Non-enzymatic glycation of annulus fibrosus alters tissue-level failure mechanics in tension

Benjamin Werbner; Matthew Lee; Allan Lee; Linda Yang; Mohamed Habib; Aaron J Fields; Grace D O'Connell

doi:10.1016/j.jmbbm.2021.104992

Non-enzymatic glycation of annulus fibrosus alters tissue-level failure mechanics in tension

J Mech Behav Biomed Mater. 2022 Feb:126:104992. doi: 10.1016/j.jmbbm.2021.104992. Epub 2021 Nov 20.

Authors

Benjamin Werbner¹, Matthew Lee¹, Allan Lee², Linda Yang², Mohamed Habib³, Aaron J Fields⁴, Grace D O'Connell⁵

Affiliations

¹ Department of Mechanical Engineering University of California, Berkeley, USA.
² Department of Bioengineering University of California, Berkeley, USA.
³ Department of Orthopaedic Surgery University of California, San Francisco, USA; Mechanical Engineering Department Al Azhar University, Cairo, Egypt.
⁴ Department of Orthopaedic Surgery University of California, San Francisco, USA.
⁵ Department of Mechanical Engineering University of California, Berkeley, USA; Department of Orthopaedic Surgery University of California, San Francisco, USA. Electronic address: g.oconnell@berkeley.edu.

PMID: 34864399
DOI: 10.1016/j.jmbbm.2021.104992

Abstract

Advanced-glycation end products (AGEs) are known to accumulate in biological tissues with age and at an accelerated rate in patients with diabetes and chronic kidney disease. Clinically, diabetes has been linked to increased frequency and severity of back pain, accelerated disc degeneration, and an increased risk of disc herniation. Despite significant clinical evidence suggesting that diabetes-induced AGEs may play a role in intervertebral disc failure and substantial previous work investigating the effects of AGEs on bone, cartilage, and tendon mechanics, the effects of AGEs on annulus fibrosus (AF) failure mechanics have not yet been reported. Thus, the aim of this study was to determine the relationship between physiological levels of AGEs and AF tensile mechanics at two distinct loading rates. In vitro glycation treatments with methylglyoxal were applied to minimize changes in tissue hydration and induce two distinct levels of AGEs based on values measured from human AF tissues. In vitro glycation increased modulus by 48-99% and failure stress by 45-104% versus control and decreased post-failure energy absorption capacity by 15-32% versus control (ANOVA p < 0.0001 on means; range given across two loading rates and glycation levels). AGE content correlated strongly with modulus (R = 0.74, p < 0.0001) and failure stress (R = 0.70, p < 0.0001) and moderately with post-failure energy absorption capacity (R = 0.62, p < 0.0001). Failure strain was reduced by 10-17% at the high-glycation level (ANOVA p = 0.01). Tissue water content remained near or just above fresh-tissue levels for all groups. The alterations in mechanics with glycation reported here are consistent with trends from other connective tissues but do not fully explain the clinical predisposition of diabetics to disc herniation. The results from this study may be used in the development of advanced computational models that aim to study disc disease progression and to provide a deeper understanding of altered structure-function relationships that may lead to tissue dysfunction and failure with aging and disease.

Keywords: Advanced glycation end products; Aging; Annulus fibrosus; Diabetes; Intervertebral disc; Tissue failure mechanics.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Annulus Fibrosus*
Glycosylation
Humans
Intervertebral Disc Degeneration*
Intervertebral Disc Displacement*
Intervertebral Disc*

Grants and funding

R01 AR070198/AR/NIAMS NIH HHS/United States