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Diffusional Properties of Articular Cartilage

dc.contributor.advisor Guilak, Farhid
dc.contributor.advisor Jacobson, Kenneth Alan
dc.contributor.advisor Lubkin, Sharon R.
dc.contributor.advisor Setton, Lori A.
dc.contributor.advisor Truskey, George A.
dc.contributor.author Leddy, Holly Anne
dc.date.accessioned 2007-03-14T15:43:08Z
dc.date.available 2007-03-14T15:43:08Z
dc.date.issued 2007-03-14T15:43:08Z
dc.identifier.uri https://hdl.handle.net/10161/170
dc.description.abstract Articular cartilage is the connective tissue that lines joints and provides a smooth surface for articulation and shock absorption. Osteoarthritis, the progressive degeneration of cartilage, is a painful, debilitating, and widespread disease, affecting 70% of people over 65. Because cartilage is avascular, molecular transport occurs primarily via diffusion. The goal of these studies was to examine whether cartilage matrix structure and composition have a significant effect on diffusive transport. We hypothesized that diffusion is anisotropic in the surface zone of cartilage where collagen structure is aligned and densely packed. A theoretical model and experimental protocol for fluorescence imaging of continuous point photobleaching (FICOPP) were developed to measure diffusional anisotropy. Significant anisotropy was observed in ligament, a highly ordered collagenous tissue. In less ordered articular cartilage, diffusional anisotropy was dependent on site in the tissue and size of the diffusing molecule. These findings suggest that diffusional transport of macromolecules is anisotropic in collagenous tissues, with higher rates of diffusion along primary orientation of collagen fibers. We hypothesized that structural differences in the pericellular matrix of cartilage (PCM) would lead to differences in diffusive properties as compared to the surrounding extracellular matrix (ECM). We modified the scanning microphotolysis (SCAMP) technique to allow measurement of diffusion coefficients within the PCM. Diffusion coefficients in the PCM were lower than in the adjacent ECM in normal cartilage, but with early stage arthritis, the PCM diffusivity was not different from that of the ECM. These data suggest that breakdown of the PCM is an early step in arthritis development. We hypothesized that compression of cartilage would cause site‐specific diffusivity decreases and diffusional anisotropy increases. We utilized SCAMP and FICOPP to measure diffusion coefficients and diffusional anisotropy in cartilage as it was compressed. We found that diffusivity decreased and anisotropy increased with increasing strain in a site‐specific manner. These findings suggest that the high surface zone strains that lead to low diffusivity and high anisotropy will decrease transport between cartilage and synovial fluid in compressed cartilage. We have shown that matrix structure and composition have a significant effect on diffusive transport in cartilage.
dc.format.extent 16732305 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Osteoarthritis
dc.subject fluorescence imaging of continuous point photobleaching (FICOPP)
dc.subject pericellular matrix of cartilage (PCM)
dc.subject extracellular matrix (ECM)
dc.subject scanning microphotolysis (SCAMP)
dc.title Diffusional Properties of Articular Cartilage
dc.type Dissertation
dc.department Biomedical Engineering


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