Browsing by Author "Matyas, John R."

Now showing 1 - 5 of 5
  • Thumbnail Image
    ItemOpen Access
    Chondrocyte response to environmental stimuli in vitro
    (2004) Matthews, Jennifer Leah Kathleen; Matyas, John R.
  • Thumbnail Image
    ItemOpen Access
    Enhanced bone repair using embryonic stem cells in a mouse model of impaired fracture healing
    (2012) Taiani, Jaymi Tiffany; Matyas, John R.; Rancourt, Derrick
    Fractures that occur in osteoporotic bone typically demonstrate impaired healing or non-union of the bony ends and current treatment methods for these types of injuries are inadequate. The field of tissue engineering offers promising treatment alternatives for diseases and injuries that affect tissues with a limited capacity for repair. Embryonic stem (ES) cells offer advantages over other stem cells types in that these cells are pluripotent, possessing the ability to generate any cell type in the body, and have a high capacity for self-renewal. This thesis describes the development of a novel product for the augmentation of bone fracture repair. Using protocols previously developed by our group, we initially attempted to differentiate bioreactor-expanded ES cells into osteoblasts and chondrocytes in stirred suspension culture systems. Surprisingly, we found that the bioreactor culture environment promoted ES cell pluripotency, resulting in limited cell differentiation. Through further experimentation, we found that exposure to a collagen I extracellular matrix induced osteoblastic differentiation of ES cells with greater efficacy than medium supplementation. Furthern1ore, the cell-loaded collagen constructs formed mineralized tissue nodules following subcutaneous implantation into immune-compromised mice. Subsequently, we developed a fracture model, using both nonnal and osteoporotic mice, to test the efficacy of the constructs to contribute to bone repair at an orthotopic site in vivo. Bone formation was enhanced in the mice treated with cell-loaded collagen constructs and the implanted cells were identified at the fracture site for up to 8 weeks. The formation of a small ectopic soft tissue mass in some of the recipient mice suggests that the collagen I matrix reduced but did not eliminate the tumorigenic potential of the cells. To our knowledge, the studies presented herein are the first of their kind to demonstrate the efficacy of a stem cell therapy for fracture repair in osteoporotic bone in vivo. The findings presented in this thesis highlight the importance of using an orthotopic implantation system to test in vivo functionality of ES cell-derived cells and provide an important foundation for future studies looking to develop stem cell therapies for bone injuries in larger animal models and people.
  • Thumbnail Image
    ItemOpen Access
    The innervation of the human acetabular labrum and hip joint: an anatomic study
    (BioMed Central, 2014-02-14) Abdullah Alzaharan; Bali, Kamal; Gudena, Ravi; Railton, Pamela; Ponjevic, Dragana; Matyas, John R.; Powell, James N.
  • Thumbnail Image
    ItemOpen Access
    Molecular Basis of Articular Cartilage Boundary Lubrication: Role of PRG4 Structure & Multimerisation
    (2015-06-15) Abubacker, Saleem; Schmidt, Tannin A; Matyas, John R.
    Proteoglycan 4 (PRG4) is a mucin-like glycoprotein found in synovial fluid (SF) and at the articular cartilage surface, where it is required for joint lubrication and health. Hyaluronan (HA), a glycosaminoglycan polymer, is another SF constituent that contributes to SF’s viscosity and cartilage lubrication properties. PRG4 and HA function effectively as friction reducing boundary lubricants at a cartilage-cartilage interface, though both have been studied at other interfaces with varying results. PRG4 can exist in SF as disulfide-bonded multimers, a structurally determinant characteristic of mucins, which may be necessary for its cartilage adsorption and boundary lubricating ability. A recently developed full-length recombinant human PRG4 (rhPRG4) has demonstrated appropriate higher order structure, O-linked glycosylations, and boundary lubricating ability at the ocular surface. However, it remains unclear if this rhPRG4 is able to adsorb to and function as a cartilage boundary lubricant. The objectives of this thesis were to (1) determine the effect of different sliding interface materials on the lubricating ability of PRG4 and HA by measuring the kinetic coefficient of friction, (2i) assess the cartilage adsorption and boundary lubricating ability of disulfide-bonded PRG4 multimers and PRG4 monomers, (2ii) evaluate the cartilage boundary lubricating ability of PRG4 multimers and PRG4 monomers with HA, and (3) assess the cartilage adsorption of rhPRG4 and the in vitro cartilage boundary lubricating properties of rhPRG4, with and without HA. PRG4 demonstrated boundary lubricating function at both cartilage-cartilage and cartilage-glass interfaces, while HA demonstrated friction reducing ability only at the cartilage-cartilage interface. The inter-molecular disulfide-bonded multimeric structure of PRG4 was important for its ability to adsorb to a cartilage surface and function as a boundary lubricant. Finally, rhPRG4 demonstrated cartilage adsorption and boundary lubricating function, with and without HA, equivalent to native PRG4. Collectively, these results demonstrate the effectiveness of putative cartilage boundary lubricants can be affected by the counterface, contribute to a greater understanding of the molecular basis of articular cartilage boundary lubrication of PRG4, and provide the foundation and motivation for future clinical evaluation of rhPRG4 as a biotherapeutic treatment for osteoarthritis.
  • Thumbnail Image
    ItemOpen Access