Raman-probe-derived biomarkers account for cartilage composition, structure, and viscoelastic properties

Raman spectroscopy is an inelastic light scattering technique that reflects the vibrational modes of the biochemical building blocks of the major constituents that comprise the cartilage extracellular matrix (ECM): glycosaminoglycans (GAG), type-II collagen (COL), and water. We investigated whether ECM-specific biomarkers measured with our recently developed arthroscopy-compatible Raman needle probe characterize the functional viscoelastic properties of articular cartilage explants. Equine osteochondral explants were harvested from high-load (femoral condyle) and low-load (intertrochlear groove) sites to evaluate Raman-derived biomarkers of cartilage structure and function. Viscoelastic material properties (equilibrium/dynamic modulus, phase shift) were determined by mechanical indentation. A computational fibril-reinforced biphasic material model was used to estimate the glycosaminoglycan-associated non-fibrillar-matrix modulus, the collagen-associated fibril-network modulus, and hydraulic permeability. Raman-derived biomarkers enabled evaluation of cartilage tissue composition and structure, accounting for 81% of the variation in GAG content, 53% of the variation in COL content, and 58% of the variation in COL anisotropy. Biomarkers also accounted for 81% of the variation in equilibrium modulus, 58% in dynamic modulus, and 51% in phase shift. For poroelastic properties, biomarkers accounted for 83% of the variation in non-fibrillar-matrix modulus, 25% of the variation in fibril-network modulus, and 34% of the variation in hydraulic permeability. Clinical Significance: Raman spectroscopy provides objective compositional biomarkers that account for viscoelastic material properties underlying articular cartilage function. These findings support its future use as an arthroscopic platform for objective assessment of cartilage injury, monitoring of disease progression, and evaluation of therapeutic interventions.