Global ETD Search

171	Effects of Neuromuscular Training in Anterior Cruciate Ligament-Reconstructed Subjects Wordeman, Samuel Clayton January 2014 (has links) No description available. Biomedical Engineering Biomechanics Engineering Health Sciences Mechanics Physical Education
172	Tibia Morphology & Bone Marrow Adipose Tissue Phenotype is Controlled by Sex Steroids in C57BL/6 Mice Sherman, Shermel B. January 2016 (has links) No description available. Endocrinology Biomedical Research
173	Comparative pilot study of 3D Manufactured and Conventional Manufactured Custom Made Foot Orthotics when looking at Plantar Pressure Distribution and Comfort in adults Mågård-Hansen, Alexander, Sejersen, Camilla Louise January 2024 (has links) Background 3D manufacturing is a newer technology that shows potential and has gained interest in the world of medical devices. It has been used to produce custom made foot orthotics (CFO)s, but little evidence on the biomechanical effects is available. The literature suggests that the 3D manufactured CFOs (3DMCFO) have comparable outcomes as conventional manufactured CFOs (CMCFO). Purpose The purpose of this pilot study was to investigate biomechanics and comfort in the 3D manufacturing method, because of the lack of biomechanical evidence in literature, and because comfortable orthotics are a prerequisite for an optimal foot orthosis. Methods This pilot project uses a randomized crossover study design to test if there is a difference in plantar pressure distribution and comfort between 3DMCFOs and CMCFOs on two participants (n=2). To investigate the plantar pressure distribution the F-scan® in-shoe sensors was used to measure peak plantar pressures. To evaluate comfort the Orthosis Comfort Score (OCS) was used. Result For both participants similar results of mean peak pressures could be seen in some areas in the two CFOs, where in other areas contradictory results were seen. The comfort in the two CFOs was similar. Conclusion Similarities was seen in plantar pressure distribution and comfort in the two CFOs in both participants. However, the validity and reliability are low because of the low number of participants. / Baggrund 3D print er en nyere produktionsmetode som viser potentiale og har vækket interesse inden for medicinske hjælpemidler. 3D printning er blevet brugt til at producere specialfremstillede fod ortoser (SFO), men der er lav evidens for dens biomekaniske effekt. Litteraturen viser at 3D printede SFOer har sammenlignelige resultater som konventionel produceret SFOer. Formål Formålet med dette projekt var at undersøge biomekanik og komfort for 3D- produktionsmetoden. Dette blev undersøgt fordi der er lidt evidens inden for området, og fordi komfort er en forudsætning for en optimal fod ortose. Metode Dette pilotstudie bruger et randomiseret kontrolleret studie design for at teste om der er en forskel imellem 3D produktionsmetoden og den konventionelle produktionsmetode når der kigges på trykfordeling og komfort i to deltagere (n=2). For at undersøge trykfordeling under foden bruges F- scan® indlæg-sensor, for komfort bruges The Orthosis Comfort Score. Resultat For begge deltagere var der overensstemmelser i de gennemsnitlige høje tryk og i komfort for begge SFOer, hvor der i nogen områder var uoverensstemmelser. Konklusion For de to SFOer, overensstemmelser kunne ses i trykfordelingen under foden og i komfort. Validiteten og pålideligheden for dette projekt er dog ikke højt på grund af det lave deltagerantal. biomechanics CAD/CAM peak pressure randomized crossover study EVA TPU manufacturing methods foot orthotics insoles biomekanik CAD/CAM plantar tryk randomiseret kontrolleret studie design EVA TPU produktions metoder fod ortoser indlæg Orthopaedics Ortopedi
174	Identification and characterisation of epigenetic mechanisms in osteoblast differentiation of human mesenchymal stem cells Kramm, Anneke January 2014 (has links) A major therapeutic challenge in musculoskeletal regenerative medicine is how to effectively replenish bone tissue lost due to pathological conditions such as fracture, osteoporosis, or rheumatoid arthritis. Mesenchymal stem cells are currently investigated for applications in bone-tissue engineering and human bone marrow-derived mesenchymal stem cells (hMSCs) could be a promising source for generation of tissue-engineered bone. However, the therapeutic potential of MSCs has not been fully exploited due to a lack of knowledge regarding the identity, nature, and differentiation of hMSCs. Epigenetic mechanisms regulating the chromatin structure as well as specific gene transcription are crucial in determination of stem cell differentiation. With the aim to systematically identify epigenetic factors that modulate MSC differentiation, the work in this thesis encompasses an approach to identify epigenetic mechanisms underlying, initiating, and promoting osteoblast differentiation, and the investigation of individual epigenetic modulators. Various osteogenic inducers were validated for differentiation of MSCs and an assay allowing assessment of differentiation outcome was developed. This assay was subsequently employed in knockdown experiments with lentiviral short hairpin RNAs and inhibitor screens with small molecules targeting putative druggable epigenetic modulator