[Truncated abstract] Articular cartilage has no vascular, neural, or lymphatic supply, and hence no intrinsic capacity to self-repair following injury. These physiological limitations, combined with the inability of local chondrocytes to contribute to the repair process, translate to poor structural and functional outcomes in these troublesome defects, and osteoarthritic deterioration with time. Subsequently, many surgical therapies have been trialed to stimulate cartilage repair, but none have produced reliable outcomes. Hence, cartilage repair research has been broadened, with many investigators now focused on cell-based treatment. Smith began a revolution of autologous cell research when in 1965 she isolated chondrocytes from articular cartilage and transplanted them into fresh cartilage nodules (Smith, 1965). Since, new technologies and improved techniques have seen autologous chondrocyte implantation (ACI) widely accepted for use in clinical orthopaedics (Bentley et al., 2003; Brittberg et al., 1994; Grande et al., 1989; Peterson et al., 2002). At present, matrix-induced autologous chondrocyte implantation (MACI) is the most surgically simple form of ACI, boasting clinical outcomes comparable to any technique on the market, and far less complications compared to the first generation of ACI - periosteal ACI (Bartlett et al., 2005; Behrens et al., 2006; Gigante et al., 2006; Henderson et al., 2004; Marlovits et al., 2005; Minas, 2001; Willers et al., 2007; Zheng et al., 2007). But whilst MACI has been adopted by the orthopaedic surgeon for articular cartilage repair, many of the molecular, histological, and clinical factors governing patient outcomes are still largely understudied. Firstly we assessed the bioactivity of fibrin sealant (FS - Tisseel®), a critical component of MACI, on the migration and proliferation of human articular chondrocytes in vitro. We also looked to elucidate the associated molecular mechanisms of thrombin, a key active ingredient in FS, by examining the expression and activation of proteaseactivated receptors (PARs), established thrombin receptors. All four PAR isoforms were detected in human chondrocytes, with PAR-1 being the major isoform expressed. '...' This thesis has demonstrated biological, histological, and clinical features of the MACI technique. Our in vitro has supported the use of fibrin sealant and collagen membrane as the major material components of MACI, illustrating improved chondrocyte proliferation, migration, and chondrogenic differentiation. We have evidenced that MACI stimulates successful production of hyaline-like cartilage by 6 months, while also showing that revised and clinically failed repair tissues are predominantly hyaline-like and fibrocartilage with inferior composition. Clinically, we have documented significant improvements in patient repair structure, function, symptoms, quality of life, and satisfaction, whilst concurrently confirming sentiment within the literature regarding the importance of exercise/ rehabilitation for maximising MACI outcome. In summary, the findings presented in this thesis suggest that MACI is a biologically sound and clinically efficacious cell-based treatment option for repairing articular cartilage defects.

Thesis (Ph.D.)--Tufts University, 1999. / Submitted to the Dept. of Chemical Engineering. Includes bibliographical references. Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thesis (M.S.)--California Polytechnic State University, 2009. / Mode of access: Internet. Title from PDF title page; viewed on June 24, 2009. Major professor: Dr. Scott Hazelwood. "Presented to the faculty of the College of Engineering, California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in General Engineering." "June 2009." Includes bibliographical references (p. 72-76). Also available on microfiche.

Thesis (M.S.)--California Polytechnic State University, 2008. / Mode of access: Internet. Title from PDF title page; viewed on January 29, 2009. Major professor: Stephen Klisch, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Mechanical Engineering." "December 2008." Includes bibliographical references (p. 56-58). Also available on microfiche.

Thesis (doctoral)--Karolinska Universitet, Stockholm, 1987. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Karolinska Universitet, Stockholm, 1987. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (Ph.D.)--Drexel University, 2010. / Includes abstract and vita. Includes bibliographical references (leaves 188-218).

Thesis (M.S.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 169-186) Also available in print.

Abstract Collagens IX, a non-fibrillar collagen, and XI, a fibrillar collagen, are minor components of cartilage collagen fibrils, which form a supportive meshwork in the cartilage extracellular matrix (ECM). Collagens IX and XI are known to be present also in other tissues, including the vitreous body of the eye, the intervertebral disc, the inner ear, and various tissues during embryonic development. Collagen IX is suggested to act as a macromolecular bridge between collagen fibrils and other ECM molecules, and it may be important for the cohesive and compressive properties of cartilage, as well as the long-term stability of articular cartilage. Collagen XI is speculated to have a role in regulating the fibril diameter, and it may participate in interactions with other ECM components. However, the role of neither collagen IX nor XI has been confirmed yet. As important but minor components of the cartilage ECM, collagens IX and XI are excellent candidates for relatively mild chondrodysplasias and even milder disease phenotypes involving cartilaginous tissues, such as non-syndromic hearing loss. There are in fact many reports describing defects in the genes for collagens IX and XI in patients with a variety of chondrodysplasias, including multiple epiphyseal dysplasia, Stickler syndrome, Marshall syndrome and otospondylomegaepiphyseal dysplasia. In order to screen the minor cartilage collagen genes for mutations, it is essential to know their gene structures. Therefore, the complete structures of the human COL9A1, COL9A2 and COL11A2 genes were characterized in this study. Also, to facilitate the analysis of the 5' region of the COL11A2 gene, the cDNA and partial genomic structure of the mouse Col11a2 gene were defined. The information obtained in this study was utilized in the mutation analysis of a family with non-ocular Stickler syndrome. The COL11A2 gene was analyzed with conformation sensitive gel electrophoresis (CSGE) and sequencing, and a heterozygous single-nucleotide mutation causing a premature termination codon was found in the affected family members. Studying the effect of the mutation on the RNA revealed that the nonsense mutation caused the skipping of a 54-bp exon, presumably through a pathway called nonsense-associated altered splicing.

Abstract The study was undertaken to determine effects of unilateral masticatory function on craniofacial growth and temporomandibular joint structures in young rabbits. Right-side maxillary and mandibular molars were ground out of occlusion under general anesthesia. Macroscopic measurements were made using the skulls and mandibular halves. Articular surface inclinations were determined using photographs. Positions of articular eminences on crania were determined using machine-vision technique. Changes to extracellular matrix of condylar cartilage were studied histochemically and biochemically. Unilateral masticatory function resulted in changes in the shapes and dimensions of the mandible, maxilla and glenoid fossa. Maxillary widths, lengths of half-mandibles, and angles between the ramus and corpus were lower on the right than on the left side of each animal that had been subjected to right-side molar grinding, and in comparison with controls. As the rabbits grew, there was no recovery from the changes that had been brought about by the asymmetric function, even after occlusal function was reversed or left unmodified after a period of unilateral function. Inclinations of articular surfaces became shallower and positions of articular eminences and glenoid fossae more anterior in animals that had been subjected to molar grinding than in controls. Proteoglycan contents of condylar cartilage extracellular matrix were also affected by molar grinding: amounts of the aggregated proteoglycans in particular were low. We concluded, that the shape and the sagittal and vertical position of the articular eminence is highly adaptive to the function of the condyle process, and that there were associated alterations in the dimensions and shapes of mandible and maxilla. Unilateral masticatory function resulted in significant changes in condylar cartilage extracellular matrix. Normal occlusion and bilaterally symmetric masticatory function during early phases of growth is important for normal development of the maxilla, mandible and articular cartilage.