Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.

<h4>Background</h4>Collagen cross-links contribute to the mechanical resilience of the intervertebral disc (IVD). UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) is a well-established and effective ophthalmological intervention that increases the mechanical rigidit...

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Autores principales:	Ioannis Vasilikos, Graciosa Q Teixeira, Andreas Seitz, Julia Nothelfer, Julian Haas, Hans-Joachim Wilke, Boris Mizaikoff, Jürgen Beck, Ulrich Hubbe, Cornelia Neidlinger-Wilke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6355eb61a44b49e3800ffe984bf24257
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spelling	oai:doaj.org-article:6355eb61a44b49e3800ffe984bf242572021-12-02T20:11:04ZCan UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.1932-620310.1371/journal.pone.0252672https://doaj.org/article/6355eb61a44b49e3800ffe984bf242572021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252672https://doaj.org/toc/1932-6203<h4>Background</h4>Collagen cross-links contribute to the mechanical resilience of the intervertebral disc (IVD). UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) is a well-established and effective ophthalmological intervention that increases the mechanical rigidity of the collagen-rich corneal matrix in Keratoconus. This study explores the feasibility, safety and efficacy of translating this intervention in reinforcing the IVD.<h4>Methods</h4>Annulus fibrosus (AF) cells were isolated from bovine IVDs and treated with different combinations of riboflavin (RF) concentrations (0.05-8 mM) and UVA light intensities (0.3-4 mW/cm2). Metabolic activity (resazurin assay), cell viability (TUNEL assay), and gene expression of apoptosis regulators C-FOS and PT5 were assessed immediately and 24 hours after treatment. Biomechanical effects of UVA-CXL on IVDs were measured by indentation analysis of changes in the instantaneous modulus and by peel-force delamination strength analysis of the AF prior and after treatment.<h4>Results</h4>Different intensities of UVA did not impair the metabolic activity of AF cells. However, RF affected metabolic activity (p < 0.001). PT53 expression was similar in all RF conditions tested while C-FOS expression decreased 24 hours after treatment. Twenty-four hours after treatment, no apoptotic cells were observed in any condition tested. Biomechanical characterizations showed a significant increase in the annular peel strength of the UVA-CXL group, when compared to controls of UVA and RF alone (p < 0.05). UVA-CXL treated IVDs showed up to 152% higher (p < 0.001) instantaneous modulus values compared to the untreated control.<h4>Conclusion</h4>This is the first study on UVA-CXL treatment of IVD. It induced significantly increased delamination strength and instantaneous modulus indentation values in intact IVD samples in a structure-function relationship. RF concentrations and UVA intensities utilized in ophthalmological clinical protocols were well tolerated by the AF cells. Our findings suggest that UVA-CXL may be a promising tool to reinforce the IVD matrix.Ioannis VasilikosGraciosa Q TeixeiraAndreas SeitzJulia NothelferJulian HaasHans-Joachim WilkeBoris MizaikoffJürgen BeckUlrich HubbeCornelia Neidlinger-WilkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252672 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ioannis Vasilikos Graciosa Q Teixeira Andreas Seitz Julia Nothelfer Julian Haas Hans-Joachim Wilke Boris Mizaikoff Jürgen Beck Ulrich Hubbe Cornelia Neidlinger-Wilke Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.
description	<h4>Background</h4>Collagen cross-links contribute to the mechanical resilience of the intervertebral disc (IVD). UVA-light-activated riboflavin-induced collagen crosslinking (UVA-CXL) is a well-established and effective ophthalmological intervention that increases the mechanical rigidity of the collagen-rich corneal matrix in Keratoconus. This study explores the feasibility, safety and efficacy of translating this intervention in reinforcing the IVD.<h4>Methods</h4>Annulus fibrosus (AF) cells were isolated from bovine IVDs and treated with different combinations of riboflavin (RF) concentrations (0.05-8 mM) and UVA light intensities (0.3-4 mW/cm2). Metabolic activity (resazurin assay), cell viability (TUNEL assay), and gene expression of apoptosis regulators C-FOS and PT5 were assessed immediately and 24 hours after treatment. Biomechanical effects of UVA-CXL on IVDs were measured by indentation analysis of changes in the instantaneous modulus and by peel-force delamination strength analysis of the AF prior and after treatment.<h4>Results</h4>Different intensities of UVA did not impair the metabolic activity of AF cells. However, RF affected metabolic activity (p < 0.001). PT53 expression was similar in all RF conditions tested while C-FOS expression decreased 24 hours after treatment. Twenty-four hours after treatment, no apoptotic cells were observed in any condition tested. Biomechanical characterizations showed a significant increase in the annular peel strength of the UVA-CXL group, when compared to controls of UVA and RF alone (p < 0.05). UVA-CXL treated IVDs showed up to 152% higher (p < 0.001) instantaneous modulus values compared to the untreated control.<h4>Conclusion</h4>This is the first study on UVA-CXL treatment of IVD. It induced significantly increased delamination strength and instantaneous modulus indentation values in intact IVD samples in a structure-function relationship. RF concentrations and UVA intensities utilized in ophthalmological clinical protocols were well tolerated by the AF cells. Our findings suggest that UVA-CXL may be a promising tool to reinforce the IVD matrix.
format	article
author	Ioannis Vasilikos Graciosa Q Teixeira Andreas Seitz Julia Nothelfer Julian Haas Hans-Joachim Wilke Boris Mizaikoff Jürgen Beck Ulrich Hubbe Cornelia Neidlinger-Wilke
author_facet	Ioannis Vasilikos Graciosa Q Teixeira Andreas Seitz Julia Nothelfer Julian Haas Hans-Joachim Wilke Boris Mizaikoff Jürgen Beck Ulrich Hubbe Cornelia Neidlinger-Wilke
author_sort	Ioannis Vasilikos
title	Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.
title_short	Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.
title_full	Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.
title_fullStr	Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.
title_full_unstemmed	Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.
title_sort	can uva-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? a feasibility study on bovine intervertebral disc.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6355eb61a44b49e3800ffe984bf24257
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Can UVA-light-activated riboflavin-induced collagen crosslinking be transferred from ophthalmology to spine surgery? A feasibility study on bovine intervertebral disc.

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