Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 205-223). Also available on the Internet.

Afhandling--Aarhus tandlaegehøjskole. / Summary in Danish. Bibliography: p. 58-67.

Thesis (Ph. D.)--University of Washington, 1998. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Afhandling--Aarhus tandlaegehøjskole. / Summary in Danish. Bibliography: p. 58-67.

Thesis (Ph.D.)--York University, 2009. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 275-298). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:NR51670

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Connective tissue extracellular matrix (ECM) consists of an interwoven network of contiguous collagen fibers that inform cell activity, direct biological function, and guide tissue homeostasis throughout life. Recently, ECM analogs have emerged as a unique ex vivo culture platform for studying healthy and diseased tissues and in the latter, enabling the screening for and development of therapeutic regimen. Unfortunately, current commonly used platforms, such as tissue-culture polystyrene (TCPS) or the basement membrane matrix, Matrigel, fail to fully recapitulate the physical and biochemical properties of the ECM. Tissue-culture polystyrene is significantly stiffer than typical ECM tissues and lacks the composition and 3-dimensional architecture that is critical for ECM function. Improving upon TCPS’s shortcomings, Matrigel retains a natural ECM structure and is comprised of native biopolymers. However, it is derived from mouse sarcomas, and thus, has significant batch-to-batch variability and often contains growth factors at non-physiologic concentrations. Moreover, despite being biopolymer based, Matrigel has relatively low amounts of type I collagen and high levels of type IV collagen, and as such, compositionally does not match the predominantly type I collagen matrix intrinsic to connective tissues. Thus, it is clear that new and improved models of the ECM are needed for in vitro culture. In pursuit of developing a highly biomimetic ECM analog, the objectives of this work were three-fold— first, to fabricate collagen-based ECM analogs with nanoscale mimicry, second, to systematically optimize crosslinking protocols in order to produce a stable substrate with continuous fibrous architecture, and third, to evaluate the substrate’s biocompatibility and utility as a platform for studying biomineralization. It was hypothesized that an architecturally and chemically relevant fibrous substrate could be prepared from gelatin and provide an optimal ex vivo platform for cell culture and new therapy screening and development. Thus, the ECM analog will be collagen-like, biocompatible, consist of continuous fibers, demonstrate both viscoelastic and elastic behavior, exhibit relevant mechanical properties, and remain stable for at least 14 days at cell culture conditions. To this end, first, a “green” electrospinning method was developed for preparing fibrous meshes from gelatin, which avoids typical electrospinning solvents that present significant health risks and barriers to large scale production. Next, crosslinking methods were developed using the reactive dialdehyde, glutaraldehyde (GTA), and the naturally derived enzyme, transglutaminase (TGase). These methods stabilized the meshes for over 28 days under cell culture conditions without disrupting its biomimetic architectures and chemical properties. In addition, a third approach to mesh fabrication using gelatin methacryloyl (gelMA) was developed to overcome the shortcomings of GTA and TGase crosslinking. With gelMA, the number of crosslinking sites were customized and, by taking advantage of its ability to undergo free radical polymerization, stable fibrous meshes were prepared with reproducible architecture, chemistry, and tunable mechanical properties. Following fabrication, the biocompatibility of the meshes was evaluated through macrophage, stem cell, and differentiated cell cultures. During culture, the macrophages maintained a naïve, non-polarized state, indicating they were not triggered towards an inflammatory response by the meshes. In addition, fibrochondrocytes, a cell critical for maintaining the collagen-based matrices where ligaments attach to bone, remained viable and maintained phenotypic expression on the meshes, as evident by their enhanced proteoglycan and collagen production relative to TCPS cultures. After demonstrating biocompatibility, the gelatin platform was coupled with a synthetic matrix vesicle (SMV) system and successfully acted as a mineralization platform in the presence of human osteoblast-like cells. Additionally, the platform supported mesenchymal stem cell expansion and mineralization when cultured with an alkaline phosphate conjugated SMV. In this work, three unique methods were developed for preparing ECM analogs. These efforts led to the production of a collagen-like mesh with nano- and micro-scale cues, fibrous continuity with little batch-to-batch variability, and proven stability in both dry and wet conditions. Importantly, these meshes did not instigate any inflammatory responses and supported fibrochondrocyte, osteoblast, and stem cell culture. Furthermore, the mesh successfully functioned as a template for biomineralization using both human osteoblast-like cells and stem cells. Collectively these findings demonstrate the potential of a collagen-like ECM analog with physiological relevance for ex vivo cell culture studies; and furthermore, its potential as a high-fidelity platform for studying cell-mediated biomineralization, cell-matrix interactions, and developing new therapeutic approaches for the treatment of connective tissue disorders.

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.

"June 2003" Includes bibliographical references (leaves 408-457)