Abstract
The study of osteoarthritis (OA) – a painful and disabling disease characterized by disruption and loss of articular cartilage – is challenged by the fact that in most cases clinically recognizable signs and symptoms appear late in the osteoarthritic process, at which point structural and mechanical changes are already quite advanced. Consequently, the critical early events that occur when the disease process is potentially reversible are still not well defined. Although many of the exact details of the early natural history of OA are still unknown, clinical and experimental evidence suggest a degenerative progression beginning with disruption of the extracellular network at the articular surface. Since the articular surface cartilage has an important role in governing the mechanical behavior of the tissue, a better understanding of the early structural and mechanical changes of the cartilage surface that precede overt fibrillation and cartilage thinning would help to characterize the initiating pathogenic events in OA.
The studies in this thesis support the presence of a discrete surface lamina and reveal distinct biochemical, structural and mechanical changes in this region in the early phases of experimental osteoarthritis. Micromechanical analyses reveal dramatic reductions in material properties of the articular surface in injured cartilage compared to contralateral controls including reductions in indentation moduli of up to six-fold; a decrease in the ratio of elastic vs. viscous material behavior; and an increase in surface friction coefficients under nanonewton-level applied normal forces. Changes in mechanical properties were associated with disintegration of the articular surface indicated by cracking and roughening of the cartilage surface and reduced fibrillar organization and thinning of the superficial zone.
These analyses contribute to a better understanding of the depth- and scale-dependent properties of cartilage in health and disease. The mechanical data define a range of microscale structural and mechanical properties that can potentially be used as targets and inputs for: (1) repair tissues and tissue-engineered constructs for OA treatment; (2) clinical functional diagnostic tests of cartilage integrity; and (3) microscale and hierarchical computational models of cartilage force-deformation behavior.
