Advances in detecting degenerative and therapeutic changes in intervertebral discs: Insights from cyclic microindentation and matrix composition analysis
Kaan Sevgi1, Simon Tang2
, Sinan Aran3
1Kansas City University of Medicine & Biosciences, School of Medicine, Kansas City, United States
2Department of Orthopaedic Surgery, Washington University, St. Louis, USA
3Department of Family Medicine, Demiroğlu Science University, İstanbul, Türkiye
Keywords: Advanced glycation end-products, cyclic microindentation, degeneration, intervertebral disc, thiazolium salts.
Abstract
Objectives: This study aimed to evaluate degenerative and therapeutic changes in intervertebral discs (IVDs) using cyclic microindentation and matrix composition analysis, focusing on the role of advanced glycation end-products (AGEs) in altering mechanical and biochemical properties.
Patients and methods: Between March 2023 and October 2023 a total of 11 lumbar spines (T12/L1–L5/S1) from donor sample (5 males, 6 females; mean age of 82.5±10.2 years; range, 63 to 99 years) were included in the study. Intervertebral disc degeneration was graded using Thompson criteria and confirmed via fluoroscopy. Cyclic microindentation quantified elastic modulus and tan delta (viscoelastic damping) under in vitro ribosylation to simulate AGE accumulation. Thiazolium salts were applied to assess therapeutic effects. Matrix composition was evaluated for water, proteoglycan, collagen, and AGE content, with statistical analyses correlating mechanical and biochemical changes.
Results: Ribosylation increased AGE levels, significantly reducing viscoelasticity in nucleus pulposus (NP) tissues and stiffness in annulus fibrosus (AF) tissues. Advanced glycation end-products accumulation disrupted proteoglycan functionality and hydration, exacerbating degeneration. Thiazolium salt treatment reduced AGE levels, improving NP viscoelasticity, AF stiffness, and hydration. Correlation analyses demonstrated significant relationships between AGE levels, mechanical properties, and matrix composition.
Conclusion: Cyclic microindentation effectively identified AGE-induced mechanical impairments in IVD tissues. Advanced glycation end-products accumulation plays a critical role in IVD degeneration by altering matrix composition and mechanical behavior. Thiazolium salts reversed these changes, highlighting AGE modulation as a promising therapeutic strategy. Future research should integrate advanced imaging and in vivo studies to optimize AGE-targeted therapies for degenerative disc disease.
Cite this article as: Sevgi K, Tang S, Aran S. Advances in detecting degenerative and therapeutic changes in intervertebral discs: Insights from cyclic microindentation and matrix composition analysis. D J Med Sci 2025;11(1):1-9. doi: 10.5606/fng.btd.2025.173.
Conceptualized the study, conducted literature review, drafted and revised the manuscript, and contributed to figure/table development and data interpretation, acquisition and collection of all raw data, sample processing, and laboratory testing procedures: K.S.; Verified and submitted all original data to the research team and bears full responsibility for the integrity and accuracy of the data presented: S.T.; Supervised the manuscript development, reviewed and edited final drafts for intellectual content, and provided guidance on clinical interpretation and discussion: S.N.A.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.