Asif Istiak, Ahmed Suparno Bahar Moni, Tanvir R Faisal
To the best of our knowledge, this is the first study to systematically combine and sequence enzymatic degradation and a focal cartilage defect, providing mechanistic insight into their isolated and combined effects on cartilage morpho-mechanics with relevance to OA pathomechanics and early intervention strategies.
BACKGROUND: Articular cartilage degeneration arising from the complex interplay of focal defect and enzymatic degradation compromises its morpho-mechanical integrity. The lack of comprehensive characterization of this combined pathology limits our mechanistic understanding of osteoarthritis (OA) initiation and progression.
METHODS: Cylindrical osteochondral explants were harvested from six bovine knee joints and allocated into five experimental groups (n = 12 per group): intact healthy cartilage (Control), focal defect alone (Def), enzymatic degradation alone (Enz), enzymatic degradation followed by focal defect (Enz+Def), and focal defect followed by enzymatic degradation (Def+Enz). In vitro mechanical characterization was performed under three loading configurations-ramp compression, multi-step stress-relaxation, and dynamic sinusoidal loading conditions-to characterize the elastic and viscoelastic properties of each group. Semi-quantitative compositional and histological analyses were conducted using Fourier transform infrared (FTIR) spectroscopy, light, and polarized light microscopy.
RESULTS: Enzymatic degradation plays a dominant role in compromising cartilage mechanical integrity, with enzymatically degraded cartilage exhibiting substantially greater mechanical deterioration than cartilage with a focal defect alone. FTIR analysis revealed greater zone-wise collagen loss than proteoglycan depletion in Enz group. While the combined insults compromised mechanical response across all loading conditions, Enz+Def group produced the most severe reduction in compressive 79.7%p<0.001,95%CI:[58.1%,90.1%] and equilibrium 97.7%p<0.001,[95.1%,98.9%] moduli and dynamic loading capacity relative to Control.
CONCLUSION: To the best of our knowledge, this is the first study to systematically combine and sequence enzymatic degradation and a focal cartilage defect, providing mechanistic insight into their isolated and combined effects on cartilage morpho-mechanics with relevance to OA pathomechanics and early intervention strategies.