Riboflavin-sensitized UVA collagen crosslinking produced a controllable, dose-dependent increase in the nanomechanical strength of ex vivo bovine dura mater
8 affiliations
- 1Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany
- 2Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 3CAST, Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany
- 4Laboratory of Experimental Brain & Spine Surgery (LENS), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 5Department of Neurosurgery, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 6Berta-Ottenstein-Program for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 7Neuroelectronic Systems, Department of Neurosurgery, Medical Center - University of Freiburg, Freiburg, Germany
- 8Institute of Analytical and Bioanalytical Chemistry, Ulm University, Ulm, Germany
Abstract
Background: Dural defects, either from trauma, tumor resection, surgical approaches, genetics, or spontaneously represent a significant clinical challenge in neurosurgery. Given the established efficacy of riboflavin-sensitized ultraviolet-A (UVA) photo-crosslinking in ophthalmology, this study investigated its feasibility and dose-response characteristics as a novel strategy to biochemically augment the mechanical integrity and strength of ex-vivo bovine dura mater. Methods: Forty bovine dura mater specimens were treated ex vivo using riboflavin concentrations of 2, 4, or 8 mM combined with UVA irradiation at 0.3 or 3 mW/cm2. PBS-treated specimens exposed to UVA served as controls. Atomic force microscopy nanoindentation was used to measure the local elastic modulus in matched regions before and after treatment, enabling paired assessment of treatment-induced mechanical changes while minimizing inter-sample variability. Post-treatment stiffness, fold-change from baseline, and riboflavin dose-response relationships were analyzed statistically. Results: Baseline elastic moduli were equivalent across all groups (mean approximately 52 kPa, p = 0.92). While UVA alone caused a modest approximately 2- to 3-fold stiffness increase, riboflavin-UVA treatment produced a dramatic, concentration-dependent effect. The highest treatment (8 mM RF, 3 mW/cm2 UVA) increased the elastic modulus 150-fold, from approximately 53 kPa to approximately 8,000 kPa. Post-UV stiffness exhibited a strong linear relationship with riboflavin concentration (R2 = 0.994), indicating a precisely titratable crosslinking effect. All treatment conditions were statistically distinguishable (p < 0.001). Conclusion: Riboflavin-sensitized UVA crosslinking substantially increases the nanomechanical strength of ex vivo bovine dura mater in a controllable, dose-dependent manner. These findings establish a proof of concept for biochemical reinforcement of dural tissue that might be used clinically. As a next step evaluation using human dura, macroscopic biomechanical testing, penetration-depth analysis, and safety assessment is warranted.
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BibTeX
@article{vasilikos2026riboflavinsensitized,
title = {{Riboflavin-sensitized UVA collagen crosslinking produced a controllable, dose-dependent increase in the nanomechanical strength of ex vivo bovine dura mater}},
author = {Ioannis Vasilikos and Sukesh Mysore Swamy and Ulrich G. Hofmann and Ulrich Hubbe and Roland Rölz and Angeliki Stathi and Katerina Wolk and Daniel Strahnen and Amir El Rahal and Mukesch J. Shah and Jürgen Grauvogel and Florian Volz and Boris Mizaikoff and Lorena Diaz and Vidhya M. Ravi and Kevin Joseph and Jürgen Beck},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0351819},
url = {https://doi.org/10.1371/journal.pone.0351819},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Riboflavin-sensitized UVA collagen crosslinking produced a controllable, dose-dependent increase in the nanomechanical strength of ex vivo bovine dura mater
AU - Ioannis Vasilikos
AU - Sukesh Mysore Swamy
AU - Ulrich G. Hofmann
AU - Ulrich Hubbe
AU - Roland Rölz
AU - Angeliki Stathi
AU - Katerina Wolk
AU - Daniel Strahnen
AU - Amir El Rahal
AU - Mukesch J. Shah
AU - Jürgen Grauvogel
AU - Florian Volz
AU - Boris Mizaikoff
AU - Lorena Diaz
AU - Vidhya M. Ravi
AU - Kevin Joseph
AU - Jürgen Beck
PY - 2026
DA - 2026/09/28
JO - PLOS One
DO - 10.1371/journal.pone.0351819
UR - https://doi.org/10.1371/journal.pone.0351819
AB - Background: Dural defects, either from trauma, tumor resection, surgical approaches, genetics, or spontaneously represent a significant clinical challenge in neurosurgery. Given the established efficacy of riboflavin-sensitized ultraviolet-A (UVA) photo-crosslinking in ophthalmology, this study investigated its feasibility and dose-response characteristics as a novel strategy to biochemically augment the mechanical integrity and strength of ex-vivo bovine dura mater. Methods: Forty bovine dura mater specimens were treated ex vivo using riboflavin concentrations of 2, 4, or 8 mM combined with UVA irradiation at 0.3 or 3 mW/cm2. PBS-treated specimens exposed to UVA served as controls. Atomic force microscopy nanoindentation was used to measure the local elastic modulus in matched regions before and after treatment, enabling paired assessment of treatment-induced mechanical changes while minimizing inter-sample variability. Post-treatment stiffness, fold-change from baseline, and riboflavin dose-response relationships were analyzed statistically. Results: Baseline elastic moduli were equivalent across all groups (mean approximately 52 kPa, p = 0.92). While UVA alone caused a modest approximately 2- to 3-fold stiffness increase, riboflavin-UVA treatment produced a dramatic, concentration-dependent effect. The highest treatment (8 mM RF, 3 mW/cm2 UVA) increased the elastic modulus 150-fold, from approximately 53 kPa to approximately 8,000 kPa. Post-UV stiffness exhibited a strong linear relationship with riboflavin concentration (R2 = 0.994), indicating a precisely titratable crosslinking effect. All treatment conditions were statistically distinguishable (p < 0.001). Conclusion: Riboflavin-sensitized UVA crosslinking substantially increases the nanomechanical strength of ex vivo bovine dura mater in a controllable, dose-dependent manner. These findings establish a proof of concept for biochemical reinforcement of dural tissue that might be used clinically. As a next step evaluation using human dura, macroscopic biomechanical testing, penetration-depth analysis, and safety assessment is warranted.
SN - 1932-6203
ER -