Articular cartilage is a type of hyaline cartilage that covers the ends of long bones. This special type of tissue provides a smooth, lubricated gliding surface for joints, and is also responsible for load-bearing during movements. Intact and healthy articular cartilage is essential for the mobility of mammals. Osteoarthritis (OA) is a degenerative disease that affects the whole joint, in particular, the articular cartilage. During disease progression cartilage is gradually degraded by enzymes released during tissue inflammation as well as mechanical friction. One of the indicators that appears at the earliest OA stage is the loss of glycosaminoglycans (GAGs). Current diagnoses of this disease are mainly based on X-ray or MRI scans, but neither of these techniques can detect OA at its early stage, which would be required to intervene and slow the disease progression. Raman microscopy is a technique that can provide compositional information about native cartilage, providing a non-destructive technique that can generate high-resolution spatial maps. However, the reported methods still require sample sectioning.

In this thesis, confocal Raman microscopy was applied to study the degradation of cartilage, specifically focused on the loss of proteoglycans. A cartilage degradation model was established by trypsin digestion of cartilage samples. I used histology, biochemical analysis, and confocal Raman microscopy to characterize the chemical content and distribution within the cartilage samples. Two different confocal Raman mapping techniques, cross-section scan and depth scan, were applied. I found that Raman microscopy is capable of detecting GAG degradation, and the chondroitin sulfate (CS) coefficient maps can provide distributions similar to histology. The depth scans, during which subsurface data were collected without sectioning the samples, were also found to generate spectra and distributions consistent with Raman scans of the surface-to-bone cross sections. Both methods demonstrated higher GAG content at the deeper zone beneath the articular surface and showed negligible GAG content for fully digested tissue. The measurements on partially digested cartilage concluded that both Raman scanning methods have the sensitivity to detect zonal GAG degradation of ~100 μm scale. This research provides a technique to non-invasively measure cartilage degradation using confocal Raman microscopy, which lays a foundation for potential in vivo measurements and OA diagnosis.