cell morphology. In the equine model, microfracture augmentation using trypsin enzymatic pretreatment combine with self-assembling peptide hydrogel functionalized with growth factors (HB-IGF-1 and PDGF-BB) resulted in better functional outcomes, better defect healing on second look arthroscopy at 12 months, as well as improved reparative tissue histology and increased biomechanical proprieties of the adjacent cartilage compared to defects treated with microfracture only. In conclusion, trypsin enzymatic pretreatment combined with self-assembling peptide hydrogel functionalized with growth factors (HB-IGF-1 and PDGF-BB) resulted in successful microfracture augmentation. These therapeutic approaches can result in a more cost effective way to improve cartilage healing in patients undergoing subchondral bone microfracture.Item Open Access Equine cervical pain and dysfunction(Colorado State University. Libraries, 2021) Story, Melinda R., author; Kawcak, Christopher E., advisor; Haussler, Kevin K., advisor; McIlwraith, C. Wayne, committee member; Nout-Lomas, Yvette S., committee member; Barrett, Myra F., committee member; Frisbie, David D., committee memberCervical pain and dysfunction in horses has become more recognized in recent years. However, a horse may present with a long list of different clinical syndromes and the examination findings can be confusing, resulting in difficulty effectively treating the horse. This frequently leads to frustration by the owner, as well as the veterinarian charged with helping the horse. This body of work aims to enlighten the reader of the dearth of understanding of cervical pain and dysfunction, to highlight how dangerous behavior may be related to cervical pain, and describe the course and development of future research. There is a paucity of peer-reviewed equine literature available describing cervical pain and dysfunction in the horse. The first chapter is designed to provide a synopsis of the current state of understanding of the disease processes, diagnostic capabilities, and possible treatment strategies available to manage cervical pain and dysfunction in horses. The second chapter describes a series of horses displaying unwanted behavior that became dangerous to the rider and often times to the horse itself. The included horses all had moderate to severe ganglionitis at multiple vertebral levels. Ganglionitis has been associated with neuropathic pain in other species, and is believed to be causing a state of neuropathic pain in this series of horses. This study highlights the need for deeper understanding of pain behavior in horses. Chapter 3 describes a prospective evaluation of cervical pain and dysfunction in 12 horses. Recombinant equine interleukin-1β (reIL-1β) has been used as an acute synovitis model within the appendicular skeleton and was utilized in this study to create transient synovitis at the cervical articulation of C5-C6. This study evaluated the clinical, biomechanical and ultrasonographic features in horses with a known source of neck pain. Acute synovitis of the articular process joint (APJ) induced clinical signs of myofascial pain and neck stiffness with variable degrees of forelimb lameness. Ultrasonographic evidence of the presence and severity of APJ effusion could be readily identified and tracked over time. Utilizing this model in the future could further add to our understanding of the clinical presentations in horses experiencing cervical pain and dysfunction. Through this collection of work, we have developed collaborations to investigate many unanswered questions that have been raised. We will look to define pathways related to neuropathic pain mechanisms in order to ultimately improve the quality of life, not only for our equine patients, but potentially of other veterinary species and even the human population experiencing chronic pain.Item Open Access Investigation of cationic contrast-enhanced computed tomography for the evaluation of equine articular cartilage(Colorado State University. Libraries, 2017) Nelson, Bradley B., author; Kawcak, Christopher E., advisor; Goodrich, Laurie R., advisor; McIlwraith, C. Wayne, committee member; Grinstaff, Mark W., committee member; Barrett, Myra F., committee memberOsteoarthritis and articular cartilage injury are substantial problems in horses causing joint pain, lameness and decreased athleticism resonant of the afflictions that occur in humans. This debilitating joint disease causes progressive articular cartilage degeneration and coupled with a poor capacity to heal necessitates that articular cartilage injury is detected early before irreparable damage ensues. The use of diagnostic imaging is critical to identify and characterize articular cartilage injury, though currently available methods are unable to identify these early degenerative changes. Cationic contrast-enhanced computed tomography (CECT) uses a cationic contrast media (CA4+) to detect the early molecular changes that occur in the extracellular matrix. Glycosaminoglycans (GAGs) within the extracellular matrix are important for the providing the compressive stiffness of articular cartilage and their degradation is an early event in the development of osteoarthritis. Cationic CECT imaging capitalizes on the electrostatic attraction between CA4+ and GAGs; exposing the proportional relationship between the amount of GAGs present within and the amount of CA4+ that diffuses into the tissue. The amount of CA4+ that resides in the tissue is then quantified through CECT imaging and estimates tissue integrity through nondestructive assessment. Despite the emergence of this promising technology to capture quantitative information on articular cartilage quality, cationic CECT has not been thoroughly investigated in equine tissues in vitro or in vivo, nor has it been investigated in in vivo in any large animal or human subjects. This compilation of studies was designed to critically examine the capacity of cationic CECT to provide quantitative information on articular cartilage quality across a continuum of disease states in horses while dually serving as a translational model to showcase its potential application in humans. The first experiments successfully characterized the diffusion properties of CA4+ into equine articular cartilage in vitro and in vivo, and also established the femoropatellar joint as the optimum joint for use in the subsequent in vivo experimental models. These initial studies also established preliminary evidence of the safety of CA4+ on articular tissues. The experimental in vivo equine impact model delivered a contusive force to articular cartilage that successfully instituted degeneration of the extracellular matrix components and decreased tissue stiffness. This subtle degradation was discernable from healthy articular cartilage using cationic CECT imaging (microCT). In vivo, the clinical cationic CECT attenuation demonstrated fair correlations with the biochemical, mechanical and histologic staining measures, though there was not sufficient delineation among groups to detect significant differences between disease states. Further investigations are warranted to determine how focal sites of injury can be identified from the resolution limited by current CT technology. The second in vivo experimental study generated reparative and degenerative articular cartilage to provide comparisons with healthy tissue. The cationic CECT method, using microCT and clinical scanners, demonstrated an ability to distinguish between these groups of varying articular cartilage quality. Though the results were promising, this study revealed the complexity of detecting subtle articular cartilage injury in a solitary imaging examination owing to the inherent biochemical and biomechanical variation that exists across articular surfaces. However, this study confirmed the successful monitoring of articular cartilage through longitudinal examinations. Overall, this collection of studies established that cationic CECT imaging in vitro and in vivo is capable of distinguishing articular cartilage across a spectrum of disease states exemplifying its utility in the comprehensive evaluation of equine articular cartilage. Further work of how this technique compares to other quantitative diagnostic imaging techniques and optimization strategies for routine use are required. Nonetheless, the results of this work reveal the excellent potential of cationic CECT imaging to be incorporated into research and clinical investigations in horses and highlight the feasible translation of this work into human tissues.