classes. This approach identified around 100 epigenetic modulator candidates involved in osteoblast differentiation, of these candidates approximately 2/3 downregulated and 1/3 upregulated alkaline phosphatase (ALP) activity. Serving as a proof-of-concept, orthogonal validation experiments employing locked nucleic acid (LNA) knockdown were performed to validate a subset of candidates. Two identified target genes were selected for further investigation. Bromodomain-containing protein 4 (BRD4) was identified as one component of epigenetic regulation; its inhibition led to a decrease in ALP expression, downregulation of key osteoblast transcription factors Runx2 and Osterix, as well as impaired bone matrix formation. Knockdown of lysine (K)-specific demethylase 1A (KDM1A/LSD1) upregulated ALP activity and treatment with a small molecule inhibitor targeting KDM1A led to an increase in ALP, RUNX2, and bone sialoprotein expression. Intriguingly, in a transgenic mouse model overexpressing Kdm1a a decrease in bone volume and bone mineral density was observed, thus supporting the hypothesis that KDM1A is a central regulator of osteoblast differentiation. 616.02
175	Extracellular Matrix Based Materials for Tissue Engineering Aulin, Cecilia January 2010 (has links) The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies. Extracellular matrix collagen synthesis bioreactor cell culture bone morphogenetic protein-2 noggin hyaluronan cartilage Medical technology Medicinsk teknik Molecular biology Molekylärbiologi Orthopaedics Ortopedi Transplantation surgery Transplantationskirurgi Biomaterials Biomaterial Morphology, cell biology, pathology Morfologi, cellbiologi, patologi Cell and molecular biology Cell- och molekylärbiologi Polymer chemistry Polymerkemi Materials chemistry Materialkemi
176	Optimizing Engineered Tendon Development via Structural and Chemical Signaling Cues Thomas Lee Jenkins II (16679865) 02 August 2023 (has links) <p>The rotator cuff is a group of four muscles and tendons in the shoulder that function to lift and rotate the arm. Rotator cuff tendon tears are increasingly common: more than 545,000 rotator cuff surgeries occur annually in the US. However, treatment is often complicated by disorganized collagen matrix formed via fibrosis and results in high re-tear rates. Tendon tissue engineering seeks to solve the problem using biomaterials to promote neo-tendon formation to augment repair or regenerate tendon. However, while current biomaterials provide the opportunity to improve tendon healing, they frequently still exhibit fibrosis in preclinical studies. Therefore, a critical need exists to understand the mechanisms of aligned collagen formation when designing biomaterials for tendon tissue engineering. Matrix architecture and transient receptor potential cation channel subfamily V member 4 (TRPV4) regulate aligned collagen formation during tenogenesis in vitro, but the mechanism remains to be determined. Recently, TRPV4 stimulation was found to induce nuclear localization and activation of transcriptional co-activators Yes-associated protein (YAP). YAP expression is upregulated during tendon development, a process characterized by aligned collagen formation, and in response to physiological mechanical stimulation, suggesting it could play an important role in tendon. The objective of this work is to improve tissue engineering strategies and progress toward making a device that regenerate tendon after injury. Aim 1 incorporates tendon-derived matrix into synthetic polymer scaffolds to add biological signaling cues to induce tenogenesis. Aim 2 uses a 2D photolithography system (microphotopatterning) to optimize architectural and structural cues to promote stem cell differentiation toward tenogenic, chondrogenic, and osteogenic lineages. Aim 3 investigates dynamic tensile loading protocols to promote collagen matrix synthesis and improve engineered tendon mechanical function. Aim 4 investigates the role of TRPV4 and YAP in collagen alignment during engineered tendon development.</p> Orthopaedics Biomaterials Mechanobiology Tissue engineering Biomechanics tendon tissue engineering biomaterials metlblowing electrospinning adipose stromal/stem cells (ASCs) Collagen alignment Extracellular matrix (ECM) synthesis carbodiimide cross-linking UV cross-linking viscoelastic properties calculated Tensile loading cyclical loading Transient receptor potential vanilloid 4 yes-associated protein
177	<b>CHARACTERIZATION OF SERPINA1 IN ADULT SPINAL HOMEOSTASIS TO INFORM TREATMENT STRATEGIES</b> Neharika Bhadouria (17266174) 07 December 2023 (has links) <p dir="ltr">People suffering from COPD are also known to suffer from other musculoskeletal issues like fracture risk, back pain, etc. Intervertebral disc degeneration (IVD) is a prominent cause of back pain and inflammation, influenced by factors such as aging, sudden loading, and genetics. <i>SERPINA1</i>, a common genetic variant in individuals with chronic obstructive pulmonary disease (COPD), encodes the alpha-antitrypsin protein (AAT). AAT deficiency is also associated with IVD degeneration, bone loss, and gait impairment. Currently, AAT-deficient individuals receive costly and short-lived weekly AAT injections, with no established guidelines for managing IVD degeneration and