Multimodal characterization of articular cartilage degeneration in the humeral head using Raman spectroscopy, biomechanics, and imaging

This study evaluated articular cartilage degeneration in the humeral head using a multimodal approach integrating Raman spectroscopy, mechanical testing, biochemical analysis, and micro-computed tomography (µCT). The goal was to identify sensitive biomarkers of early matrix-level degeneration that precede overt radiographic changes in glenohumeral osteoarthritis (OA). Eleven humeral heads were collected from cadaveric shoulders and stratified by the presence of a focal chondral defect and rotator cuff (RC) tear status, yielding four specimens without visual cartilage degeneration (controls) and seven samples (3 RC + OA, 4 OA Only) with visual defects. Raman spectroscopy was used to non-destructively quantify the contents of cartilage glycosaminoglycan (GAG), collagen (COL), and water (HO). Tissue stiffness was assessed via indentation mechanical testing, and biochemical composition was assessed via DMMB (GAG) and OHP (COL) assays and gravimetric HO content. µCT imaging quantified trabecular bone architecture. Cartilage from degenerated regions exhibited decreased mechanical stiffness with a corresponding reduction in GAG and an increase in tissue hydration. Raman-derived GAGaccounted for 68% of the variation in indentation modulus and outperformed conventional Outerbridge grading in identifying tissue with compromised mechanical function. µCT revealed thinning of subchondral trabeculae in areas adjacent to cartilage degeneration. Cartilage degeneration in the glenohumeral joint is characterized by extracellular matrix (ECM) loss, increased hydration, compromised mechanical function, and alterations to the trabecular structure. Raman spectroscopy enabled the production of non-destructive spatial maps of tissue ECM composition, highlighting the progressive OA-associated changes in specimens with and without focal defects.