Title : Advances in detecting degenerative and therapeutic changes in intervertebral discs: Insights from cyclic microindentation and matrix composition analysis
Abstract:
Background/Objective:
Degenerative Disc Disease (DDD) is characterized by structural and biochemical changes that compromise the intervertebral disc (IVD)’s mechanical properties, leading to chronic pain and functional impairment. This study utilizes cyclic microindentation to investigate the impact of advanced glycation end-products (AGEs) on IVD mechanical properties and matrix composition while exploring the therapeutic potential of AGE modulation.
Methods:
Eleven lumbar spines (T12/L1–L5/S1) were analyzed using Thompson grading, fluoroscopic imaging, and dynamic microindentation. AGE accumulation was simulated via ribosylation, and its effects on annulus fibrosus (AF) and nucleus pulposus (NP) tissues were measured. Therapeutic AGE reduction was evaluated using thiazolium salts, with mechanical properties quantified post-treatment. Matrix composition was assessed for water, proteoglycan, collagen, and AGE content.
Results:
AGE accumulation disrupted NP viscoelasticity (tan delta) and AF stiffness, correlating with reduced hydration and proteoglycan functionality. Ribosylation significantly increased tissue rigidity, impairing IVD mechanical behavior. Thiazolium salt treatment effectively reduced AGE levels, restoring mechanical properties and improving matrix composition. Post-treatment samples demonstrated enhanced hydration, increased elastic modulus, and decreased viscoelastic damping.
Conclusions:
This study highlights the critical role of AGEs in driving IVD degeneration and validates cyclic microindentation as a robust tool for assessing mechanical and compositional changes. AGE modulation via thiazolium salts offers a promising therapeutic strategy for reversing AGE-induced impairments. These findings establish a foundation for developing targeted treatments to restore IVD health, with implications for advancing DDD management.
