Interferometry of chondrocytes and impact of articular cartilage
Scott, Charles Corey
Athanasiou, Kyriacos A.
Doctor of Philosophy
Osteoarthritis and the subset of post-traumatic osteoarthritis both represent the end-stage of a degenerative process that can result from an initial tissue insult, particularly from a single mechanical impact. No current treatment has been shown to slow or stop its progression. Here, two approaches are taken to understand the physiology and pathology of articular cartilage. A cellular approach develops and uses a novel imaging technique for single cells and bioactive surfaces, while a tissue approach consists of understanding the acute and temporal effects of mechanical impact. Thus, the goals of this study are two-fold: (1) to develop vertical scanning interferometry (VSI) to obtain all salient features of chondrocytes and characterize bioactive surfaces, and (2) to develop methodologies for protecting diarthrodial joints from pathologic impact loading. VSI was validated and developed to obtain three-dimensional chondrocyte and fibroblast geometries, as well as to characterize protein-coated surfaces. VSI can now be applied to an array of studies involving single cell biomechanics, surface characterization, and cell adhesion and spreading. To examine pathology, an impact instrument was built and validated to apply repeatable impacts to articular cartilage. An explant model was characterized to understand the physiologic changes articular cartilage tissue experiences in culture over four weeks. Then, the acute and temporal effects of two levels of impact were characterized, consisting of a low level impact that did not show initial gross damage and a high level impact that caused immediate surface disruption. These studies illustrated that clinically undetectable impact injuries immediately show some subtle changes in extracellular matrix (ECM) glycosaminoglycan release and gene expression, but otherwise resemble the culture controls, while the high impact level caused gross damage. However, over a four week culture period, the subclinical impact proved to have started a degeneration cascade that significantly affected the biomechanical integrity, gene expression profile, biochemical makeup of the ECM, and chondrocyte viability. Therefore, impact injuries may account for a substantial proportion of the primary osteoarthritis cases. Further, if the start of the degeneration cascade of the low impact level can be stopped or reversed when only subtle changes are occurring, osteoarthritis prevention would be possible.
Biomedical engineering; Biophysics