Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair
Appropriate cell sources, bioactive factors and biomaterials for generation of functional and integrated annulus fibrosus (AF) tissue analogues are still an unmet need. In the present study, the AF cell markers, collagen type I, cluster of differentiation 146 (CD146), mohawk (MKX) and smooth muscle...
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AO Research Institute Davos
2020-01-01
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doaj-f118207f18f143acaa937d92bcac2b312020-11-25T01:30:02Zeng AO Research Institute DavosEuropean Cells & Materials1473-22622020-01-013911710.22203/eCM.v039a01Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repairJ DuRG LongT NakaiD SakaiLM BennekerG ZhouB LiD EglinJC IatridisM AliniS GradZ Li0AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos Platz, SwitzerlandAppropriate cell sources, bioactive factors and biomaterials for generation of functional and integrated annulus fibrosus (AF) tissue analogues are still an unmet need. In the present study, the AF cell markers, collagen type I, cluster of differentiation 146 (CD146), mohawk (MKX) and smooth muscle protein 22α (SM22α) were found to be suitable indicators of functional AF cell induction. In vitro 2D culture of human AF cells showed that transforming growth factor β1 (TGF-β1) upregulated the expression of the functional AF markers and increased cell contractility, indicating that TGF-β1-pre-treated AF cells were an appropriate cell source for AF tissue regeneration. Furthermore, a tissue engineered construct, composed of polyurethane (PU) scaffold with a TGF-β1-supplemented collagen type I hydrogel and human AF cells, was evaluated with in vitro 3D culture and ex vivo preclinical bioreactor-loaded organ culture models. The collagen type I hydrogel helped maintaining the AF functional phenotype. TGF-β1 supplement within the collagen I hydrogel further promoted cell proliferation and matrix production of AF cells within in vitro 3D culture. In the ex vivo IVD organ culture model with physiologically relevant mechanical loading, TGF-β1 supplement in the transplanted constructs induced the functional AF cell phenotype and enhanced collagen matrix synthesis. In conclusion, TGF-β1-containing collagen-PU constructs can induce the functional cell phenotype of human AF cells in vitro and in situ. This combined cellular, biomaterial and bioactive agent therapy has a great potential for AF tissue regeneration and rupture repair.https://www.ecmjournal.org/papers/vol039/pdf/v039a01.pdfannulus fibrosusannular rupture repairtissue engineeringtransforming growth factor β1polyurethane scaffold |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
J Du RG Long T Nakai D Sakai LM Benneker G Zhou B Li D Eglin JC Iatridis M Alini S Grad Z Li |
spellingShingle |
J Du RG Long T Nakai D Sakai LM Benneker G Zhou B Li D Eglin JC Iatridis M Alini S Grad Z Li Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair European Cells & Materials annulus fibrosus annular rupture repair tissue engineering transforming growth factor β1 polyurethane scaffold |
author_facet |
J Du RG Long T Nakai D Sakai LM Benneker G Zhou B Li D Eglin JC Iatridis M Alini S Grad Z Li |
author_sort |
J Du |
title |
Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair |
title_short |
Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair |
title_full |
Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair |
title_fullStr |
Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair |
title_full_unstemmed |
Functional cell phenotype induction with TGF-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair |
title_sort |
functional cell phenotype induction with tgf-β1 and collagen-polyurethane scaffold for annulus fibrosus rupture repair |
publisher |
AO Research Institute Davos |
series |
European Cells & Materials |
issn |
1473-2262 |
publishDate |
2020-01-01 |
description |
Appropriate cell sources, bioactive factors and biomaterials for generation of functional and integrated annulus fibrosus (AF) tissue analogues are still an unmet need. In the present study, the AF cell markers, collagen type I, cluster of differentiation 146 (CD146), mohawk (MKX) and smooth muscle protein 22α (SM22α) were found to be suitable indicators of functional AF cell induction. In vitro 2D culture of human AF cells showed that transforming growth factor β1 (TGF-β1) upregulated the expression of the functional AF markers and increased cell contractility, indicating that TGF-β1-pre-treated AF cells were an appropriate cell source for AF tissue regeneration. Furthermore, a tissue engineered construct, composed of polyurethane (PU) scaffold with a TGF-β1-supplemented collagen type I hydrogel and human AF cells, was evaluated with in vitro 3D culture and ex vivo preclinical bioreactor-loaded organ culture models. The collagen type I hydrogel helped maintaining the AF functional phenotype. TGF-β1 supplement within the collagen I hydrogel further promoted cell proliferation and matrix production of AF cells within in vitro 3D culture. In the ex vivo IVD organ culture model with physiologically relevant mechanical loading, TGF-β1 supplement in the transplanted constructs induced the functional AF cell phenotype and enhanced collagen matrix synthesis. In conclusion, TGF-β1-containing collagen-PU constructs can induce the functional cell phenotype of human AF cells in vitro and in situ. This combined cellular, biomaterial and bioactive agent therapy has a great potential for AF tissue regeneration and rupture repair. |
topic |
annulus fibrosus annular rupture repair tissue engineering transforming growth factor β1 polyurethane scaffold |
url |
https://www.ecmjournal.org/papers/vol039/pdf/v039a01.pdf |
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