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No description available.

Voice disorders affect up to 9% of the population, and can be caused by vocal fold scarring. They can reduce the ability of a person to participate in the workplace and can also cause depression in individuals. Vocal fold scarring changes the organization and composition of the lamina propria, and affects the biomechanical properties of the tissue. These changes cause an inability of the lamina propria to produce a normal mucosal wave during speech, resulting in hoarseness or complete voice loss. Currently there is a clinical need for treatment options for vocal fold scarring. This work focuses on developing a novel, elastomeric electrospun biomaterial to be used as a model system to evaluate the response of immortalized human vocal fold fibroblast cells (HVFF) to scaffold architecture and to the presence of an elastin polypeptide. The scaffold was developed by electrospinning Tecoflex™. Electrospun scaffolds were successfully made with aligned and unaligned fibers, and they were characterized using scanning electron microscopy (SEM) and uniaxial tensile testing. The aligned scaffolds had initial elastic moduli of ~14 MPa and ~0.3 MPa in the preferred and cross-preferred direction respectively. The unaligned scaffolds had initial elastic moduli of ~5 MPa and ~0.6 MPa in the preferred and cross-preferred direction respectively. An elastin-like polypeptide (ELP) developed in the Woodhouse lab, ELP4, was successfully adsorbed onto the scaffolds to investigate the effect of ELP’s on the HVFF cells. HVFF cells were seeded onto the scaffolds and their viability, proliferation, morphology, and gene expression were characterized. Over the culture period the cells remained viable, and showed signs of proliferation. The scaffold topography had a significant impact on the orientation of the cells, with very aligned cultures on the aligned scaffold, and randomly oriented cells on the unaligned scaffold. The scaffold alignment and the ELP4 coating impacted the extracellular matrix gene expression. The ELP4 coating, and the aligned scaffolds promoted elastin synthesis when tested on day 7, and may also reduce collagen-3 expression on day 3. These results signify that aligned electrospun scaffolds, as well as an ELP4 coating, may be promising to use in future biodegradable vocal fold constructs. / Thesis (Master, Chemical Engineering) -- Queen's University, 2013-09-26 09:49:22.891

Osteological studies have identified scarring on the bone surface of the human pelvic bone as evidence of childbirth, termed parturition scarring. It remains unknown whether a single or multiple births cause parturition scarring. Such scarring has also been found on male pelvic bones. This study examines parturition scarring within the broader morphometric and musculoskeletal context of the pelves of both sexes. This project investigates the influence of body size (stature and body mass) and pelvic size (individual pelvic measurements and pelvic canal size) and shape (pelvic canal shape) on the presence of parturition scarring on the pelvic bones of females and males. Two skeletal collections of known-age and sex were chosen for this project on the basis of access to parity (childbirth) records: the Maxwell Museum Documented Skeletal Collection and the Christ Church, Spitalfields collection. The dimensions of articulated and disarticulated pelves, femoral measurements and scores for six types of parturition scarring were recorded for all individuals (n=292). Skeletal proxies for body mass and stature were calculated for all individuals. Univariate, bivariate and multivariate statistical analyses were used to identify significant differences in parturition scarring between sexes, correlation between body size variables, parity status, pelvic canal size and pelvic canal shape (as represented by principal components analysis) and parturition scarring. Parity status and pelvic canal shape do not associate with parturition scarring. Pubic tubercle variables associated variously with femoral head diameter and pelvic canal size in females or males only. Dorsal pitting correlates weakly with four pelvic dimensions in females. The results of this study suggest that the term parturition scarring should be revised to reflect its non-connection with parity status and that future investigations should examine musculoskeletal interactions based on body and pelvic size variation that affect the presence of such scarring in males. / Graduate / 0327 / 0287 / decrausa@uvic.ca

