Annulus Fibrosus Micro-Damage in MILD Intervertebral Disc Degeneration

Parisa Akhlaghi; Remco Doodkorte; Peter Lafranca; Tom Schlösser; Bert van Rietbergen; Keita Ito

doi:10.1016/j.spinee.2025.10.005

Annulus Fibrosus Micro-Damage in MILD Intervertebral Disc Degeneration

Parisa Akhlaghi
, Remco Doodkorte
, Peter Lafranca
, Tom Schlösser
, Bert van Rietbergen
, Keita Ito (Corresponding author)

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND CONTEXT: Degeneration of the intervertebral discs (IVDs) causes significant biomechanical changes and structural defects, often leading to pain or disability. These defects impair both the biomechanics and physiology of the IVD, contributing to further structural failure of the IVD. Although the function and structure of the annulus fibrosus (AF) affect overall disc function, its structural change during degeneration is not fully characterized.

PURPOSE: The objective of this study was to investigate AF microdamage and mechanical function in mildly degenerated discs.

STUDY DESIGN: Basic laboratory study using human cadaveric intervertebral discs.

METHODS: Microdamage and its functional implications in the AF of human IVDs with mild degeneration were assessed through a comprehensive approach focusing on biomechanical, and structural analyses. Eighteen fresh-frozen human cadaveric discs (T10-L5, n=3 spines, 43-58 years old) were analyzed from anterior, posterior, and lateral regions of the inner and outer AF. Collagen microdamage was assessed using Collagen Hybridizing Peptide (CHP), and Second Harmonic Generation (SHG) imaging to provide high-resolution insights into collagen fiber structure. Mechanical testing was performed on the same regions.

RESULTS: Damage analyses showed no significant differences between the degenerative grades except in the posterior outer AF, where grade 3 discs showed higher CHP and SHG signal intensity compared to grade 2. Plus, mechanical properties did not differ significantly between the grades, although large variances were observed, particularly in the posterior outer AF.

CONCLUSIONS: Despite limited mechanical differences, early structural damage was found in the posterior outer AF. This indicates that this part is the initial site of AF damage and biological response during IVD degeneration.

CLINICAL SIGNIFICANCE: These findings highlight the posterior outer AF as a potential target for early diagnostic and therapeutic interventions to mitigate further degeneration and preserve disc function.

Original language	English
Journal	The Spine Journal
Volume	XX
DOIs	https://doi.org/10.1016/j.spinee.2025.10.005
Publication status	Accepted/In press - 10 Oct 2025

Bibliographical note

Funding

Author disclosures: PA: Grant: European Research Council (I, Paid directly to institution/employer). RD: Nothing to disclose. PL: Grant: European Research Council (I, Paid directly to institution/employer); Research Support (Investigator Salary, Staff/Materials): UMC Utrecht (D); Grants: Scoliosis Research Society (D, Paid directly to institution/employer). TS: Speaking and/or Teaching Arrangements: MBA Healthcare J&J (A, Paid directly to institution/employer); Board of Directors: EUROSPINE board (A, Paid directly to institution/employer); Grants: SRS (C, Paid directly to institution/employer), Raak publiek (B, Paid directly to institution/employer), Health holland (G, Paid directly to institution/employer). BVR: Consulting: Amolyt Pharma (E, Paid directly to institution/employer). KI: Grant: European Research Council (I, Paid directly to institution/employer); Scientific Advisory Board/Other Office: NC Biomatrix BV (E), Orthopaedic Research Society (journal editorship) (C), Dutch Research Council (committees) (A). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 101020004 , ScoliStorm).

Funders	Funder number
Universitair Medisch Centrum Utrecht
European Union's Horizon 2020 - Research and Innovation Framework Programme	101020004

Keywords

Annulus fibrosus
Collagen hybridizing Peptide
Degeneration
Intervertebral Disc
Microdamage
Second harmonic generation

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10.1016/j.spinee.2025.10.005

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@article{6325861a696a4465b517dbe6a5441113,

title = "Annulus Fibrosus Micro-Damage in MILD Intervertebral Disc Degeneration",

abstract = "BACKGROUND CONTEXT: Degeneration of the intervertebral discs (IVDs) causes significant biomechanical changes and structural defects, often leading to pain or disability. These defects impair both the biomechanics and physiology of the IVD, contributing to further structural failure of the IVD. Although the function and structure of the annulus fibrosus (AF) affect overall disc function, its structural change during degeneration is not fully characterized.PURPOSE: The objective of this study was to investigate AF microdamage and mechanical function in mildly degenerated discs.STUDY DESIGN: Basic laboratory study using human cadaveric intervertebral discs.METHODS: Microdamage and its functional implications in the AF of human IVDs with mild degeneration were assessed through a comprehensive approach focusing on biomechanical, and structural analyses. Eighteen fresh-frozen human cadaveric discs (T10-L5, n=3 spines, 43-58 years old) were analyzed from anterior, posterior, and lateral regions of the inner and outer AF. Collagen microdamage was assessed using Collagen Hybridizing Peptide (CHP), and Second Harmonic Generation (SHG) imaging to provide high-resolution insights into collagen fiber structure. Mechanical testing was performed on the same regions.RESULTS: Damage analyses showed no significant differences between the degenerative grades except in the posterior outer AF, where grade 3 discs showed higher CHP and SHG signal intensity compared to grade 2. Plus, mechanical properties did not differ significantly between the grades, although large variances were observed, particularly in the posterior outer AF.CONCLUSIONS: Despite limited mechanical differences, early structural damage was found in the posterior outer AF. This indicates that this part is the initial site of AF damage and biological response during IVD degeneration.CLINICAL SIGNIFICANCE: These findings highlight the posterior outer AF as a potential target for early diagnostic and therapeutic interventions to mitigate further degeneration and preserve disc function.",