osteoporosis. Our primary research objective was to examine the effects of <i>serpinA1a/c</i> using a mouse model with global knockout (KO) of <i>serpinA1a/c</i>, generated through CRISPR technology, on intervertebral discs (IVD) and bone. We found that global deletion of <i>serpinA1a/c</i> was found to cause IVD elastin degradation, leading to a loss of mechanical properties. Moreover, <i>serpinA1</i> was associated with increased bone-resorbing cells (osteoclasts) and a reduction in bone-forming cells (osteoblasts). Notably, sexual dimorphism was observed, with female IVDs exhibiting less degeneration than male counterparts, and <i>serpinA1a/c</i> KO mice were protected from mechanically-induced tail compression. Even in human IVDs, males expressed more AAT-1 compared to female IVDs. There are no FDA-approved drugs currently existing for IVD degeneration. Since IVD degeneration frequently occurs in individuals with osteoporosis, it shows a probable cross-talk happening between IVD and bone. In our study, we found the association of <i>serpinA1 </i>with estrogen receptor alpha and osteoclasts. Hence, we investigated the potential of raloxifene, an FDA-approved selective estrogen receptor modulator (SERM) typically prescribed to post-menopausal women for osteoporosis treatment, in averting IVD degeneration and improving mechanical characteristics in IVD. Our findings suggest that raloxifene injection may retard IVD degeneration induced by AAT deficiency, particularly in male mice. Furthermore, the latter study touched upon a conditional <i>serpinA1a</i> mouse model crossed with aggrecan-cre, specifically targeting <i>serpinA1a</i>-expressing cells in the IVD while sparing bone. Conditional <i>serpinA1a</i> deletion induced mild IVD degeneration without affecting bone loss. In summary, this study serves as a foundation for testing potential treatments for AAT patients with IVD degeneration and osteoporosis. It also provides compelling evidence for considering raloxifene as a treatment option for IVD degeneration in AAT-deficient patients experiencing IVD-related pain.</p> Genetically modified animals Animal structure and function Respiratory diseases Orthopaedics Pain Surgery Biomedical imaging Biomechanics SERPINA1 gene Raloxifene/pharmacokinetic Intervertebraldisc bone intervertebral disc injury Human intervertebral disc discogenic pain genetically modified animals Sex dimorphism aging behavioral assays Magnetic resonance Imaging Chronic obstructive pulmonary disease Spine biomechanics AAT-1 alpha-antitrypsin emphysema crosstalk treatment EVISTA tail disc lumbar disc tail compression FTIR QPCR Gene expression SerpinA1 isoforms lung conditional KO mice Global KO mice
178	Genetics of ankylosing spondylitis Karaderi, Tugce January 2012 (has links) Ankylosing spondylitis (AS) is a common inflammatory arthritis of the spine and other affected joints, which is highly heritable, being strongly influenced by the HLA-B27 status, as well as hundreds of mostly unknown genetic variants of smaller effect. The aim of my research was to confirm some of the previously observed genetic associations and to identify new associations, many of which are in biological pathways relevant to AS pathogenesis, most notably the IL-23/T<sub>H</sub>17 axis (IL23R) and antigen presentation (ERAP1 and ERAP2). Studies presented in this thesis include replication and refinement of several potential associations initially identified by earlier GWAS (WTCCC-TASC, 2007 and TASC, 2010). I conducted an extended study of IL23R association with AS and undertook a meta-analysis, confirming the association between AS and IL23R (non-synonymous SNP rs11209026, p=1.5 x 10-9, OR=0.61). An extensive re-sequencing and fine mapping project, including a meta-analysis, to replicate and refine the association of TNFRSF1A with AS was also undertaken; a novel variant in intron 6 was identified and a weak association with a low frequency variant, rs4149584 (p=0.01, OR=1.58), was detected. Somewhat stronger associations were seen with rs4149577 (p=0.002, OR=0.91) and rs4149578 (p=0.015, OR=1.14) in the meta-analysis. Associations at several additional loci had been identified by a more recent GWAS (WTCCC2-TASC, 2011). I used in silico techniques, including imputation using a denser panel of variants from the 1000 Genomes Project, conditional analysis and rare/low frequency variant analysis, to refine these associations. Imputation analysis (1782 cases/5167 controls) revealed novel associations with ERAP2 (rs4869313, p=7.3 x 10-8, OR=0.79) and several additional candidate loci including IL6R, UBE2L3 and 2p16.3. Ten SNPs were then directly typed in an independent sample (1804 cases/1848 controls) to replicate selected associations and to determine the imputation accuracy. I established that imputation using the 1000 Genomes Project pilot data was largely reliable, specifically for common variants (genotype concordence~97%). However, more accurate imputation of low frequency variants may require larger reference populations, like the most recent 1000 Genomes reference panels. The results of my research provide a better understanding of the complex genetics of AS, and help identify future targets for genetic and functional studies. 616.73

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