Osteological studies have identified scarring on the bone surface of the human pelvic bone as evidence of childbirth, termed parturition scarring. It remains unknown whether a single or multiple births cause parturition scarring. Such scarring has also been found on male pelvic bones. This study examines parturition scarring within the broader morphometric and musculoskeletal context of the pelves of both sexes. This project investigates the influence of body size (stature and body mass) and pelvic size (individual pelvic measurements and pelvic canal size) and shape (pelvic canal shape) on the presence of parturition scarring on the pelvic bones of females and males. Two skeletal collections of known-age and sex were chosen for this project on the basis of access to parity (childbirth) records: the Maxwell Museum Documented Skeletal Collection and the Christ Church, Spitalfields collection. The dimensions of articulated and disarticulated pelves, femoral measurements and scores for six types of parturition scarring were recorded for all individuals (n=292). Skeletal proxies for body mass and stature were calculated for all individuals. Univariate, bivariate and multivariate statistical analyses were used to identify significant differences in parturition scarring between sexes, correlation between body size variables, parity status, pelvic canal size and pelvic canal shape (as represented by principal components analysis) and parturition scarring. Parity status and pelvic canal shape do not associate with parturition scarring. Pubic tubercle variables associated variously with femoral head diameter and pelvic canal size in females or males only. Dorsal pitting correlates weakly with four pelvic dimensions in females. The results of this study suggest that the term ‘parturition scarring’ should be revised to reflect its non-connection with parity status and that future investigations should examine musculoskeletal interactions based on body and pelvic size variation that affect the presence of such scarring in males. / Graduate / 0327 / 0287 / decrausa@uvic.ca

Blast-induced neurotrauma (BINT) is a major societal concern due to the complex expression of neuropathological disorders after exposure to blast. Disruptions in neuronal function, proximal in time to the blast exposure, may eventually contribute to the late emergence of the clinical deficits. Besides complications with differential clinical diagnosis, the biomolecular mechanism underlying BINT that gives rise to cognitive deficits is poorly understood. Some pre-clinical studies have demonstrated cognitive deficits at an acute stage following blast overpressure (BOP) exposure. However, the behavioral deficit type (e.g., short term memory) and the mechanism underlying injury prognosis that onsets the cognitive deficits remains to be further investigated. An established rodent model of blast neurotrauma was used in order to study impaired behavioral and neuropathological outcomes following blast. Anesthetized rats were exposed to a calibrated BOP using a blast simulator while control animals were not exposed to BOP. Behavioral changes in short term memory and anxiety were assessed with standard behavioral techniques (novel objected recognition paradigm and light and dark box test) at acute and chronic stages (range: 3 hours -- 3 months). In addition, brains were assayed for neurochemical changes using proton magnetic resonance spectroscopy (MRS) and neuropathology with immunohistochemistry in cognitive regions of brain (hippocampus, amygdala, frontal cortex and nucleus accumbens) Early metabolic changes and oxidative stress were observed along with a compromise in energy metabolism associated with sub-acute (7 days following BOP exposure) active neurodegeneration and glial scarring. Data suggested GABA shunting pathway was activated and phospholipase A2 regulated arachadonic acid pathway may be involved in cellular death cascades. In addition, increased myo-inositol levels in medial pre-frontal cortex (PFC) further supported the glial scarring and were associated with impaired working memory at a sub-acute stage (7 days) following BOP exposure. Chronic working memory issues and anxiety associated behavior could be related to chronic activation of microglia in hippocampus and astrocytes in amygdala respectively. Furthermore, these results from MRS could be directly translated into clinical studies to provide a valuable insight into diagnosis of BINT, and it is speculated that gliosis associated markers (myo-inositol) may be a potential biomarker for blast-induced memory impairment. / Ph. D.