keywords = "Annulus fibrosus, Collagen hybridizing Peptide, Degeneration, Intervertebral Disc, Microdamage, Second harmonic generation",

author = "Parisa Akhlaghi and Remco Doodkorte and Peter Lafranca and Tom Schl{\"o}sser and \{van Rietbergen\}, Bert and Keita Ito",

note = "Copyright {\textcopyright} 2025. Published by Elsevier Inc.",

year = "2025",

month = oct,

day = "10",

doi = "10.1016/j.spinee.2025.10.005",

language = "English",

volume = "XX",

journal = "The Spine Journal",

issn = "1529-9430",

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TY - JOUR

T1 - Annulus Fibrosus Micro-Damage in MILD Intervertebral Disc Degeneration

AU - Akhlaghi, Parisa

AU - Doodkorte, Remco

AU - Lafranca, Peter

AU - Schlösser, Tom

AU - van Rietbergen, Bert

AU - Ito, Keita

PY - 2025/10/10

Y1 - 2025/10/10

N2 - BACKGROUND CONTEXT: Degeneration of the intervertebral discs (IVDs) causes significant biomechanical changes and structural defects, often leading to pain or disability. These defects impair both the biomechanics and physiology of the IVD, contributing to further structural failure of the IVD. Although the function and structure of the annulus fibrosus (AF) affect overall disc function, its structural change during degeneration is not fully characterized.PURPOSE: The objective of this study was to investigate AF microdamage and mechanical function in mildly degenerated discs.STUDY DESIGN: Basic laboratory study using human cadaveric intervertebral discs.METHODS: Microdamage and its functional implications in the AF of human IVDs with mild degeneration were assessed through a comprehensive approach focusing on biomechanical, and structural analyses. Eighteen fresh-frozen human cadaveric discs (T10-L5, n=3 spines, 43-58 years old) were analyzed from anterior, posterior, and lateral regions of the inner and outer AF. Collagen microdamage was assessed using Collagen Hybridizing Peptide (CHP), and Second Harmonic Generation (SHG) imaging to provide high-resolution insights into collagen fiber structure. Mechanical testing was performed on the same regions.RESULTS: Damage analyses showed no significant differences between the degenerative grades except in the posterior outer AF, where grade 3 discs showed higher CHP and SHG signal intensity compared to grade 2. Plus, mechanical properties did not differ significantly between the grades, although large variances were observed, particularly in the posterior outer AF.CONCLUSIONS: Despite limited mechanical differences, early structural damage was found in the posterior outer AF. This indicates that this part is the initial site of AF damage and biological response during IVD degeneration.CLINICAL SIGNIFICANCE: These findings highlight the posterior outer AF as a potential target for early diagnostic and therapeutic interventions to mitigate further degeneration and preserve disc function.

AB - BACKGROUND CONTEXT: Degeneration of the intervertebral discs (IVDs) causes significant biomechanical changes and structural defects, often leading to pain or disability. These defects impair both the biomechanics and physiology of the IVD, contributing to further structural failure of the IVD. Although the function and structure of the annulus fibrosus (AF) affect overall disc function, its structural change during degeneration is not fully characterized.PURPOSE: The objective of this study was to investigate AF microdamage and mechanical function in mildly degenerated discs.STUDY DESIGN: Basic laboratory study using human cadaveric intervertebral discs.METHODS: Microdamage and its functional implications in the AF of human IVDs with mild degeneration were assessed through a comprehensive approach focusing on biomechanical, and structural analyses. Eighteen fresh-frozen human cadaveric discs (T10-L5, n=3 spines, 43-58 years old) were analyzed from anterior, posterior, and lateral regions of the inner and outer AF. Collagen microdamage was assessed using Collagen Hybridizing Peptide (CHP), and Second Harmonic Generation (SHG) imaging to provide high-resolution insights into collagen fiber structure. Mechanical testing was performed on the same regions.RESULTS: Damage analyses showed no significant differences between the degenerative grades except in the posterior outer AF, where grade 3 discs showed higher CHP and SHG signal intensity compared to grade 2. Plus, mechanical properties did not differ significantly between the grades, although large variances were observed, particularly in the posterior outer AF.CONCLUSIONS: Despite limited mechanical differences, early structural damage was found in the posterior outer AF. This indicates that this part is the initial site of AF damage and biological response during IVD degeneration.CLINICAL SIGNIFICANCE: These findings highlight the posterior outer AF as a potential target for early diagnostic and therapeutic interventions to mitigate further degeneration and preserve disc function.

KW - Annulus fibrosus

KW - Collagen hybridizing Peptide

KW - Degeneration

KW - Intervertebral Disc

KW - Microdamage

KW - Second harmonic generation

UR - https://www.scopus.com/pages/publications/105023880834

U2 - 10.1016/j.spinee.2025.10.005

DO - 10.1016/j.spinee.2025.10.005

M3 - Article

C2 - 41077077

SN - 1529-9430

VL - XX

JO - The Spine Journal

JF - The Spine Journal

ER -

Annulus Fibrosus Micro-Damage in MILD Intervertebral Disc Degeneration

Abstract

Bibliographical note

Funding

Keywords

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