Thesis (M. Phil.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 92-108) Also available in print.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--University of Michigan, 1976.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--University of Michigan, 1976.

Connective tissue initially arises from embryonic mesenchymal stem cells (MSC) that originate from the mesoderm during embryogenesis and are capable of differentiating into connective tissue lineages such as adipocytes, osteoblasts, chondrocytes and fibroblasts. Connective tissue is composed of cells held together by the extracellular matrix (ECM). The fibrillins and latent transforming growth factor binding proteins form a superfamily of ECM proteins characterised by the presence of a unique domain, the 8- cysteine transforming growth factor beta binding domain (TGFß). The fibrillin proteins (fibrillin-1, fibrillin-2 and fibrillin-3 in most vertebrates, encoded by the FBN1, FBN2 and FBN3 genes respectively), are major components of the 10nM microfibrils found in ECM of many tissue types, for example mesenchyme-derived connective tissues. Fibrillin-1 and fibrillin-2 are also thought to be required for stabilization and storage of latent TGFβ complexes. Mutations in FBN1 cause Marfan syndrome, a connective tissue disorder characterised by abnormalities in the microfibrils resulting in musculoskeletal, ocular, cardiovascular and other complications. FBN2 mutations lead to congenital contractural arachnodactyly, which has a musculoskeletal phenotype similar to Marfan syndrome. There are currently no known diseases associated with FBN3 mutations. In this project, the expression of fibrillins was investigated using human cell lines during early development, mesenchymal stem cell differentiation and in further differentiated mesenchymal cell lines, for example in osteocytes (osteosarcomas), chondrocytes and fibroblast lineage. Immunocytochemistry was used to examine protein expression, real-time PCR and expression microarrays to determine mRNA synthesis and RNAi suppression of gene expression to determine possible functions of fibrillins and associated ECM proteins. In addition, a genome wide bioinformatics evaluation was performed of transcription start sites for the fibrillin gene family utilising the information obtained from the FANTOM5 consortium. The three fibrillin genes showed differing expression patterns in cell lines depending on the stage of development/differentiation. During embryogenesis, expression of FBN3, FBN2 and FBN1 increased sequentially in that order. Expression of FBN3 followed the same pattern as expression of known pluripotency markers, while expression of FBN2 correlated with expression of markers for later stages of mesoderm differentiation. FBN1 expression was associated with mesenchymal markers, and this was supported by a study of mesenchymal stem cells differentiation to the adipose lineage. Fibrillin-1 microfibrils and RNA expression were present early in primary adult human MSC differentiating to adipocytes, suggesting that a fibrillin matrix is required for initial MSC attachment. As differentiation proceeded, fibrillin -1 expression decreased, with rapid degradation of the microfibrils. Fibrillin-2 expression increased following differentiation and fibrillin-3 was not expressed. These results suggest that fibrillin-1 plays an important structural and regulatory role in the early stages of connective tissue development but is not required to maintain the differentiated state. Many genes showed the same expression pattern as FBN1. To better understand the importance of fibrillin-1 and its interaction with these coexpressing genes, fibrillin-1 was knocked down using siRNA in fibroblast, chondrocyte and osteosarcoma cell lines. There were little to no effects identified in chondrocyte and osteosarcoma cell lines, and only a few genes were altered following the reduction of fibrillin-1 mRNA in fibroblasts, suggesting that fibrillin-1 is not a central regulator but an endpoint. This was surprising given its potential role in controlling bioavailability of TGFβ, a key regulator of mesenchymal cells. In addition, the evolution of the fibrillin gene family was studied and it was found that the gene structure, amino acid sequence and genomic positions of each gene are widely conserved across vertebrates, suggesting an important role in vertebrate body structure. However, the differences in gene structure and sequence between the three fibrillin genes suggest divergent function. Fibrillin-1 mutations with the most severe phenotypes are located in regions that are highly conserved. This study shows that there is a clear developmental and evolutionary distinction between the three fibrillins. Fibrillin-3 was associated with pluripotency and its presence in differentiating foetal liver and brain may suggest that there are residual pluripotent cells in these developing tissues. Fibrillin-2 appeared to be a marker for the mesodermal stage and its role in adult cells is currently not clear. Fibrillin-1 was present in cells already predetermined to go to mesenchymal lineages, but it was minimal in the advanced stages of differentiation suggesting that it may be a marker for relatively plastic mesenchymal cells prior to commitment to a specific lineage. These results will assist in the understanding of disorders resulting from fibrillin gene mutations and have identified coexpressed proteins, potential modifiers that could be the targets of gene therapy and candidates for similar connective tissue.