Drug development research on wound repair is challenging and inefficient due to the complex nature of wound healing and scarring processes and the limitations of available in vitro or in vivo models used for preclinical drug testing. Many patients who undergo elective back surgery develop post-surgical complications resulting from excess peridural scarring in and around the site of operation. We tested the effects of two anti-inflammatory compounds, quercetin and L-2-oxothiazolidine-4-carboxylate (OTC), in ameliorating peridural scar formation following spinal laminectomy surgery in laboratory rats. Western blot and immunocytochemical analyses indicated that the peridural scar tissue contained MyoD-positive myoblast cells and expressed prolyl-4-hydroxylase (P4H), a fibroblast marker. Treatment with 1 mM OTC reduced activation of ERK1/2 and p38 mitogen-activated protein kinases (MAPK) at 21 days post-surgery suggesting potential anti-scarring mechanism. However, large animal to animal variation in the expression levels of collagen biosynthesis markers made it difficult to demonstrate any efficacy of quercetin or OTC in reducing peridural scar formation. The shortcomings of this live animal approach led us to develop a novel three-dimensional (3-D) <i>in vitro</i> wound repair model for evaluating quercetin and OTC effects. High-density micromass co-cultures seeded at a 1:3 ratio of FR 3T3 fibroblast cells and L8 myoblast cells formed 3-D microtissues <i>in vitro</i> that expressed MyoD, P4H, and á-smooth muscle actin. The micromass tissue layer remained adherent to the culture plate when inflicted with a single laceration injury, which allowed monitoring of cell migration into the wound site. Wounded cultures were treated with quercetin, OTC and other agents (TGF- â1, mitomycin, p38 inhibitor SB202190, ERK inhibitor PD184352) to determine their effects on collagen accumulation, wound closure rates, MAPK activation, and gene transcript expression. Both OTC and quercetin treatments reduced collagen biosynthesis in dose-dependent manner. In addition, 1.5 mM OTC accelerated wound closure and significantly reduced p38 MAPK activation without affecting ERK1/2. In contrast, 40 µM quercetin delayed wound closure in micromass co-cultures and reduced ERK1/2 activation. Our in vitro findings suggest that OTC might have potential as an anti-scarring agent. Importantly, our novel micromass co-culture system shows promise as an improved 3-D scaffold-free in vitro model for use in preclinical drug development research.

Drug development research on wound repair is challenging and inefficient due to the complex nature of wound healing and scarring processes and the limitations of available in vitro or in vivo models used for preclinical drug testing. Many patients who undergo elective back surgery develop post-surgical complications resulting from excess peridural scarring in and around the site of operation. We tested the effects of two anti-inflammatory compounds, quercetin and L-2-oxothiazolidine-4-carboxylate (OTC), in ameliorating peridural scar formation following spinal laminectomy surgery in laboratory rats. Western blot and immunocytochemical analyses indicated that the peridural scar tissue contained MyoD-positive myoblast cells and expressed prolyl-4-hydroxylase (P4H), a fibroblast marker. Treatment with 1 mM OTC reduced activation of ERK1/2 and p38 mitogen-activated protein kinases (MAPK) at 21 days post-surgery suggesting potential anti-scarring mechanism. However, large animal to animal variation in the expression levels of collagen biosynthesis markers made it difficult to demonstrate any efficacy of quercetin or OTC in reducing peridural scar formation. The shortcomings of this live animal approach led us to develop a novel three-dimensional (3-D) <i>in vitro</i> wound repair model for evaluating quercetin and OTC effects. High-density micromass co-cultures seeded at a 1:3 ratio of FR 3T3 fibroblast cells and L8 myoblast cells formed 3-D microtissues <i>in vitro</i> that expressed MyoD, P4H, and á-smooth muscle actin. The micromass tissue layer remained adherent to the culture plate when inflicted with a single laceration injury, which allowed monitoring of cell migration into the wound site. Wounded cultures were treated with quercetin, OTC and other agents (TGF- â1, mitomycin, p38 inhibitor SB202190, ERK inhibitor PD184352) to determine their effects on collagen accumulation, wound closure rates, MAPK activation, and gene transcript expression. Both OTC and quercetin treatments reduced collagen biosynthesis in dose-dependent manner. In addition, 1.5 mM OTC accelerated wound closure and significantly reduced p38 MAPK activation without affecting ERK1/2. In contrast, 40 µM quercetin delayed wound closure in micromass co-cultures and reduced ERK1/2 activation. Our in vitro findings suggest that OTC might have potential as an anti-scarring agent. Importantly, our novel micromass co-culture system shows promise as an improved 3-D scaffold-free in vitro model for use in preclinical drug development research.