Tissue engineering approaches have attempted to address some of the problems associated with articular cartilage defect repair, but grafts with sufficient functional properties have yet to reach clinical practice. Mechanical loads are properly controlled in the body to maintain the functional properties of articular cartilage. This inspires the inclusion of mechanical stimulation in any in vitro production of tissue engineered constructs for defect repair. This mechanical stimulation must improve the functional properties (both biochemical and structural) of engineered articular cartilage tissue. Only a few studies have applied more than two loading types to mimic the complex in vivo load/flow conditions. The general hypothesis of the present thesis proposes that the generation of functional articular cartilage substitute tissue in vitro benefits from load and fluid flow conditions similar to those occurring in vivo. It is specifically hypothesized that application of compression, shear and perfusion on chondrocyte-seeded constructs will improve their properties. It is also hypothesized that protein production of the cell-seeded constructs can be improved in a depth-dependent manner with some loading combinations. Thus, a hydromechanical stimulator system was developed that was capable of simultaneously applying compression, shear and perfusion. Functionality of system was tested by series of short-term pilot studies to optimize some of the system parameters. In these studies, agarose-chondrocytes constructs were stimulated for 2 weeks. Then, longer-term (21- 31 days) studies were performed to examine the effects of both mechanical (compression and dynamic shear) and hydromechanical (compression, dynamic shear and fluid flow) stimulation on glycosaminoglycan and collagen production. The effects of these loading conditions were also investigated for three layers of construct to find out if protein could be localized differently depth-wise. In one of the longer-term studies, the chosen mechanical and hydromechanical stimulation conditions increased total collagen production, with higher amount of collagen for hydromechanical compared with mechanical loading condition. However, their effectiveness in increasing total glycosaminoglycan production was inconclusive with the current loading regimes. The hydromechanically stimulated construct could localize higher collagen production to the top layer compared with middle and bottom layers. Some effectiveness of hydromechanical stimulation was demonstrated in this thesis. Future studies will be directed towards further optimization of parameters such as stimulation frequency and duration as well as fluid perfusion rate to produce constructs with more glycosaminoglycan and collagen.

In order to validate the appropriate functional characteristics of cartilage, we need to systematically study and understand what constitutes normality and degradation in cartilage. This thesis provides an important step in this direction. To understand the mechanical repercussions of disruption to the matrix properties, cartilage is often artificially degraded using common enzymes. Although the process of artificial degradation does not provide an accurate representation of osteoarthritis, it can provide insight into the biomechanical properties of single matrix components by examining the behaviour of the tissue following its removal. Through histological analysis utilising the optical absorbance measurements of Safranin O stain, this work has demonstrated that for a given time and enzyme concentration, the action of Trypsin on proteoglycans is highly variable and is dependent on: * The initial distribution and concentration of proteoglycans at different depths * The intrinsic sample depth * The location in the joint space, and * The medium type. These findings provide initial data towards a mathematical model which researchers can use to optimise Trypsin treatment of articular cartilage, and therefore model degeneration in vitro with a better degree of certainty. The variability noted in the distribution and concentration of proteoglycans, and most likely the collagen network, creates a large variation in the compressive and tensile stiffness of all samples, and total failure strain energy. The average values for each of these tests indicate that a loss of proteoglycan through Trypsin treatment results in decreased compressive stiffness, increased tensile stiffness, and little change to the failure strains or total failure strain energy. Conversely, disruption to the collagen network shows increased compressive and tensile stiffness, as well as failure strain and total failure strain energy. Due to the large variation in the results for each treatment group, the average values for the treated samples fall within the range of results for normal cartilage. These values cannot therefore be used as dependable parameters to benchmark cartilage, since the parameters for artificially degraded cartilage are within the normal levels. The Yeoh and Polynomial hyperelastic laws were found to best represent the material characteristics of cartilage across the range of tested samples, regardless of differences in health and strength. The results presented here provide important insight into the biomechanical outcomes of artificial degradation and provide direction for future research in this area.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998? / Errata tipped inside back end paper. Bibliography: leaves 150-190.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Levenston, Marc; Committee Member: Garcia, Andres; Committee Member: Koros, William; Committee Member: Sambanis, Athanassios; Committee Member: Temenoff, Johnna; Committee Member: Vidakovic, Brani.

Thesis (Ph.D)--Chemical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Boyan, Barbara; Committee Chair: Wick, Timothy; Committee Member: Brockbank, Kelvin; Committee Member: Nenes, Athanasios; Committee Member: Sambanis, Athanassios. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Boyan, Barbara; Committee Member: Bonassar, Lawrence; Committee Member: Sambanis, Anthanassios; Committee Member: Schwartz, Zvi; Committee Member: Wick, Timothy.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2007" Includes bibliographical references.

Thesis (Ph. D.)--Bioengineering, Georgia Institute of Technology, 2006. / Harish Radhakrishna, Committee Member ; Christopher Jacobs, Committee Member ; Andres Garcia, Committee Member ; Marc E. Levenston, Committee Chair ; Barbara Boyan, Committee Member.