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No description available.

As a good and competent surgical simulator, it should provide surgeons with visual, tactile and behavioral illusion of reality. In literature, methods for object deformation range from non-physically based models to physically based models. Early works of non-physically based models focused on pure geometrical models that were originally employed in computer-aided design. These methods could be used to produce vivid deformable effects in computer animation. However, the soft tissue simulation in surgical applications requires more realistic models based on physical properties of human tissues. As a result, the mass-spring model and the finite element model have become the most popular representations for deformable organs in surgical simulation. Our research focuses on the real-time soft tissue deformable model based on the finite element method for surgical application. / Extended from the hybrid condensed finite element model, an interactive hybrid condensed model with hardware acceleration by the graphics processing unit (GPU) is proposed. Two methods are developed in order to map the data onto the GPU in accordance with the application data structure. The performance of the primary calculation task in the solver is enhanced. Furthermore, an improved scheme is presented to conduct the newly applied forces induced by dragging or poking operations in the non-operational region. / In the thesis, new approaches to establish a physically based model for soft tissue deformation and cutting in virtual-reality-based simulators are proposed. A deformable model, called the hybrid condensed finite element model, based on the volumetric finite element method is presented. By this method, three-dimensional organs can be represented as tetrahedral meshes, divided into two regions: the operational region and the non-operational one. Different methods treat the regions with different properties in order to balance the computational time and the level of the simulation realism. The condensation technique is applied to only involve the calculation of the surface nodes in the non-operational region while the fully calculation of the volumetric deformation is processed in the operational part. This model guarantees the smooth simulation of cutting operation with the exact cutting path when users manipulate a virtual scalpel. Moreover, we discuss the relevant aspects on what affect the efficiency of implementing the finite element method, as well as the issues considered for choosing the effective solving method to our problem. Three numerical methods have been examined in our model. / Surgical simulator, which benefits from virtual reality techniques, presents a realistic and feasible approach to train inexperienced surgeons within a safe environment. It plays more and more important role in medical field and also changes the world of surgical training. Especially, the minimally invasive microsurgery, which offers patients various attractive advantages over the traditional surgery, has been widely used in otolaryngology, gastroenterology, gynecology and neurology in the last two decades. / Through the combination of these approaches, a physically based model which allows users to freely perform the soft tissue cutting and detecting, such as poking or dragging operations, with soft tissue deformation is achieved in real-time. / Wu Wen. / "August 2006." / Adviser: Pheng Ann Heng. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1745. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 112-127). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell therapies to stimulate endogenous cartilage regeneration has gained momentum. Adipose stem cells (ASCs) are an attractive option for this endeavor because of their accessibility, chondrogenic potential, and secretion of factors that promote connective tissue repair. In order to use the factors secreted by ASCs to stimulate cartilage regeneration, the signaling pathways that affect postnatal cartilage development and morphology need to be understood. Next, approaches need to be developed to tailor the secretory profile of ASCs to promote cartilage regeneration. Finally, delivery methods that localize ASCs within a defect site while facilitating paracrine factor secretion need to be optimized. The overall objective of this thesis was to develop an ASC therapy that could be effectively delivered in cartilage defects and stimulate regeneration via its paracrine actions. The general hypothesis was that the secretory profile of ASCs can be tailored to enhance cartilage regeneration and be effectively delivered to regenerate cartilage in vivo. The overall approach used the growth plate as an initial model to study changes in postnatal cartilage morphology and the molecular mechanisms that regulate it, different media treatments and microencapsulation to tailor growth factor production, and alginate microbeads to deliver ASCs in vivo to repair cartilage focal defects.